In findings that advance scientists' understanding of a whole class of inherited disorders, a team from The Scripps Research Institute has shed light on a mechanism that enables a potential treatment for Gaucher's disease and other lysosomal storage diseases.
The findings were published in an advance, online edition of the journal Nature Chemical Biology on May 9, 2010.
"This study is likely to motivate clinical trials for the treatment of neuropathic lysosomal storage diseases, including Gaucher's disease, where the current standard of care, enzyme replacement therapy, is ineffective," said team leader Jeffery Kelly, who is chair of the Scripps Research Department of Molecular and Experimental Medicine, Lita Annenberg Hazen Professor of Chemistry, and a member of the Skaggs Institute of Chemical Biology. "The research is especially promising because we enhanced the cellular folding and function of mutated lysosomal enzymes, whose deficient function is linked to lysosomal storage diseases, using two distinct categories of FDA-approved drugs that have been shown to be safe and effective for the treatment of high blood pressure and muscle spasms."
"We wanted to uncover general principles that could be applied to a variety of loss-of-function protein misfolding diseases," added Derrick Sek Tong Ong, a graduate student in the Scripps Research Kellogg School of Science and Technology who was first author of the paper. "This study reveals how we can enhance the capacity of the cellular machinery to fold and traffic a mutant enzyme, so that the protein can function better."
In the new paper, the team revealed how the widely available prescription drugs diltiazem, verapamil, and in some cases dantrolene, acted on cells from patients with Gaucher's disease, increasing calcium levels in a subcellular compartment called the endoplasmic reticulum - a convoluted membranous sac within the cell where the folding of many proteins takes place.
A Genetic Disease
Gaucher's disease is the most common genetic disease among the Ashkenazi Jewish population of Eastern European ancestry. Symptoms include bruising easily due to low blood platelets, enlargement of the liver and spleen, and fatigue due to anemia. The disease also causes cells in the bone marrow to become engorged with a fatty storage material, which may lead to bone lesions, weakening the skeleton, sometimes resulting in painful fractures. In some instances, the disease also impairs the function of the lungs or the central nervous system.
Gaucher's disease (named after the French dermatologist Phillipe Gaucher, who first described the condition in 1882) is caused by mutations in a person's beta-glucosidase genes, and these defects corrupt his or her beta-glucosidase enzyme. Some of these corrupted enzymes cannot fold properly into their correct three-dimensional structure because they are unstable in the neutral pH environment of the endoplasmic reticulum. The corrupted, mutant enzymes are often degraded by a process known as endoplasmic reticulum-associated degradation, and fail to reach their destination - another subcellular compartment called the lysosome, where they normally break down a fatty substance called glucosylceramides. When the beta-glucosidase concentration and/or enzymatic activity in the lysosome are too low, glucosylceramides accumulate, causing the symptoms of Gaucher's disease.
The current approaches for treating Gaucher's disease (and a few of the 40 or so other lysosomal storage disorders) involve replacing the deficient enzyme with an enzyme that is made using recombinant engineering and then is injected into the patient. Enzyme replacement therapy is an effective way to restore many patients to good health, but it has drawbacks. The enzyme has to be infused intravenously or through a surgically implanted catheter - usually in a doctor's office - a process that takes several hours and must be repeated every one or two weeks. Enzyme replacement therapy is also expensive, costing between $100,000 and $750,000 per year per patient. And this therapy is not effective at treating neurological complications of lysosomal storage diseases because injected enzymes cannot enter the brain.
However, a series of papers from the Kelly lab has shown that several other treatment approaches hold promise.
The Promise of a New Treatment Approach
In a paper published in PLoS Biology in 2008, the lab found that the prescription drugs diltiazem and verapamil were effective in restoring partial cellular folding, trafficking, and function to mutant enzymes responsible for three lysosomal storage disorders, including Gaucher's disease.
The scientists suspected that the drugs enhanced the interaction between the mutant lysosomal enzyme and the machinery of the cell that folds proteins, the so-called "chaperones" (helper proteins). Enhanced chaperone function, the scientists believed, might enhance the extent of mutant enzyme folding in the endoplasmic reticulum, allowing more of the mutant enzymes to engage the trafficking pathway that transports them to the lysosome. Even though the mutant enzymes are not completely normal, they exhibit sufficient function (greater than 10 percent) to improve the lysosomal storage phenomenon that causes these maladies.
But to make a more persuasive case for expensive clinical trials, the scientists wanted to understand the mechanism(s) by which the drugs were altering the cellular chaperones. The new study helps answer this question.
Using biochemical, pharmacologic, and siRNA techniques, the scientists examined the hypothesis that these drugs increased calcium levels in the endoplasmic reticulum post-translationally enhancing the calcium-regulated chaperones.
"We interrogated the importance of two calcium efflux channels and one pump (SERCA) on endoplasmic reticulum calcium levels," said Ong. "We found that one of the calcium efflux channels was sufficient to increase calcium levels - the ryanodine receptor."
These drugs appear to enhance the function of a chaperone called calnexin, which is expected to aid the folding of most lysosomal enzymes because of their common biochemistry (post-translational modification-N-linked glycosylation).
While Ong is hopeful that the drugs will be effective for treating Gaucher's disease and other lysosomal storage disorders, he also cautions that many steps still need to be taken before such treatment is approved for use in patients.
"We are always cautious because what works in patient-derived cells does not always work in humans," he said.
In addition to Kelly and Ong, authors of the paper "Endoplasmic reticulum Ca2+ increases enhance mutant glucocerebrosidase proteostasis" are Ting-Wei Mu of Scripps Research and Amy E. Palmer of the University of Colorado, Boulder.
This work was supported by the National Institutes of Health, the Skaggs Institute for Chemical Biology, and the Lita Annenberg Hazen Foundation.
Source:
Keith McKeown
Scripps Research Institute
View drug information on Diltiazem HCL, Extended-Release Capsules; Verapamil.
вторник, 26 апреля 2011 г.
FDA Approves RiaSTAP For Treatment Of Bleeding In Patients With Rare Genetic Defect
The U.S. Food and Drug Administration licensed RiaSTAP, an orphan drug for the treatment of bleeding in patients with a rare genetic defect known as congenital fibrinogen deficiency. Without treatment, these patients are at risk of potentially life-threatening bleeding.
People with congenital fibrinogen deficiency are unable to make sufficient amounts of fibrinogen, which plays an important role in blood coagulation by helping to form blood clots and prevent bleeding. Fibrinogen is manufactured in the liver and circulates in the blood plasma in a normal concentration of 250-400 mg/dL.
"This product offers much-needed treatment for the small number of patients with congenital fibrinogen deficiency," said Jesse Goodman, M.D., M.P.H., director of the FDA's Center for Biologics Evaluation and Research. "If bleeding occurs in the brain or other organs and is left untreated, it may lead to blood loss, organ damage and death."
Fibrinogen deficiency affects only 150 to 300 people in the United States and is usually diagnosed at birth when newborns bleed from their umbilical cord site. Children with the defect need to curtail activities because of risk of bleeding from minor trauma.
RiaSTAP is an intravenous fibrinogen concentrate made from the plasma of healthy human blood donors. The product is indicated for patients who have no fibrinogen or low levels of the substance, an abnormality known as afibrinogenemia, or for those patients whose fibrinogen levels are below 50 mg/dL, an abnormality known as hypofibrinogememia. The product is not indicated for patients with dysfibrinogenemia, who may have normal fibrinogen levels but defective fibrinogen function. Patients such as these are at risk for both bleeding and clotting complications.
The licensing of RiaSTAP was supported by a study of 15 patients with afibrinogenemia who achieved the target level of fibrinogen expected to prevent bleeding after they received 70 mg/kg of the drug. In addition, plasma from 14 of the 15 patients showed increased maximum clot firmness, a surrogate marker likely to predict clinical benefit. Fever and headache were the most common adverse reactions.
Clinical benefit will be further verified in a postmarketing study which will include both afibrinogenemic and hypofibrinogenemic patients.
Orphan drugs are drugs or biologics intended for use in a rare disease or condition. Manufacturers are qualified to receive certain government benefits in exchange for developing such products. RiaSTAP [Fibrinogen Concentrate (Human)] was developed under the FDA's accelerated approval regulations.
The drug is manufactured by CSL Behring, Marburg, Germany.
U.S. Food and Drug Administration
People with congenital fibrinogen deficiency are unable to make sufficient amounts of fibrinogen, which plays an important role in blood coagulation by helping to form blood clots and prevent bleeding. Fibrinogen is manufactured in the liver and circulates in the blood plasma in a normal concentration of 250-400 mg/dL.
"This product offers much-needed treatment for the small number of patients with congenital fibrinogen deficiency," said Jesse Goodman, M.D., M.P.H., director of the FDA's Center for Biologics Evaluation and Research. "If bleeding occurs in the brain or other organs and is left untreated, it may lead to blood loss, organ damage and death."
Fibrinogen deficiency affects only 150 to 300 people in the United States and is usually diagnosed at birth when newborns bleed from their umbilical cord site. Children with the defect need to curtail activities because of risk of bleeding from minor trauma.
RiaSTAP is an intravenous fibrinogen concentrate made from the plasma of healthy human blood donors. The product is indicated for patients who have no fibrinogen or low levels of the substance, an abnormality known as afibrinogenemia, or for those patients whose fibrinogen levels are below 50 mg/dL, an abnormality known as hypofibrinogememia. The product is not indicated for patients with dysfibrinogenemia, who may have normal fibrinogen levels but defective fibrinogen function. Patients such as these are at risk for both bleeding and clotting complications.
The licensing of RiaSTAP was supported by a study of 15 patients with afibrinogenemia who achieved the target level of fibrinogen expected to prevent bleeding after they received 70 mg/kg of the drug. In addition, plasma from 14 of the 15 patients showed increased maximum clot firmness, a surrogate marker likely to predict clinical benefit. Fever and headache were the most common adverse reactions.
Clinical benefit will be further verified in a postmarketing study which will include both afibrinogenemic and hypofibrinogenemic patients.
Orphan drugs are drugs or biologics intended for use in a rare disease or condition. Manufacturers are qualified to receive certain government benefits in exchange for developing such products. RiaSTAP [Fibrinogen Concentrate (Human)] was developed under the FDA's accelerated approval regulations.
The drug is manufactured by CSL Behring, Marburg, Germany.
U.S. Food and Drug Administration
New Guidelines To Help Diagnose Bleeding Disorders
Nearly one percent of the population suffers from bleeding disorders, yet many women don't know they have one because doctors aren't looking for the condition, according to researchers at Duke University Medical Center.
That's about to change, now that an international expert consortium specifically outlined the definitive signs that may signal the presence of a bleeding disorder in women. The consortium's recommendations are published online and will appear in the July issue of the American Journal of Obstetrics and Gynecology.
The new guidelines aren't just for doctors. Women who suffer from heavy menstrual cycles should be on the lookout for these signs as well, says Andra James, MD, a Duke obstetrician, who says about 25 percent of women with heavy menstruation may have an undiagnosed bleeding disorder.
"Heavy bleeding should not be ignored," says James, the paper's lead author. "When a woman's blood can't clot normally the most obvious sign is a heavy period."
Yet when faced with these scenarios, most doctors aren't suspecting a blood clotting problem is to blame. "Sometimes they think hormones are the cause, or fibroids," says James. "In some cases they recommend removal of the uterus or offer another gynecologic explanation when the real contributing factor is a blood clotting disorder."
In previous studies, women who ultimately were treated for a bleeding disorder reported waiting 16 years, on average, before being diagnosed. In extreme cases, James says undiagnosed bleeding disorders have led to women bleeding to death during menstruation, childbirth and surgical procedures.
The most common inherited bleeding disorder is von Willebrand disease, says James, author of 100 Questions and Answers About von Willebrand Disease (Jones and Bartlett). Common criteria for diagnosis include the presence of a family history of bleeding, personal history of bleeding and laboratory tests that indicate the lack of a protein called von Willebrand factor which is essential for clotting.
Without the laboratory test, the consortium says women and doctors should be on the lookout for the following:
Heavy blood loss during menstruation
Family history of bleeding disorder
Notable bruising without injury
Minor wound bleeding that lasts more than five minutes
Prolonged or excessive bleeding following dental extraction
Unexpected surgical bleeding
Hemorrhaging that requires blood transfusion
Postpartum hemorrhaging, especially if occurs more than 24 hours after delivery.
"Too often women think heavy bleeding is okay because the women in their family -- who may also have an undiagnosed bleeding disorder -- have heavy periods as well," says James. "We want women who continually experience abnormal reproductive tract bleeding, specifically heavy menstrual bleeding, to be alert to these other signs and approach their physicians about being evaluated."
In addition, she says doctors should be asking the right questions and ordering appropriate laboratory tests in suspected patients.
"Not every patient who has abnormal reproductive tract bleeding has a bleeding disorder, and most don't," James says. "But since up to one-quarter do, this needs to be recognized. Once treated, these women can expect to have normal periods and go through childbirth safely."
The consortium's meeting received financial support from CSL Behring.
Source:
Debbe Geiger
Duke University Medical Center
That's about to change, now that an international expert consortium specifically outlined the definitive signs that may signal the presence of a bleeding disorder in women. The consortium's recommendations are published online and will appear in the July issue of the American Journal of Obstetrics and Gynecology.
The new guidelines aren't just for doctors. Women who suffer from heavy menstrual cycles should be on the lookout for these signs as well, says Andra James, MD, a Duke obstetrician, who says about 25 percent of women with heavy menstruation may have an undiagnosed bleeding disorder.
"Heavy bleeding should not be ignored," says James, the paper's lead author. "When a woman's blood can't clot normally the most obvious sign is a heavy period."
Yet when faced with these scenarios, most doctors aren't suspecting a blood clotting problem is to blame. "Sometimes they think hormones are the cause, or fibroids," says James. "In some cases they recommend removal of the uterus or offer another gynecologic explanation when the real contributing factor is a blood clotting disorder."
In previous studies, women who ultimately were treated for a bleeding disorder reported waiting 16 years, on average, before being diagnosed. In extreme cases, James says undiagnosed bleeding disorders have led to women bleeding to death during menstruation, childbirth and surgical procedures.
The most common inherited bleeding disorder is von Willebrand disease, says James, author of 100 Questions and Answers About von Willebrand Disease (Jones and Bartlett). Common criteria for diagnosis include the presence of a family history of bleeding, personal history of bleeding and laboratory tests that indicate the lack of a protein called von Willebrand factor which is essential for clotting.
Without the laboratory test, the consortium says women and doctors should be on the lookout for the following:
Heavy blood loss during menstruation
Family history of bleeding disorder
Notable bruising without injury
Minor wound bleeding that lasts more than five minutes
Prolonged or excessive bleeding following dental extraction
Unexpected surgical bleeding
Hemorrhaging that requires blood transfusion
Postpartum hemorrhaging, especially if occurs more than 24 hours after delivery.
"Too often women think heavy bleeding is okay because the women in their family -- who may also have an undiagnosed bleeding disorder -- have heavy periods as well," says James. "We want women who continually experience abnormal reproductive tract bleeding, specifically heavy menstrual bleeding, to be alert to these other signs and approach their physicians about being evaluated."
In addition, she says doctors should be asking the right questions and ordering appropriate laboratory tests in suspected patients.
"Not every patient who has abnormal reproductive tract bleeding has a bleeding disorder, and most don't," James says. "But since up to one-quarter do, this needs to be recognized. Once treated, these women can expect to have normal periods and go through childbirth safely."
The consortium's meeting received financial support from CSL Behring.
Source:
Debbe Geiger
Duke University Medical Center
Harnessing The Natural Healing Process
Immunological research at the University of Haifa, Israel, has made a new breakthrough, revealing a critical component in the "decision-making" process of white blood cells that play a role in the healing process from bacterial inflammation. "The process that we have discovered can assist in the development of drugs that are based on the natural processes that take place in the human body, unlike most of the existing drugs that attempt to curb inflammation by artificial means," explains Dr. Amiram Ariel of the Department of Biology at the University of Haifa, who headed the study. The research and its results have been published in the scientific journal European Journal of Immunology.
Bacterial inflammation forms in the body when bacteria (pathogens) penetrate body tissue. In response, specific types of white blood cells (neutrophils) begin to fight the invaders, to destroy and remove them from the tissue. In normal conditions, inflammation is terminated once the cells have managed to eradicate the bacteria and then undergo programmed cell death. At that point, another type of white blood cells come on stage - macrophages - whose job it is to take up the dead cells (the neutrophils) and to restore the tissue to its normal functioning state. While the macrophages feast on their cell meal, they gain the ability to begin the tissue's rehabilitation process. However, at one point they abandon the tissue and make their way over to immune system organs, via the lymphatic system, where they deliver the "back to routine" message to the rest of the immune system. This message is important for the body's return to normal functioning. Until now, however, the when and how that directs macrophages' leaving the inflamed tissue remained unknown.
Dr. Ariel explains that even when the body manages to cope with the bacterial invaders, there is also the danger of "excessive" healing that will result in fibrosis and scar formation. This happens when the system reels out of control and "over-heals" the previously infected area. Fibrosis can lead to malfunctioning of the healing tissue, tissue death and sometimes even mortality. To understand why this happens, it is important to identify and understand the way macrophages' govern the healing process.
The current study, conducted by Dr. Ariel alongside a team of students led by Dr. Sagie Schif-Zuck, set out to probe the critical stage of the healing process, when the macrophages decide to relocate and adjust their healing activities, moving from local rehabilitation of the damaged tissue to shut down of systemic immune responses at organs of the immune system.
The researchers discovered that the macrophages have a fascinating "uptake threshold" of seven cells. After engulfing seven neutrophils they are "licensed" to leave the tissue and continue with their remote tasks. The research also found that these cells are sensitive to the tissue's healing pace, so that when the tissue is healing quicker, they are permitted to leave earlier, and when the tissue is finding it harder to repair itself, they hang around longer, even after reaching the uptake threshold of seven cells. The researchers also discovered substances that "inform" the cells on the tissue's rate of repair, and found that by injecting these substances, the macrophages' transition to immune organs is accelerated while new macrophages are recruited to further treat the damaged tissue and continue the healing process. In addition, the study revealed that as they leave the tissue, the macrophages undergo molecular changes necessary to carry out their new functions in the lymphatic system.
"Our new study has found a major event in the inflammatory healing process that is responsible for the transition of macrophages from local rehabilitation of the damaged tissue to its consequent role in promoting the immune system's return to routine. The findings from our study can assist in the development of biological drugs that are based on the body's natural processes and biomolecules. Today, most drugs are designed to block particular pathways in the inflammatory process, which is also a "fight back" strategy found in bacteria and viruses; but in many cases, the body relates to such a drug as a type of 'bacterial invasion', finds ways to circumvent it and produces an alternative immunological response to the blocked one. By harnessing the natural healing process that we have discovered, the body will be able to naturally complete and terminate all the inflammatory processes, and will be able to avoid the deficiencies of existing anti-inflammatory treatments," Dr. Ariel concludes.
Source:
Rachel Feldman
University of Haifa
Bacterial inflammation forms in the body when bacteria (pathogens) penetrate body tissue. In response, specific types of white blood cells (neutrophils) begin to fight the invaders, to destroy and remove them from the tissue. In normal conditions, inflammation is terminated once the cells have managed to eradicate the bacteria and then undergo programmed cell death. At that point, another type of white blood cells come on stage - macrophages - whose job it is to take up the dead cells (the neutrophils) and to restore the tissue to its normal functioning state. While the macrophages feast on their cell meal, they gain the ability to begin the tissue's rehabilitation process. However, at one point they abandon the tissue and make their way over to immune system organs, via the lymphatic system, where they deliver the "back to routine" message to the rest of the immune system. This message is important for the body's return to normal functioning. Until now, however, the when and how that directs macrophages' leaving the inflamed tissue remained unknown.
Dr. Ariel explains that even when the body manages to cope with the bacterial invaders, there is also the danger of "excessive" healing that will result in fibrosis and scar formation. This happens when the system reels out of control and "over-heals" the previously infected area. Fibrosis can lead to malfunctioning of the healing tissue, tissue death and sometimes even mortality. To understand why this happens, it is important to identify and understand the way macrophages' govern the healing process.
The current study, conducted by Dr. Ariel alongside a team of students led by Dr. Sagie Schif-Zuck, set out to probe the critical stage of the healing process, when the macrophages decide to relocate and adjust their healing activities, moving from local rehabilitation of the damaged tissue to shut down of systemic immune responses at organs of the immune system.
The researchers discovered that the macrophages have a fascinating "uptake threshold" of seven cells. After engulfing seven neutrophils they are "licensed" to leave the tissue and continue with their remote tasks. The research also found that these cells are sensitive to the tissue's healing pace, so that when the tissue is healing quicker, they are permitted to leave earlier, and when the tissue is finding it harder to repair itself, they hang around longer, even after reaching the uptake threshold of seven cells. The researchers also discovered substances that "inform" the cells on the tissue's rate of repair, and found that by injecting these substances, the macrophages' transition to immune organs is accelerated while new macrophages are recruited to further treat the damaged tissue and continue the healing process. In addition, the study revealed that as they leave the tissue, the macrophages undergo molecular changes necessary to carry out their new functions in the lymphatic system.
"Our new study has found a major event in the inflammatory healing process that is responsible for the transition of macrophages from local rehabilitation of the damaged tissue to its consequent role in promoting the immune system's return to routine. The findings from our study can assist in the development of biological drugs that are based on the body's natural processes and biomolecules. Today, most drugs are designed to block particular pathways in the inflammatory process, which is also a "fight back" strategy found in bacteria and viruses; but in many cases, the body relates to such a drug as a type of 'bacterial invasion', finds ways to circumvent it and produces an alternative immunological response to the blocked one. By harnessing the natural healing process that we have discovered, the body will be able to naturally complete and terminate all the inflammatory processes, and will be able to avoid the deficiencies of existing anti-inflammatory treatments," Dr. Ariel concludes.
Source:
Rachel Feldman
University of Haifa
Retacrit(R) Data Confirm Equivalent Efficacy To Epoetin Alfa In Renal Anaemia
Hospira (NYSE: HSP), the world leader in generic injectable pharmaceuticals, today presented new data showing Retacrit® (epoetin zeta) corrects low haemoglobin (Hb) levels as effectively and rapidly as epoetin alfa (Erypo®) in patients with chronic kidney disease (CKD).1 Other data also presented at the joint European Dialysis and Transplant Nurses Association/European Renal Care Association (EDTNA/ERCA) conference show Retacrit has equivalent efficacy to epoetin alfa in reducing the need for blood transfusions2 and is effective in maintaining target Hb levels in adult patients.3
Principal investigator of all three analyses, Professor Paul Scigalla of International Clinical Research Consulting (ICRC), commented, "These new data give further evidence that Retacrit provides a viable alternative to epoetin alfa in the treatment of anaemia associated with chronic kidney disease, offering equivalent clinical benefits and greater cost-effectiveness".
Analyses were presented from two randomised, double-blind Phase III trials involving 609 patients (305 receiving Retacrit) in the correction phase study4 and 313 patients (300 receiving Retacrit) in the crossover maintenance phase study.5
In the analysis of time to Hb response (based on data from the correction phase study), treatment efficacy was similar in Retacrit and epoetin alfa treatment arms (84% of patients achieved a Hb response on Retacrit versus 86% on epoetin alfa). The average time to Hb response was also equivalent in both study arms (12.5 weeks for patients on Retacrit, and 12.1 weeks for those on epoetin alfa).1
Additionally, the analysis of transfusion requirements showed a similar transfusion requirement in the two treatment groups in both the correction and maintenance phase studies. In the correction phase study, 96.3% of patients in the Retacrit-treated group and 95.1% of patients in the epoetin alfa-treated group did not require any blood transfusions during treatment. In the maintenance phase study, three patients in the group receiving Retacrit and two in the group receiving epoetin alfa required blood transfusions.2
Finally, the effectiveness of Retacrit in maintaining Hb levels in patients with renal anaemia was analysed by age: 81 patients aged over 65 years were compared with 232 patients aged up to and including 65 years. In both the younger age group (≤65) and older age group (>65), Retacrit was effective in maintaining target Hb levels. The mean Hb levels in the younger group were 11.4 g/dL for Retacrit-treated patients and 11.6 g/dL for epoetin alfa-treated patients. In the over-65 age group, mean Hb levels were 11.3 g/dL for patients receiving Retacrit and 11.5 g/dL for patients receiving epoetin alfa. Further, no significant differences were seen between the mean dose of each drug administered in both age groups.3
"Hospira is pleased to present these new Retacrit data, which confirm a commitment to develop, manufacture and market biosimilars in order to meet future demand for cost-effective alternatives to proprietary biopharmaceuticals" said Islah Ahmed, Medical Director, Global Medical Affairs, Hospira.
About the analyses
Time to haemoglobin response analysis: 609 patients (18��"75 years old) with CKD maintained on haemodialysis and with anaemia (Hb 65 years and ≤65 years: Data from the maintenance phase study was analysed to assess efficacy in maintaining Hb levels according to age: the 81 patients aged over 65 being compared with the 232 patients aged up to and including 65 years.
About Retacrit
Retacrit is a biosimilar erythropoietin approved in Europe6 for the treatment of anaemia associated with chronic kidney disease (administered intravenously) and chemotherapy (administered subcutaneously). Approval was granted on the basis of strong safety and efficacy data, as well as compliance with extensive quality, clinical and non-clinical guidelines. Retacrit has been launched in several European countries including Germany, Austria, the UK, Ireland, Greece, Sweden, Norway and Portugal, and is manufactured and packaged in Germany using advanced technology and following Good Manufacturing Practice (GMP) standards.
About Hospira
Hospira is a global specialty pharmaceutical and medication delivery company dedicated to Advancing Wellness™. As the world leader in specialty generic injectable pharmaceuticals, Hospira offers one of the broadest portfolios of generic acute-care and oncology injectables, as well as integrated infusion therapy and medication management solutions. Through its products, Hospira helps improve the safety, cost and productivity of patient care. The company is headquartered in Lake Forest, Illinois, United States, and has more than 14,000 employees. The head office for Hospira in Europe, Middle East and Africa is in Leamington Spa, UK. Learn more about Hospira at hospira
References
1. Scigalla P, Koytchev R. Time to haemoglobin response with epoetin zeta compared with epoetin alfa in patients with renal anaemia. Presented at European Dialysis and Transplant Nurses Association/European Renal Care Association conference (EDTNA/ERCA), Prague, Czech Republic 6-9 September 2008. Abstract P07.
2. Scigalla P, Koytchev R. Reduction of transfusion requirements with epoetin zeta in patients with renal anaemia. Presented at European Dialysis and Transplant Nurses Association/European Renal Care Association conference (EDTNA/ERCA), Prague, Czech Republic 6-9 September 2008. Abstract P05.
3. Scigalla P, Koytchev R. Efficacy of epoetin zeta in renal anaemia: comparing patients aged >65 years and ≤ 65 years. Presented at European Dialysis and Transplant Nurses Association/European Renal Care Association conference (EDTNA/ERCA), Prague, Czech Republic 6-9 September 2008. Abstract P06.
4. Krivoshiev S, Todorov VV, Manitius J, Czekalski S, Scigalla P and Koytchev R on behalf of the Epoetin Zeta Study Group. Comparison of the therapeutic effects of epoetin zeta and epoetin alfa in the correction of renal anaemia. Curr Med Res Opin 2008; 24(5): 1407-1415.
5. Wizemann V, Rutkowski B, Baldamus C et al. Comparison of the therapeutic effects of epoetin zeta to epoetin alfa in the maintenance phase of renal anaemia treatment [published erratum in Curr Med Res Opin 2008; 24(4): 1155]. Curr Med Res Opin 2008; 24(3): 625-637.
6. European Medicines Agency (EMEA) European Public Assessment Report: Retacrit®. Available at emea.europa.eu. Accessed September 2008.
Hospira
Principal investigator of all three analyses, Professor Paul Scigalla of International Clinical Research Consulting (ICRC), commented, "These new data give further evidence that Retacrit provides a viable alternative to epoetin alfa in the treatment of anaemia associated with chronic kidney disease, offering equivalent clinical benefits and greater cost-effectiveness".
Analyses were presented from two randomised, double-blind Phase III trials involving 609 patients (305 receiving Retacrit) in the correction phase study4 and 313 patients (300 receiving Retacrit) in the crossover maintenance phase study.5
In the analysis of time to Hb response (based on data from the correction phase study), treatment efficacy was similar in Retacrit and epoetin alfa treatment arms (84% of patients achieved a Hb response on Retacrit versus 86% on epoetin alfa). The average time to Hb response was also equivalent in both study arms (12.5 weeks for patients on Retacrit, and 12.1 weeks for those on epoetin alfa).1
Additionally, the analysis of transfusion requirements showed a similar transfusion requirement in the two treatment groups in both the correction and maintenance phase studies. In the correction phase study, 96.3% of patients in the Retacrit-treated group and 95.1% of patients in the epoetin alfa-treated group did not require any blood transfusions during treatment. In the maintenance phase study, three patients in the group receiving Retacrit and two in the group receiving epoetin alfa required blood transfusions.2
Finally, the effectiveness of Retacrit in maintaining Hb levels in patients with renal anaemia was analysed by age: 81 patients aged over 65 years were compared with 232 patients aged up to and including 65 years. In both the younger age group (≤65) and older age group (>65), Retacrit was effective in maintaining target Hb levels. The mean Hb levels in the younger group were 11.4 g/dL for Retacrit-treated patients and 11.6 g/dL for epoetin alfa-treated patients. In the over-65 age group, mean Hb levels were 11.3 g/dL for patients receiving Retacrit and 11.5 g/dL for patients receiving epoetin alfa. Further, no significant differences were seen between the mean dose of each drug administered in both age groups.3
"Hospira is pleased to present these new Retacrit data, which confirm a commitment to develop, manufacture and market biosimilars in order to meet future demand for cost-effective alternatives to proprietary biopharmaceuticals" said Islah Ahmed, Medical Director, Global Medical Affairs, Hospira.
About the analyses
Time to haemoglobin response analysis: 609 patients (18��"75 years old) with CKD maintained on haemodialysis and with anaemia (Hb 65 years and ≤65 years: Data from the maintenance phase study was analysed to assess efficacy in maintaining Hb levels according to age: the 81 patients aged over 65 being compared with the 232 patients aged up to and including 65 years.
About Retacrit
Retacrit is a biosimilar erythropoietin approved in Europe6 for the treatment of anaemia associated with chronic kidney disease (administered intravenously) and chemotherapy (administered subcutaneously). Approval was granted on the basis of strong safety and efficacy data, as well as compliance with extensive quality, clinical and non-clinical guidelines. Retacrit has been launched in several European countries including Germany, Austria, the UK, Ireland, Greece, Sweden, Norway and Portugal, and is manufactured and packaged in Germany using advanced technology and following Good Manufacturing Practice (GMP) standards.
About Hospira
Hospira is a global specialty pharmaceutical and medication delivery company dedicated to Advancing Wellness™. As the world leader in specialty generic injectable pharmaceuticals, Hospira offers one of the broadest portfolios of generic acute-care and oncology injectables, as well as integrated infusion therapy and medication management solutions. Through its products, Hospira helps improve the safety, cost and productivity of patient care. The company is headquartered in Lake Forest, Illinois, United States, and has more than 14,000 employees. The head office for Hospira in Europe, Middle East and Africa is in Leamington Spa, UK. Learn more about Hospira at hospira
References
1. Scigalla P, Koytchev R. Time to haemoglobin response with epoetin zeta compared with epoetin alfa in patients with renal anaemia. Presented at European Dialysis and Transplant Nurses Association/European Renal Care Association conference (EDTNA/ERCA), Prague, Czech Republic 6-9 September 2008. Abstract P07.
2. Scigalla P, Koytchev R. Reduction of transfusion requirements with epoetin zeta in patients with renal anaemia. Presented at European Dialysis and Transplant Nurses Association/European Renal Care Association conference (EDTNA/ERCA), Prague, Czech Republic 6-9 September 2008. Abstract P05.
3. Scigalla P, Koytchev R. Efficacy of epoetin zeta in renal anaemia: comparing patients aged >65 years and ≤ 65 years. Presented at European Dialysis and Transplant Nurses Association/European Renal Care Association conference (EDTNA/ERCA), Prague, Czech Republic 6-9 September 2008. Abstract P06.
4. Krivoshiev S, Todorov VV, Manitius J, Czekalski S, Scigalla P and Koytchev R on behalf of the Epoetin Zeta Study Group. Comparison of the therapeutic effects of epoetin zeta and epoetin alfa in the correction of renal anaemia. Curr Med Res Opin 2008; 24(5): 1407-1415.
5. Wizemann V, Rutkowski B, Baldamus C et al. Comparison of the therapeutic effects of epoetin zeta to epoetin alfa in the maintenance phase of renal anaemia treatment [published erratum in Curr Med Res Opin 2008; 24(4): 1155]. Curr Med Res Opin 2008; 24(3): 625-637.
6. European Medicines Agency (EMEA) European Public Assessment Report: Retacrit®. Available at emea.europa.eu. Accessed September 2008.
Hospira
Banked Blood Could Do More Harm Than Good
Two US studies suggest that almost as soon as it has been donated, banked human blood loses the vital ability to transfer oxygen to body
tissue that desperately needs it. The researchers say that for the majority of patients, blood transfusions with banked human blood could do more harm than good.
The studies are to be published in the early online issue of the Proceedings of the National Academy of Sciences (PNAS) and are the work of two teams
of scientists at Duke University Medical Center in Durham, North Carolina.
Almost immediately after it leaves the body, human blood begins to lose an essential gas, nitric oxide which is believed to be crucial to the delivery of
oxygen to tissues because it keeps the tiny blood vessels inside the tissue mass open. The researchers also believe that it helps red blood cells to stay
flexible so they can easily fit into the narrow constraints of the blood vessels.
The last five years has seen a number of studies, some of which were carried out at Duke's, showing that patients who received blood transfusions had higher
rates of heart attack, heart failure, stroke, and even death. But while scientists knew that banked blood was not the same as the blood in the body they did
not know why it should carry these risks.
Th Duke researchers have also carried out early experiments using dogs to show that adding nitric oxide to banked blood restores its ability to deliver
oxygen. It now needs to be proved in humans through clinical trials said the researchers.
Senior author of one of the papers, Dr Jonathan Stamler, George Barth Geller Professor for Research in Cardiovascular Diseases at Duke's said:
"It doesn't matter how much oxygen is being carried by red blood cells, it cannot get to the tissues that need it without nitric oxide."
Stamler's team originally discovered the importance of nitric oxide to the delivery of oxygen from red blood cells.
"Nitric oxide opens up the tiny blood vessels, allowing red blood cells to pass and deliver oxygen. If the blood vessels cannot open, the red blood cells
back up in the vessel and tissues go without oxygen. The result can be a heart attack or even death," said Stamler.
According to the new studies, nitric oxide in red blood cells starts to break down soon after red blood cells leave the body.
"The issue of transfused blood being potentially harmful to patients is one of the biggest problems facing American medicine," explained Stamler.
While blood transfusions are critically important, and banked blood can be a life saver, there are times when it can make things worse. Having this
knowledge about nitric oxide, which still needs to be proven in humans through clinical trials, means "in principle, we now have a solution to the nitric
oxide problem," he added.
Nearly 5 million Americans receive about 14 million units of red blood cells every year, the researchers said, according to estimates.
Donated blood has to be used within 42 days of donation. After that unused blood has to be discarded. "Banked blood is truly a national treasure that needs
to be protected," said Stamler.
The other study on the role of nitric oxide in banked blood that is to be published in PNAS was also carried out by Duke researchers, led by associate
professor of pulmonary medicine, Dr Timothy McMahon.
McMahon's group studied the changing properties of banked blood during the 42 days of storage. They tested human blood that was being kept according to the
national standards for the storage of banked blood by taking samples at regular intervals.
They were surprised at how quickly it changed, said McMahon:
"We saw clear indications of nitric oxide depletion within the first three hours."
"Of concern to us is that nitric oxide levels become depressed soon after collection, suggesting that even "fresh" blood may have adverse biological
characteristics," he added.
They discovered that as well as being essential for offloading oxygen to tissue, nitric oxide also plays a part in keeping red blood cells flexible. As the
levels of nitric oxide recede, so the saucer shaped cells get stiffer, so they don't bend and flex easily into the narrow blood vessels in the
tissue.
To test whether putting nitric oxide back into the stored blood would affect its ability to supply oxygen, Stamler and his team used dogs.
They showed that when they gave stored blood to the oxygen deprived animals, the blood flow did not increase properly. Yet paradoxically stored blood is
often given to heart patients to prevent heart attacks. This experiment showed that doing this could actually be increasing the risk of a heart attack.
When they added nitric oxide to the stored blood they gave to the dogs, blood flow to the heart was increased, indicating the blood vessels were sufficiently
dilated to allow passage of the blood cells and oxygen transfer to take place.
"This suggests that adding nitric oxide to human banked blood could theoretically improve its ability dilate blood vessels and thus prevent heart attacks and
even death in patients," said the researchers.
A large-scale randomized clinical trial in humans is needed, said McMahon and Stamler. These studies show that donated blood has risks as well as benefits,
and therefore should undergo clinical trials in the same way as drugs and medication.
There is no doubt that transfused blood can be harmful, they said. In any medical treatment, there are benefits and there are risks. In the case of banked
blood, the risks now need to be properly evaluated:
"We are only uncertain about how serious the problem is," said Stamler.
"The availability of a potential solution will hopefully focus the attention of the medical community on the potential magnitude of this problem," he
added.
"S-nitrosohemoglobin deficiency: A mechanism for loss of physiological activity in banked blood."
James D. Reynolds, Gregory S. Ahearn, Michael Angelo, Jian Zhang, Fred Cobb, and Jonathan S. Stamler.
Published 11 October 2007, 10.1073/pnas.0707958104
Click here for Abstract.
"Evolution of adverse changes in stored RBCs."
Elliott Bennett-Guerrero, Tim H. Veldman, Allan Doctor, Marilyn J. Telen, Thomas L. Ortel, T. Scott Reid, Melissa A. Mulherin, Hongmei Zhu, Raymond D. Buck, Robert M. Califf, and Timothy J. McMahon.
Published 11 October 2007, 10.1073/pnas.0708160104
Click here for Abstract.
Written by: Catharine Paddock
tissue that desperately needs it. The researchers say that for the majority of patients, blood transfusions with banked human blood could do more harm than good.
The studies are to be published in the early online issue of the Proceedings of the National Academy of Sciences (PNAS) and are the work of two teams
of scientists at Duke University Medical Center in Durham, North Carolina.
Almost immediately after it leaves the body, human blood begins to lose an essential gas, nitric oxide which is believed to be crucial to the delivery of
oxygen to tissues because it keeps the tiny blood vessels inside the tissue mass open. The researchers also believe that it helps red blood cells to stay
flexible so they can easily fit into the narrow constraints of the blood vessels.
The last five years has seen a number of studies, some of which were carried out at Duke's, showing that patients who received blood transfusions had higher
rates of heart attack, heart failure, stroke, and even death. But while scientists knew that banked blood was not the same as the blood in the body they did
not know why it should carry these risks.
Th Duke researchers have also carried out early experiments using dogs to show that adding nitric oxide to banked blood restores its ability to deliver
oxygen. It now needs to be proved in humans through clinical trials said the researchers.
Senior author of one of the papers, Dr Jonathan Stamler, George Barth Geller Professor for Research in Cardiovascular Diseases at Duke's said:
"It doesn't matter how much oxygen is being carried by red blood cells, it cannot get to the tissues that need it without nitric oxide."
Stamler's team originally discovered the importance of nitric oxide to the delivery of oxygen from red blood cells.
"Nitric oxide opens up the tiny blood vessels, allowing red blood cells to pass and deliver oxygen. If the blood vessels cannot open, the red blood cells
back up in the vessel and tissues go without oxygen. The result can be a heart attack or even death," said Stamler.
According to the new studies, nitric oxide in red blood cells starts to break down soon after red blood cells leave the body.
"The issue of transfused blood being potentially harmful to patients is one of the biggest problems facing American medicine," explained Stamler.
While blood transfusions are critically important, and banked blood can be a life saver, there are times when it can make things worse. Having this
knowledge about nitric oxide, which still needs to be proven in humans through clinical trials, means "in principle, we now have a solution to the nitric
oxide problem," he added.
Nearly 5 million Americans receive about 14 million units of red blood cells every year, the researchers said, according to estimates.
Donated blood has to be used within 42 days of donation. After that unused blood has to be discarded. "Banked blood is truly a national treasure that needs
to be protected," said Stamler.
The other study on the role of nitric oxide in banked blood that is to be published in PNAS was also carried out by Duke researchers, led by associate
professor of pulmonary medicine, Dr Timothy McMahon.
McMahon's group studied the changing properties of banked blood during the 42 days of storage. They tested human blood that was being kept according to the
national standards for the storage of banked blood by taking samples at regular intervals.
They were surprised at how quickly it changed, said McMahon:
"We saw clear indications of nitric oxide depletion within the first three hours."
"Of concern to us is that nitric oxide levels become depressed soon after collection, suggesting that even "fresh" blood may have adverse biological
characteristics," he added.
They discovered that as well as being essential for offloading oxygen to tissue, nitric oxide also plays a part in keeping red blood cells flexible. As the
levels of nitric oxide recede, so the saucer shaped cells get stiffer, so they don't bend and flex easily into the narrow blood vessels in the
tissue.
To test whether putting nitric oxide back into the stored blood would affect its ability to supply oxygen, Stamler and his team used dogs.
They showed that when they gave stored blood to the oxygen deprived animals, the blood flow did not increase properly. Yet paradoxically stored blood is
often given to heart patients to prevent heart attacks. This experiment showed that doing this could actually be increasing the risk of a heart attack.
When they added nitric oxide to the stored blood they gave to the dogs, blood flow to the heart was increased, indicating the blood vessels were sufficiently
dilated to allow passage of the blood cells and oxygen transfer to take place.
"This suggests that adding nitric oxide to human banked blood could theoretically improve its ability dilate blood vessels and thus prevent heart attacks and
even death in patients," said the researchers.
A large-scale randomized clinical trial in humans is needed, said McMahon and Stamler. These studies show that donated blood has risks as well as benefits,
and therefore should undergo clinical trials in the same way as drugs and medication.
There is no doubt that transfused blood can be harmful, they said. In any medical treatment, there are benefits and there are risks. In the case of banked
blood, the risks now need to be properly evaluated:
"We are only uncertain about how serious the problem is," said Stamler.
"The availability of a potential solution will hopefully focus the attention of the medical community on the potential magnitude of this problem," he
added.
"S-nitrosohemoglobin deficiency: A mechanism for loss of physiological activity in banked blood."
James D. Reynolds, Gregory S. Ahearn, Michael Angelo, Jian Zhang, Fred Cobb, and Jonathan S. Stamler.
Published 11 October 2007, 10.1073/pnas.0707958104
Click here for Abstract.
"Evolution of adverse changes in stored RBCs."
Elliott Bennett-Guerrero, Tim H. Veldman, Allan Doctor, Marilyn J. Telen, Thomas L. Ortel, T. Scott Reid, Melissa A. Mulherin, Hongmei Zhu, Raymond D. Buck, Robert M. Califf, and Timothy J. McMahon.
Published 11 October 2007, 10.1073/pnas.0708160104
Click here for Abstract.
Written by: Catharine Paddock
World Blood Donor Day: New Blood For The World
People under the age of 25 contribute an estimated 38% of reported voluntary blood donations, according to new global data from the WHO, released on World Blood Donor Day, 14 June.
World Blood Donor Day is celebrated each year to highlight the contribution voluntary unpaid blood donors make to public health. This year's slogan, "New blood for the world," aims to raise awareness of the role young people play in maintaining supplies of safe blood.
"This is the first time we have data for blood donation by age," said Carissa Etienne, Assistant Director-General for Health Systems and Services at WHO. "It's important to see that in many countries a lot of young people are already giving blood. Countries can use this to encourage more young people to become donors."
Figures from the 2008 Blood Safety Survey1 reveal that 14 countries collect more than half of their total donations from under 25s: Botswana, Burkina Faso, Gabon, Guinea, India, Jordan, Kiribati, Lao People's Democratic Republic, Malawi, Papua New Guinea, Republic of Korea, Tuvalu, Viet Nam, and Zimbabwe .
Standard age limits for blood donation are 18 to 65 years of age, but in some countries donations are accepted from people as young as 16 years, provided their parents consent. Voluntary unpaid donations are preferred over paid donations because supplies are generally safer, and there is less risk of donor exploitation. Evidence suggests that voluntary donations also promote other healthy lifestyle choices among young donors.
"Young people are the hope and future of a safe blood supply in the world," said Dr Neelam Dhingra, Coordinator of Blood Transfusion Safety at WHO. "We are confident more countries can achieve 100 per cent voluntary unpaid blood donation if they focus efforts on engaging young people."
Today, 62 countries obtain all, or nearly all (more than 99%), of their blood supplies from unpaid donors - up from 57 last year. Belarus, Islamic Republic of Iran, Kenya, Malaysia and Zambia are the latest to join this list.
"In 77 countries, however, donations are still well below the level required to meet patients' needs," Dr Dhingra added.
WHO recommends that blood donation by at least 1% a country's population is generally sufficient to meet a country's basic requirements for safe blood. Requirements are higher in countries with more developed health systems. Among the greatest needs: to replace blood lost in childbirth (a major cause of maternal deaths worldwide), and to treat the anaemia that threatens the lives of thousands of children who have malaria or are undernourished.
In May 2010, WHO Member States agreed on a resolution on the availability, safety and quality of blood products. The resolution paves the way to increase access to safe blood transfusions and to safe and affordable blood products in developing countries. It also echoes the Melbourne Declaration, released on World Blood Donor Day 2009 in Melbourne, Australia, which calls on countries to achieve 100% voluntary unpaid blood donation by 2020.
Starting 14 June, a week-long programme of high-profile events celebrate voluntary blood donation. This year, international World Blood Donor Day events are taking place in Barcelona, Spain and at Expo 2010 in Shanghai, China. A number of communities, including Barcelona, will gather volunteers in a prominent public space to stand together all dressed in red in the form of a "blood drop" as part of their celebration.
1 Age results were not reported by every country.
Source
WHO
World Blood Donor Day is celebrated each year to highlight the contribution voluntary unpaid blood donors make to public health. This year's slogan, "New blood for the world," aims to raise awareness of the role young people play in maintaining supplies of safe blood.
"This is the first time we have data for blood donation by age," said Carissa Etienne, Assistant Director-General for Health Systems and Services at WHO. "It's important to see that in many countries a lot of young people are already giving blood. Countries can use this to encourage more young people to become donors."
Figures from the 2008 Blood Safety Survey1 reveal that 14 countries collect more than half of their total donations from under 25s: Botswana, Burkina Faso, Gabon, Guinea, India, Jordan, Kiribati, Lao People's Democratic Republic, Malawi, Papua New Guinea, Republic of Korea, Tuvalu, Viet Nam, and Zimbabwe .
Standard age limits for blood donation are 18 to 65 years of age, but in some countries donations are accepted from people as young as 16 years, provided their parents consent. Voluntary unpaid donations are preferred over paid donations because supplies are generally safer, and there is less risk of donor exploitation. Evidence suggests that voluntary donations also promote other healthy lifestyle choices among young donors.
"Young people are the hope and future of a safe blood supply in the world," said Dr Neelam Dhingra, Coordinator of Blood Transfusion Safety at WHO. "We are confident more countries can achieve 100 per cent voluntary unpaid blood donation if they focus efforts on engaging young people."
Today, 62 countries obtain all, or nearly all (more than 99%), of their blood supplies from unpaid donors - up from 57 last year. Belarus, Islamic Republic of Iran, Kenya, Malaysia and Zambia are the latest to join this list.
"In 77 countries, however, donations are still well below the level required to meet patients' needs," Dr Dhingra added.
WHO recommends that blood donation by at least 1% a country's population is generally sufficient to meet a country's basic requirements for safe blood. Requirements are higher in countries with more developed health systems. Among the greatest needs: to replace blood lost in childbirth (a major cause of maternal deaths worldwide), and to treat the anaemia that threatens the lives of thousands of children who have malaria or are undernourished.
In May 2010, WHO Member States agreed on a resolution on the availability, safety and quality of blood products. The resolution paves the way to increase access to safe blood transfusions and to safe and affordable blood products in developing countries. It also echoes the Melbourne Declaration, released on World Blood Donor Day 2009 in Melbourne, Australia, which calls on countries to achieve 100% voluntary unpaid blood donation by 2020.
Starting 14 June, a week-long programme of high-profile events celebrate voluntary blood donation. This year, international World Blood Donor Day events are taking place in Barcelona, Spain and at Expo 2010 in Shanghai, China. A number of communities, including Barcelona, will gather volunteers in a prominent public space to stand together all dressed in red in the form of a "blood drop" as part of their celebration.
1 Age results were not reported by every country.
Source
WHO
Antisoma Initiates Phase IIb Trial Of AS1411 In Acute Myeloid Leukaemia
Antisoma plc (LSE: ASM; USOTC: ATSMY) announces that it has started a randomised, controlled, multi-territory, phase IIb trial of AS1411 in patients with acute myeloid leukaemia (AML).
Dr Ursula Ney, Chief Operating Officer of Antisoma, said: "AML is a devastating disease for which new treatment options are desperately needed. This phase IIb trial builds on earlier positive phase II findings, and is designed to pave the way for a registration trial of AS1411 in AML."
The phase IIb trial is enrolling patients with AML in first relapse or refractory to one prior treatment. Around 90 patients are being randomised to three treatment groups. A control group is receiving high-dose cytarabine, a standard chemotherapy treatment for this patient population. The other two groups are receiving high-dose cytarabine combined with AS1411 at 40 or 80 mg/kg/day.The trial will compare the three treatment groups with respect to safety, response rates, period free of leukaemia and survival. Data are expected next year.
The phase IIb trial follows a randomised phase II trial in AML, which reported positive results at the 2009 Annual Meeting of the American Society of Clinical Oncology (ASCO).
Except for the historical information presented, certain matters discussed in this statement are forward looking statements that are subject to a number of risks and uncertainties that could cause actual results to differ materially from results, performance or achievements expressed or implied by such statements. These risks and uncertainties may be associated with product discovery and development, including statements regarding the Group's clinical development programmes, the expected timing of clinical trials and regulatory filings. Such statements are based on management's current expectations, but actual results may differ materially.
About the AS1411 trials in AML
The phase IIb trial of AS1411 builds on data from an earlier phase II study reported at ASCO 2009. It evaluates a higher maximum dose of AS1411 (80 vs 40 mg/kg/day), uses a higher dose of cytarabine (4 vs 3 g/day) and is testing the drug in a refined patient population (patients in first relapse or refractory to one prior treatment vs all relapsed or refractory patients). The new trial is intended to identify the optimal dose of AS1411 for a pivotal AML trial and to provide a more detailed assessment of the benefit that could be achieved by adding AS1411 to standard chemotherapy in this setting. This is important in determining the number of patients to be included in a phase III registration trial and the design of such a study.
In the earlier phase II trial, patients were randomised to one of three treatment groups: high-dose cytarabine, high-dose cytarabine plus 10 mg/kg/day AS1411 or high-dose cytarabine plus 40 mg/kg/day AS1411. Response rates in the three treatment groups were 5% (1/19 patients), 21% (4/19 patients) and 19% (4/21 patients), respectively. Addition of AS1411 to high-dose cytarabine was well tolerated at both the 10 and 40 mg/kg/day doses, with most side-effects observed being those typically associated with cytarabine treatment.
About AS1411
AS1411 belongs to a new type of drug called aptamers. These drugs are short pieces of DNA or RNA that fold into three-dimensional structures capable of targeting particular proteins. AS1411 is a DNA aptamer that targets nucleolin, a protein found on the surface of cancer cells.
AS1411 was originally developed by Dr Paula Bates, Dr John Trent and Prof. Donald Miller at the University of Alabama and then at the University of Louisville. Antisoma added AS1411 to its pipeline when it acquired the Louisville-based company Aptamera Inc. in 2005.
AS1411 has been granted orphan drug status in both the United States and the European Union for the treatment of acute myeloid leukaemia (AML). The grants will provide seven years of market exclusivity in the US and ten years of exclusivity in the EU if AS1411 is approved for use in AML.
Source
Antisoma
Dr Ursula Ney, Chief Operating Officer of Antisoma, said: "AML is a devastating disease for which new treatment options are desperately needed. This phase IIb trial builds on earlier positive phase II findings, and is designed to pave the way for a registration trial of AS1411 in AML."
The phase IIb trial is enrolling patients with AML in first relapse or refractory to one prior treatment. Around 90 patients are being randomised to three treatment groups. A control group is receiving high-dose cytarabine, a standard chemotherapy treatment for this patient population. The other two groups are receiving high-dose cytarabine combined with AS1411 at 40 or 80 mg/kg/day.The trial will compare the three treatment groups with respect to safety, response rates, period free of leukaemia and survival. Data are expected next year.
The phase IIb trial follows a randomised phase II trial in AML, which reported positive results at the 2009 Annual Meeting of the American Society of Clinical Oncology (ASCO).
Except for the historical information presented, certain matters discussed in this statement are forward looking statements that are subject to a number of risks and uncertainties that could cause actual results to differ materially from results, performance or achievements expressed or implied by such statements. These risks and uncertainties may be associated with product discovery and development, including statements regarding the Group's clinical development programmes, the expected timing of clinical trials and regulatory filings. Such statements are based on management's current expectations, but actual results may differ materially.
About the AS1411 trials in AML
The phase IIb trial of AS1411 builds on data from an earlier phase II study reported at ASCO 2009. It evaluates a higher maximum dose of AS1411 (80 vs 40 mg/kg/day), uses a higher dose of cytarabine (4 vs 3 g/day) and is testing the drug in a refined patient population (patients in first relapse or refractory to one prior treatment vs all relapsed or refractory patients). The new trial is intended to identify the optimal dose of AS1411 for a pivotal AML trial and to provide a more detailed assessment of the benefit that could be achieved by adding AS1411 to standard chemotherapy in this setting. This is important in determining the number of patients to be included in a phase III registration trial and the design of such a study.
In the earlier phase II trial, patients were randomised to one of three treatment groups: high-dose cytarabine, high-dose cytarabine plus 10 mg/kg/day AS1411 or high-dose cytarabine plus 40 mg/kg/day AS1411. Response rates in the three treatment groups were 5% (1/19 patients), 21% (4/19 patients) and 19% (4/21 patients), respectively. Addition of AS1411 to high-dose cytarabine was well tolerated at both the 10 and 40 mg/kg/day doses, with most side-effects observed being those typically associated with cytarabine treatment.
About AS1411
AS1411 belongs to a new type of drug called aptamers. These drugs are short pieces of DNA or RNA that fold into three-dimensional structures capable of targeting particular proteins. AS1411 is a DNA aptamer that targets nucleolin, a protein found on the surface of cancer cells.
AS1411 was originally developed by Dr Paula Bates, Dr John Trent and Prof. Donald Miller at the University of Alabama and then at the University of Louisville. Antisoma added AS1411 to its pipeline when it acquired the Louisville-based company Aptamera Inc. in 2005.
AS1411 has been granted orphan drug status in both the United States and the European Union for the treatment of acute myeloid leukaemia (AML). The grants will provide seven years of market exclusivity in the US and ten years of exclusivity in the EU if AS1411 is approved for use in AML.
Source
Antisoma
'Blood Cancer Awareness Month' Recognized By U.S. House Of Representatives
The U.S. House of Representatives passed House Resolution 1433, declaring September 2010 as 'Blood Cancer Awareness Month.' The resolution helps raise awareness and support for issues affecting blood cancer patients within the halls of the Capitol.
"Awareness Month is an opportunity to increase the public's understanding of blood cancers and encourage people to support the funding of research to find cures and education programs to help patients have the best possible outcomes throughout their cancer experience," explained John Walter, president and CEO of The Leukemia & Lymphoma Society. "The Leukemia & Lymphoma Society would like to thank Representatives Walter Jones and Betsey Markey for introducing and supporting this resolution, and all of our volunteers who called and emailed their representatives to urge their support."
Remarkable progress has been made in treating patients with blood cancers. Sixty years ago there were few effective treatments for children or adults with blood cancer and the rate of survival was very low. Today, about 75 percent of children with acute leukemia and nearly 80 percent of children and adults with Hodgkin lymphoma are cured. Advances in the treatment of blood cancers have also led to new treatments for other cancers. In fact, in the last decade, 47 percent of new cancer therapies approved by the Food and Drug Administration (FDA) were first developed and approved to treat a blood cancer.
Despite these advances, more than 900,000 people in the United States currently have some form of blood cancer and fewer than 50 percent of newly diagnosed patients will survive five years past that diagnosis. Every ten minutes someone dies from a blood cancer and more than 53,000 will die from one this year.
"Congress has been supportive of issues affecting blood cancers in the past," said Walter, "and we thank them for that support. But more needs to be done to fight these deadly diseases increased research funding, access to affordable treatments, and improved care planning for survivors, just to name a few issues that need to be addressed."
Source: Leukemia & Lymphoma Society
"Awareness Month is an opportunity to increase the public's understanding of blood cancers and encourage people to support the funding of research to find cures and education programs to help patients have the best possible outcomes throughout their cancer experience," explained John Walter, president and CEO of The Leukemia & Lymphoma Society. "The Leukemia & Lymphoma Society would like to thank Representatives Walter Jones and Betsey Markey for introducing and supporting this resolution, and all of our volunteers who called and emailed their representatives to urge their support."
Remarkable progress has been made in treating patients with blood cancers. Sixty years ago there were few effective treatments for children or adults with blood cancer and the rate of survival was very low. Today, about 75 percent of children with acute leukemia and nearly 80 percent of children and adults with Hodgkin lymphoma are cured. Advances in the treatment of blood cancers have also led to new treatments for other cancers. In fact, in the last decade, 47 percent of new cancer therapies approved by the Food and Drug Administration (FDA) were first developed and approved to treat a blood cancer.
Despite these advances, more than 900,000 people in the United States currently have some form of blood cancer and fewer than 50 percent of newly diagnosed patients will survive five years past that diagnosis. Every ten minutes someone dies from a blood cancer and more than 53,000 will die from one this year.
"Congress has been supportive of issues affecting blood cancers in the past," said Walter, "and we thank them for that support. But more needs to be done to fight these deadly diseases increased research funding, access to affordable treatments, and improved care planning for survivors, just to name a few issues that need to be addressed."
Source: Leukemia & Lymphoma Society
PROCRIT® (Epoetin Alfa) Data To Be Presented At American Society Of Hematology Annual Meeting
Data from 11 PROCRIT® (Epoetin alfa) studies will be presented at the American Society of Hematology (ASH) 49th Annual Meeting and Exposition December 8 - 11, 2007.
The data will provide important insights including:
-- the potential impact on the nation's blood supply of limiting the use of erythropoiesis-stimulating agents (ESAs) for the treatment of chemotherapy-induced anemia (CIA);
-- the use of PROCRIT® in extended dosing regimens;
-- the use of PROCRIT® for treatment of transfusion-dependent anemia in patients with myelodysplastic syndromes (MDS);
-- PROCRIT® and real-world practice patterns;
-- PROCRIT® in managed care settings; and
-- observational data from the Dosing Outcomes Study of Erythropoiesis-Stimulating Therapies (DOSE) Registry.
In some cases, the data are from investigational studies and do not reflect current U.S. Food and Drug Administration (FDA)-approved PROCRIT® indications or recommended dosage and administration. Please note that all information presented at ASH is embargoed for media release until the data are made available to the public on the ASH web site.
Data on the Potential Impact on Blood Supply of Limiting ESA Use for Chemotherapy Patients
Poster: Impact of Limiting Erythropoiesis-Stimulating Agent Use for Chemotherapy-Induced Anemia on the United States Blood Supply
Francis Vekeman, M.A., Groupe d'analyse, Ltee, Montreal, Quebec, Canada
Presentation: Monday, December 10, 2007; 5:00pm - 7:00pm; Hall B3 and B4 in the Georgia World Congress Center (Poster Board Number 115, Publication Number 2896)
A modeling simulation was employed to estimate the impact of limiting the use of ESAs for CIA on the U.S. blood supply. The model used a top-down approach to compare the number of red blood cell units transfused in ESA-treated patients to the number of red blood cell units that would be transfused if ESAs were discontinued or limited in the same population.
Data on PROCRIT® Investigational Extended Dosing Regimens
Abstract: Early vs. Standard Intervention With an Extended Epoetin alfa (EPO) Dose Regimen of 120,000 Units (U) Every 3 Weeks (Q3W) in Chemotherapy (CT)-Induced Anemia: Results for Elderly vs. Younger Patients in a Randomized Clinical Trial
Veena Charu, M.D., Pacific Cancer Medical Center, Inc., Anaheim, CA
Publication Number 3769
A retrospective subset analysis of a prospective, randomized, open-label, multi-center study compared key efficacy and safety results of elderly (n=62) and younger (n=73) patients with non-myeloid malignancy. Patients with chemotherapy planned for greater than or equal to nine weeks and baseline hemoglobin greater than or equal to 11 and less than or equal to 12 grams per deciliter (g/dL) were randomized either to "early" intervention with Epoetin alfa or to "standard" intervention with Epoetin alfa when hemoglobin decreased to
Abstract: Erythroid Response to Epoetin alfa (EPO) 120,000 Units (U) Every Three Weeks (Q3W) Initiated Early or at a Standard Threshold in Chemotherapy-Induced Anemia (CIA)
Veena Charu, M.D., Pacific Cancer Medical Center, Inc., Anaheim, CA
Publication Number 3770
A retrospective analysis of observed hematologic profiles from a 16-week, open-label, randomized study enrolled patients with non-myeloid malignancy, baseline hemoglobin greater than or equal to 11 and less than or equal to 12 g/dL, and chemotherapy planned for greater than or equal to nine weeks to evaluate whether hemoglobin levels could be adequately maintained with Q3W Epoetin alfa initiation treatment. Patients were randomized according to study protocol to "early" or "standard" intervention groups (n=68 in each group).
Abstract: Investigation of Epoetin alfa (EPO) 80,000 Units (U) Every four Weeks (Q4W) vs. 40,000 U Every 2 Weeks (Q2W) in Patients with Cancer Not Receiving Chemotherapy (CT) or Radiation Therapy (RT): Final Results
Daniel Shasha, M.D., Beth Israel Medical Center, New York, NY
Publication Number 3775
This prospective, randomized, open-label, multi-center pilot study with 100 patients with an active non-myeloid malignancy, baseline hemoglobin level less than or equal to 11 g/dL, and not receiving or planning to receive CT or RT during the course of the study, was designed to investigate two novel dosing regimens in this population. Based on recent safety concerns from studies with another ESA in cancer patients not receiving CT or RT, enrollment in this study was stopped prior to the planned enrollment.
Data on PROCRIT® for the Investigational Treatment of Transfusion-Dependent Anemia in MDS Patients
Poster: Treatment of MDS Related Transfusion-Dependent Anemia With Epoetin alfa: A Meta-Analysis Perspective
Suneel Mundle, Ph.D., Ortho Biotech Clinical Affairs, LLC, Bridgewater, NJ
Presentation: Saturday, December 8, 2007; 5:30pm - 7:30pm; Hall B3 and B4 in the Georgia World Congress Center (Poster Board Number 625, Publication Number 1471) A meta-analysis of data extracted from studies found in PubMed, American Society of Clinical Oncology (ASCO) and ASH proceedings from 1990 to 2006 in transfusion-dependent MDS patients (n=578) treated with Epoetin alfa plus or minus granulocyte and granulocyte-macrophage colony stimulating factors (G/GM-CSF) assessed the efficacy of Epoetin alfa in achieving transfusion independence in transfusion-dependent MDS patients.
Abstract: Drug Utilization and Cost Considerations of Erythropoiesis-Stimulating Agents in Patients with Myelodysplastic Syndromes
Francois Laliberte, M.A., Groupe d'analyse, Ltee, Montreal, Quebec, Canada
Publication Number 4611
A retrospective analysis of medical claims examined Epoetin alfa and darbepoetin alfa dosing patterns, ESA treatment costs and red blood cell transfusion use in order to characterize real-world utilization of ESAs in adult patients with MDS.
Abstract: Assessment of Epoetin alfa in Patients with Myelodysplastic Syndrome Utilizing an Electronic Medical Record Database
Bruce Feinberg, D.O., Georgia Cancer Center Oncology, Decatur, GA
Publication Number 5180
A retrospective, observational study, using electronic medical record data from a large oncology/hematology practice in the southeastern United States, was conducted to gain a better understanding of the demographics, real-world treatment patterns and clinical outcomes for patients with MDS receiving Epoetin alfa.
Data on PROCRIT® and Real-World Practice Patterns
Poster: Erythropoiesis-Stimulating Agents for Chemotherapy Induced Anemia: Analysis of an Electronic Medical Record Database within a Large Oncology/Hematology Practice
Bruce Feinberg, D.O., Georgia Cancer Center Oncology, Decatur, GA
Presentation: Saturday, December 8, 2007; 5:30pm - 7:30pm, Hall B3 and B4 in the Georgia World Congress Center (Poster Board Number 117, Publication Number 963) A retrospective, observational study using electronic medical record data from a large oncology/hematology practice in the southeastern United States was conducted to gain a better understanding of real- world treatment patterns and clinical outcomes in patients with cancer receiving chemotherapy and ESA therapy.
Data on PROCRIT® in Managed Care Settings
Abstract: Drug Utilization Patterns and Cost Considerations for Erythropoiesis Stimulating Agents in Cancer Chemotherapy Patients in a Managed Care Setting
Alyson Mandel, Ph.D., Medical Practice Data Corporation, Claverack, NY
Publication Number 5157
A retrospective, observational analysis of ESA utilization in more than 4,100 chemotherapy patients using adjudicated medical claims between 2004 and 2006 from seven health plans was conducted to understand current utilization patterns. The study examined real-world dosing and drug costs for ESAs (Epoetin alfa and darbepoetin alfa) in cancer patients receiving chemotherapy.
Abstract: Medical Visit Patterns in Cancer Chemotherapy Patients Receiving Erythropoiesis Stimulating Agents in a Managed Care Setting Alyson Mandel, Ph.D., Medical Practice Data Corporation, Claverack, NY
Publication Number 5156
A retrospective analysis of medical claims between January 2004 and December 2005 using the Integrated Health Care Information Systems national database and representing more than 35 health plans was conducted to describe visit patterns and identify the proportion of medical visits made exclusively for ESA treatment in cancer chemotherapy patients.
Observational Data from the DOSE Registry
Abstract: Hemoglobin Levels Prior To Blood Transfusions In Oncology Patients Receiving Chemotherapy and Erythropoiesis-Stimulating Agents (ESAs): Observational Data from the DOSE Registry
Kay Larholt, Sc.D., Abt Associates, Lexington, MA
Publication Number 4019
A retrospective analysis of real-world data from ESA-treated oncology patients obtained from an ongoing prospective, observational registry, Dosing and Outcomes Study of Erythropoiesis-Stimulating Therapies (DOSE), to characterize hemoglobin levels or transfusion triggers. Data were collected from participating hospital- and community-based outpatient practices between December 2003 and July 2007.
About PROCRIT® (Epoetin alfa)
PROCRIT® is used for the treatment of anemia in patients with most types of cancer receiving chemotherapy, with chronic renal failure who are on dialysis and those who are not on dialysis, who are being treated with zidovudine for HIV infection, and to reduce the need for transfusion in anemic patients who are scheduled for elective noncardiac, nonvascular surgery. Depending on the country in which Epoetin alfa is marketed, these indications may differ.
Important U.S. Safety Information for PROCRIT®
Boxed WARNINGS: INCREASED MORTALITY, SERIOUS CARDIOVASCULAR AND THROMBOEMBOLIC EVENTS, and TUMOR PROGRESSION
Renal failure: Patients experienced greater risks for death and serious cardiovascular events when administered erythropoiesis-stimulating agents (ESAs) to target higher versus lower hemoglobin levels (13.5 vs. 11.3 g/dL; 14 vs. 10 g/dL) in two clinical studies. Individualize dosing to achieve and maintain hemoglobin levels within the range of 10 to 12 g/dL.
Cancer:
-- ESAs shortened overall survival and/or time-to-tumor progression in clinical studies in patients with advanced breast, head and neck, lymphoid, and non-small cell lung malignancies when dosed to target a hemoglobin of greater than or equal to 12 g/dL.
-- The risks of shortened survival and tumor progression have not been excluded when ESAs are dosed to target a hemoglobin of < 12 g/dL.
-- To minimize these risks, as well as the risk of serious cardio- and thrombovascular events, use the lowest dose needed to avoid red blood cell transfusions.
-- Use only for treatment of anemia due to concomitant myelosuppressive chemotherapy.
-- Discontinue following the completion of a chemotherapy course.
Perisurgery: PROCRIT® increased the rate of deep venous thromboses in patients not receiving prophylactic anticoagulation. Consider deep venous thrombosis prophylaxis.
Contraindications
PROCRIT® is contraindicated in patients with uncontrolled hypertension or with known hypersensitivity to albumin (human) or mammalian cell-derived products.
Additional Important Safety Information
-- The dose of PROCRIT® should be titrated for each patient to achieve and maintain the following hemoglobin levels:
-- Chronic renal failure patients -- hemoglobin levels between 10 to 12 g/dL. If a patient does not attain hemoglobin levels of 10 to 12 g/dL despite 12 weeks of appropriate PROCRIT® therapy, see DOSAGE and ADMINISTRATION in the PROCRIT® Prescribing Information.
-- Cancer or HIV patients -- the lowest hemoglobin level sufficient to avoid transfusion and not to exceed 12 g/dL.
-- Monitor hemoglobin regularly during therapy, more frequently following a dosage adjustment or until hemoglobin becomes stable.
-- Cases of pure red cell aplasia (PRCA) and of severe anemia, with or without other cytopenias, associated with neutralizing antibodies to erythropoietin have been reported in patients with chronic renal failure receiving PROCRIT® by subcutaneous administration. If any patient develops a sudden loss of response to PROCRIT®, accompanied by severe anemia and low reticulocyte count, and anti-erythropoietin antibody-associated anemia is suspected, withhold PROCRIT® and other erythropoietic proteins. If erythropoietin antibody-mediated anemia is confirmed, PROCRIT® should be permanently discontinued and patients should not be switched to other erythropoietic proteins.
-- The safety and efficacy of PROCRIT® therapy have not been established in patients with a known history of a seizure disorder or underlying hematologic disease (e.g., sickle cell anemia, myelodysplastic syndromes or hypercoagulable disorders).
-- In some female patients, menses have resumed following PROCRIT® therapy; the possibility of pregnancy should be discussed and the need for contraception evaluated.
-- Prior to and regularly during PROCRIT® therapy monitor iron status; transferrin saturation should be greater than or equal to 20 percent and ferritin should be greater than or equal to 100 ng/mL. During therapy absolute or functional iron deficiency may develop and all patients will eventually require supplemental iron to adequately support erythropoiesis stimulated by PROCRIT®.
-- During PROCRIT® therapy, blood pressure should be monitored carefully and aggressively managed, particularly in patients with an underlying history of hypertension or cardiovascular disease.
-- In studies, the most common side effects included fever (pyrexia), diarrhea, nausea, vomiting, swelling of hands or feet (edema), lack or loss of strength or weakness (asthenia, fatigue), shortness of breath, high blood pressure, headache, joint pain (arthralgias), abnormal skin sensations (as tingling or tickling or itching or burning; paresthesia), rash, constipation and upper respiratory infection.
Please visit procrit for the full Prescribing Information, including the Boxed WARNINGS.
About Ortho Biotech Products, L.P.
Ortho Biotech Products, L.P. is a leading biopharmaceutical company devoted to helping improve the lives of patients with cancer and with anemia due to multiple causes, including chronic kidney disease. Since it was founded in 1990, Ortho Biotech and its worldwide affiliates have earned a global reputation for researching, manufacturing and marketing innovative products that enhance patients' health. Located in Bridgewater, N.J., Ortho Biotech is an established market leader in Epoetin alfa therapy for anemia management. The company also markets treatments for recurrent ovarian cancer, rejection of transplanted organs and other serious illnesses. For more information, visit orthobiotech.
The data will provide important insights including:
-- the potential impact on the nation's blood supply of limiting the use of erythropoiesis-stimulating agents (ESAs) for the treatment of chemotherapy-induced anemia (CIA);
-- the use of PROCRIT® in extended dosing regimens;
-- the use of PROCRIT® for treatment of transfusion-dependent anemia in patients with myelodysplastic syndromes (MDS);
-- PROCRIT® and real-world practice patterns;
-- PROCRIT® in managed care settings; and
-- observational data from the Dosing Outcomes Study of Erythropoiesis-Stimulating Therapies (DOSE) Registry.
In some cases, the data are from investigational studies and do not reflect current U.S. Food and Drug Administration (FDA)-approved PROCRIT® indications or recommended dosage and administration. Please note that all information presented at ASH is embargoed for media release until the data are made available to the public on the ASH web site.
Data on the Potential Impact on Blood Supply of Limiting ESA Use for Chemotherapy Patients
Poster: Impact of Limiting Erythropoiesis-Stimulating Agent Use for Chemotherapy-Induced Anemia on the United States Blood Supply
Francis Vekeman, M.A., Groupe d'analyse, Ltee, Montreal, Quebec, Canada
Presentation: Monday, December 10, 2007; 5:00pm - 7:00pm; Hall B3 and B4 in the Georgia World Congress Center (Poster Board Number 115, Publication Number 2896)
A modeling simulation was employed to estimate the impact of limiting the use of ESAs for CIA on the U.S. blood supply. The model used a top-down approach to compare the number of red blood cell units transfused in ESA-treated patients to the number of red blood cell units that would be transfused if ESAs were discontinued or limited in the same population.
Data on PROCRIT® Investigational Extended Dosing Regimens
Abstract: Early vs. Standard Intervention With an Extended Epoetin alfa (EPO) Dose Regimen of 120,000 Units (U) Every 3 Weeks (Q3W) in Chemotherapy (CT)-Induced Anemia: Results for Elderly vs. Younger Patients in a Randomized Clinical Trial
Veena Charu, M.D., Pacific Cancer Medical Center, Inc., Anaheim, CA
Publication Number 3769
A retrospective subset analysis of a prospective, randomized, open-label, multi-center study compared key efficacy and safety results of elderly (n=62) and younger (n=73) patients with non-myeloid malignancy. Patients with chemotherapy planned for greater than or equal to nine weeks and baseline hemoglobin greater than or equal to 11 and less than or equal to 12 grams per deciliter (g/dL) were randomized either to "early" intervention with Epoetin alfa or to "standard" intervention with Epoetin alfa when hemoglobin decreased to
Abstract: Erythroid Response to Epoetin alfa (EPO) 120,000 Units (U) Every Three Weeks (Q3W) Initiated Early or at a Standard Threshold in Chemotherapy-Induced Anemia (CIA)
Veena Charu, M.D., Pacific Cancer Medical Center, Inc., Anaheim, CA
Publication Number 3770
A retrospective analysis of observed hematologic profiles from a 16-week, open-label, randomized study enrolled patients with non-myeloid malignancy, baseline hemoglobin greater than or equal to 11 and less than or equal to 12 g/dL, and chemotherapy planned for greater than or equal to nine weeks to evaluate whether hemoglobin levels could be adequately maintained with Q3W Epoetin alfa initiation treatment. Patients were randomized according to study protocol to "early" or "standard" intervention groups (n=68 in each group).
Abstract: Investigation of Epoetin alfa (EPO) 80,000 Units (U) Every four Weeks (Q4W) vs. 40,000 U Every 2 Weeks (Q2W) in Patients with Cancer Not Receiving Chemotherapy (CT) or Radiation Therapy (RT): Final Results
Daniel Shasha, M.D., Beth Israel Medical Center, New York, NY
Publication Number 3775
This prospective, randomized, open-label, multi-center pilot study with 100 patients with an active non-myeloid malignancy, baseline hemoglobin level less than or equal to 11 g/dL, and not receiving or planning to receive CT or RT during the course of the study, was designed to investigate two novel dosing regimens in this population. Based on recent safety concerns from studies with another ESA in cancer patients not receiving CT or RT, enrollment in this study was stopped prior to the planned enrollment.
Data on PROCRIT® for the Investigational Treatment of Transfusion-Dependent Anemia in MDS Patients
Poster: Treatment of MDS Related Transfusion-Dependent Anemia With Epoetin alfa: A Meta-Analysis Perspective
Suneel Mundle, Ph.D., Ortho Biotech Clinical Affairs, LLC, Bridgewater, NJ
Presentation: Saturday, December 8, 2007; 5:30pm - 7:30pm; Hall B3 and B4 in the Georgia World Congress Center (Poster Board Number 625, Publication Number 1471) A meta-analysis of data extracted from studies found in PubMed, American Society of Clinical Oncology (ASCO) and ASH proceedings from 1990 to 2006 in transfusion-dependent MDS patients (n=578) treated with Epoetin alfa plus or minus granulocyte and granulocyte-macrophage colony stimulating factors (G/GM-CSF) assessed the efficacy of Epoetin alfa in achieving transfusion independence in transfusion-dependent MDS patients.
Abstract: Drug Utilization and Cost Considerations of Erythropoiesis-Stimulating Agents in Patients with Myelodysplastic Syndromes
Francois Laliberte, M.A., Groupe d'analyse, Ltee, Montreal, Quebec, Canada
Publication Number 4611
A retrospective analysis of medical claims examined Epoetin alfa and darbepoetin alfa dosing patterns, ESA treatment costs and red blood cell transfusion use in order to characterize real-world utilization of ESAs in adult patients with MDS.
Abstract: Assessment of Epoetin alfa in Patients with Myelodysplastic Syndrome Utilizing an Electronic Medical Record Database
Bruce Feinberg, D.O., Georgia Cancer Center Oncology, Decatur, GA
Publication Number 5180
A retrospective, observational study, using electronic medical record data from a large oncology/hematology practice in the southeastern United States, was conducted to gain a better understanding of the demographics, real-world treatment patterns and clinical outcomes for patients with MDS receiving Epoetin alfa.
Data on PROCRIT® and Real-World Practice Patterns
Poster: Erythropoiesis-Stimulating Agents for Chemotherapy Induced Anemia: Analysis of an Electronic Medical Record Database within a Large Oncology/Hematology Practice
Bruce Feinberg, D.O., Georgia Cancer Center Oncology, Decatur, GA
Presentation: Saturday, December 8, 2007; 5:30pm - 7:30pm, Hall B3 and B4 in the Georgia World Congress Center (Poster Board Number 117, Publication Number 963) A retrospective, observational study using electronic medical record data from a large oncology/hematology practice in the southeastern United States was conducted to gain a better understanding of real- world treatment patterns and clinical outcomes in patients with cancer receiving chemotherapy and ESA therapy.
Data on PROCRIT® in Managed Care Settings
Abstract: Drug Utilization Patterns and Cost Considerations for Erythropoiesis Stimulating Agents in Cancer Chemotherapy Patients in a Managed Care Setting
Alyson Mandel, Ph.D., Medical Practice Data Corporation, Claverack, NY
Publication Number 5157
A retrospective, observational analysis of ESA utilization in more than 4,100 chemotherapy patients using adjudicated medical claims between 2004 and 2006 from seven health plans was conducted to understand current utilization patterns. The study examined real-world dosing and drug costs for ESAs (Epoetin alfa and darbepoetin alfa) in cancer patients receiving chemotherapy.
Abstract: Medical Visit Patterns in Cancer Chemotherapy Patients Receiving Erythropoiesis Stimulating Agents in a Managed Care Setting Alyson Mandel, Ph.D., Medical Practice Data Corporation, Claverack, NY
Publication Number 5156
A retrospective analysis of medical claims between January 2004 and December 2005 using the Integrated Health Care Information Systems national database and representing more than 35 health plans was conducted to describe visit patterns and identify the proportion of medical visits made exclusively for ESA treatment in cancer chemotherapy patients.
Observational Data from the DOSE Registry
Abstract: Hemoglobin Levels Prior To Blood Transfusions In Oncology Patients Receiving Chemotherapy and Erythropoiesis-Stimulating Agents (ESAs): Observational Data from the DOSE Registry
Kay Larholt, Sc.D., Abt Associates, Lexington, MA
Publication Number 4019
A retrospective analysis of real-world data from ESA-treated oncology patients obtained from an ongoing prospective, observational registry, Dosing and Outcomes Study of Erythropoiesis-Stimulating Therapies (DOSE), to characterize hemoglobin levels or transfusion triggers. Data were collected from participating hospital- and community-based outpatient practices between December 2003 and July 2007.
About PROCRIT® (Epoetin alfa)
PROCRIT® is used for the treatment of anemia in patients with most types of cancer receiving chemotherapy, with chronic renal failure who are on dialysis and those who are not on dialysis, who are being treated with zidovudine for HIV infection, and to reduce the need for transfusion in anemic patients who are scheduled for elective noncardiac, nonvascular surgery. Depending on the country in which Epoetin alfa is marketed, these indications may differ.
Important U.S. Safety Information for PROCRIT®
Boxed WARNINGS: INCREASED MORTALITY, SERIOUS CARDIOVASCULAR AND THROMBOEMBOLIC EVENTS, and TUMOR PROGRESSION
Renal failure: Patients experienced greater risks for death and serious cardiovascular events when administered erythropoiesis-stimulating agents (ESAs) to target higher versus lower hemoglobin levels (13.5 vs. 11.3 g/dL; 14 vs. 10 g/dL) in two clinical studies. Individualize dosing to achieve and maintain hemoglobin levels within the range of 10 to 12 g/dL.
Cancer:
-- ESAs shortened overall survival and/or time-to-tumor progression in clinical studies in patients with advanced breast, head and neck, lymphoid, and non-small cell lung malignancies when dosed to target a hemoglobin of greater than or equal to 12 g/dL.
-- The risks of shortened survival and tumor progression have not been excluded when ESAs are dosed to target a hemoglobin of < 12 g/dL.
-- To minimize these risks, as well as the risk of serious cardio- and thrombovascular events, use the lowest dose needed to avoid red blood cell transfusions.
-- Use only for treatment of anemia due to concomitant myelosuppressive chemotherapy.
-- Discontinue following the completion of a chemotherapy course.
Perisurgery: PROCRIT® increased the rate of deep venous thromboses in patients not receiving prophylactic anticoagulation. Consider deep venous thrombosis prophylaxis.
Contraindications
PROCRIT® is contraindicated in patients with uncontrolled hypertension or with known hypersensitivity to albumin (human) or mammalian cell-derived products.
Additional Important Safety Information
-- The dose of PROCRIT® should be titrated for each patient to achieve and maintain the following hemoglobin levels:
-- Chronic renal failure patients -- hemoglobin levels between 10 to 12 g/dL. If a patient does not attain hemoglobin levels of 10 to 12 g/dL despite 12 weeks of appropriate PROCRIT® therapy, see DOSAGE and ADMINISTRATION in the PROCRIT® Prescribing Information.
-- Cancer or HIV patients -- the lowest hemoglobin level sufficient to avoid transfusion and not to exceed 12 g/dL.
-- Monitor hemoglobin regularly during therapy, more frequently following a dosage adjustment or until hemoglobin becomes stable.
-- Cases of pure red cell aplasia (PRCA) and of severe anemia, with or without other cytopenias, associated with neutralizing antibodies to erythropoietin have been reported in patients with chronic renal failure receiving PROCRIT® by subcutaneous administration. If any patient develops a sudden loss of response to PROCRIT®, accompanied by severe anemia and low reticulocyte count, and anti-erythropoietin antibody-associated anemia is suspected, withhold PROCRIT® and other erythropoietic proteins. If erythropoietin antibody-mediated anemia is confirmed, PROCRIT® should be permanently discontinued and patients should not be switched to other erythropoietic proteins.
-- The safety and efficacy of PROCRIT® therapy have not been established in patients with a known history of a seizure disorder or underlying hematologic disease (e.g., sickle cell anemia, myelodysplastic syndromes or hypercoagulable disorders).
-- In some female patients, menses have resumed following PROCRIT® therapy; the possibility of pregnancy should be discussed and the need for contraception evaluated.
-- Prior to and regularly during PROCRIT® therapy monitor iron status; transferrin saturation should be greater than or equal to 20 percent and ferritin should be greater than or equal to 100 ng/mL. During therapy absolute or functional iron deficiency may develop and all patients will eventually require supplemental iron to adequately support erythropoiesis stimulated by PROCRIT®.
-- During PROCRIT® therapy, blood pressure should be monitored carefully and aggressively managed, particularly in patients with an underlying history of hypertension or cardiovascular disease.
-- In studies, the most common side effects included fever (pyrexia), diarrhea, nausea, vomiting, swelling of hands or feet (edema), lack or loss of strength or weakness (asthenia, fatigue), shortness of breath, high blood pressure, headache, joint pain (arthralgias), abnormal skin sensations (as tingling or tickling or itching or burning; paresthesia), rash, constipation and upper respiratory infection.
Please visit procrit for the full Prescribing Information, including the Boxed WARNINGS.
About Ortho Biotech Products, L.P.
Ortho Biotech Products, L.P. is a leading biopharmaceutical company devoted to helping improve the lives of patients with cancer and with anemia due to multiple causes, including chronic kidney disease. Since it was founded in 1990, Ortho Biotech and its worldwide affiliates have earned a global reputation for researching, manufacturing and marketing innovative products that enhance patients' health. Located in Bridgewater, N.J., Ortho Biotech is an established market leader in Epoetin alfa therapy for anemia management. The company also markets treatments for recurrent ovarian cancer, rejection of transplanted organs and other serious illnesses. For more information, visit orthobiotech.
What Is a Nosebleed? What Causes Nosebleeds?
The medical term for nosebleed is epistaxis. We can also say nasal hemorrhage. The human nose, and those of many animals are rich in blood vessels. Because of the position of the nose - right in the middle of the face - and all its blood vessels, most of us will have had at least one nosebleed at some time during our lives.
According to Medilexicon's medical dictionary, epistaxis means "Bleeding from the nose". Nosebleeds are seldom a cause for alarm but can be life threatening in rare cases.
Spontaneous nosebleeds are fairly common, especially in children. When the mucous membrane (a mucus-secreting tissue) inside the nose dries, crusts, or cracks (the skin splits open) and is then picked, it is likely to bleed.
Because the nose is full of blood vessels and is inconveniently situated in the middle of the face, any minor injury to the face can cause the nose to bleed profusely.
Nosebleeds are also common in people taking anti-coagulants (blood-thinning medications, such as Aspirin), as well as in older people whose blood may take longer to clot. If the patient is taking anti-coagulants, has hypertension (high blood pressure), or a blood-clotting disorder, the bleeding may be harder to stop and could last over 20 minutes.
The English word "epistaxis" is derived from the ancient Greek word epistazo. The prefix epi means "above, upon or besides" and stazo means "to drip from the nostril"; hence, the Greek word epistazo, which means "to bleed from the nose".
There are two types of nosebleeds:
Anterior nosebleed
The bleeding originates from the lower nasal septum (nasal partition - the wall between the two nostrils). This part of the nose contains many delicate blood vessels that receive blood from the carotid arteries, two principal arteries in the front of the neck that supply blood to the head and neck. The slightest knock or bump can cause these vessels to bleed. Anterior nosebleeds are easily treated at home. This is likely to be the type of nosebleed seen in a child.
Posterior nosebleed
The bleeding originates further back and higher up the nose where artery branches supply blood to the nose, which is why it is heavier. Posterior nosebleeds are often more serious than anterior nosebleeds and may require medical attention. They are more common in adults.
What causes nosebleeds?
Causes of anterior nosebleeds
Sometimes, the cause of anterior nosebleeds is idiopathic (unknown). However, common causes include:
Blowing your nose hard - also blowing your nose too frequently.
Picking the inside of your nose - especially if this is done often, if the fingernails are long, and if the inside of the nose is already irritated or tender.
A knock or blow to the nose - could damage the delicate blood vessels of the mucous membrane.
Sinusitis - an inflammation of the sinuses (air-filled cavities of the bone and skull surrounding the nose)
A cold or flu - this could be for various reasons. Partly because people with colds and flu blow their nose more often - nose blowing raises the risk of nosebleeds. The inside of the nose may be irritated and tender during a vital infection, making it more susceptible to bleeding.
Deviated septum - when the wall separating the two nostrils is off center, or deviated.
Climate - hot climates with low humidity or changes from bitter cold to warm, dry climates can cause drying and cracking inside the nose, which can lead to a nosebleed.
High altitude - as altitude increases, the availability of oxygen decreases, making the air thinner and drier. The dryness could cause the nose to bleed.
Nasal allergies.
Excessive use of certain kinds of medications, such as anticoagulants (blood thinners) or non-steroidal anti-inflammatory drugs (NSAIDs) like Ibuprofen.
Liver disease can interfere with blood clotting and result in frequent and/or severe nosebleeds.
Excessive use of illegal drugs, such as cocaine.
Causes of posterior nosebleeds:
Hypertension (high blood pressure)
Nasal surgery (surgery of the nose)
Calcium deficiency
Exposure to chemicals that may irritate the mucous membrane
Posterior nosebleeds are sometimes symptoms of other conditions, such as blood diseases (e.g. leukemia or hemophilia) or tumors.
What are the risk factors for a nosebleed?
A risk factor is something that increases the chances of developing a disease or condition. For example, smoking increases the risk of developing lung cancer. Therefore smoking is a risk factor for lung cancer.
Common risk factors for nosebleeds are:
Infection
Self-induced minor injuries such as picking the nose
Hypertension (high blood pressure)
Alcohol abuse
Inherited bleeding disorders
Certain contact sports, such as martial arts, boxing, and rugby
What are the signs and symptoms of a nosebleed?
The main symptom of a nosebleed is blood coming out of the nose, which can range from light to heavy. The blood comes out of either nostril (usually only one nostril is affected).
If the nosebleed occurs while you are lying down, you may feel liquid in the back of your throat before the blood actually comes out of your nose. Do not swallow the blood as it could cause you to become nauseous and vomit.
Severe nosebleeds require immediate medical attention. Things to watch for include heavy bleeding, palpitations (an irregular heartbeat), swallowing large amounts of blood that cause you to vomit, shortness of breath, or turning pale.
What are the treatment options for a nosebleed?
The first step to stopping any nosebleed is always the same: stop the bleeding. This can be done by complying with the following steps:
Sit down and pinch the soft parts of your nose firmly, breathing through your mouth.
Lean forward, not backward, in order to prevent the blood from draining into your sinuses and throat, which can result in inhaling the blood or gagging.
Sit upright so that your head is higher than your heart to reduce blood pressure and consequently stop further bleeding.
Continue putting pressure on the nose, leaning forward, and sitting upright for a minimum of five minutes and up to 20 minutes so that the blood clots. If bleeding persists for more than 20 minutes, medical attention is required.
Apply an ice pack to your nose and cheek to soothe the area and try not to strain yourself for the next few days.
It is recommended that you seek medical attention if you suffer from frequent nosebleeds (it could be an indication of an underlying problem), had an injury to the head, or take anticoagulants (blood thinning medications) and the bleeding does not stop.
If your physician suspects there is an underlying cause, such as hypertension (high blood pressure), anemia, or a nasal fracture, they may run further tests, such as checking your blood pressure and pulse rate or an X-ray, before recommending a suitable treatment option.
A broken nose can permanently change the shape of your nose. If this is the case, a physician can attempt to set the nose back in place manually, but sometimes surgery is required.
There is an array of treatment options physicians have to offer. Some of them include:
Nasal packing - stuffing ribbon gauze or special nasal sponges as far back into your nose as possible, putting pressure on the source of the bleed.
Cautery - a minor procedure that cauterizes (burns) the area where the bleeding is coming from to seal it off; used if the specific blood vessel can be identified. However, the area around the cautery sometimes begins to bleed. Be sure to go over the risks and benefits with your physician.
Septal surgery - a surgical procedure to straighten a crooked septum (the wall between the two nose channels), whether it was like that from birth or from an injury. This can reduce the occurrence of nosebleeds. Your physician will be able to explain the procedure and its risks and benefits in detail.
Ligation - a "last resort" surgical procedure that involves tying the ends of the identified blood vessels causing the bleeding. Sometimes even the artery from which the blood vessels stem is tied off. If the source of the bleed is further back, more major surgery may be required. Be sure to go over details with your physician.
How can a nosebleed be prevented?
Avoid picking your nose.
Apply lubricating ointment, such as petroleum jelly (Vaseline), inside your nose; especially in children whose nosebleeds are most commonly attributed to crusting inside the nostrils.
Avoid blowing your nose too hard, or too frequently.
Use a humidifier at high altitudes or in dry climates.
If you are prescribed anticoagulants (blood-thinning medications) discuss your concerns with your physician.
To prevent recurring nosebleeds, avoid exerting or straining yourself for a minimum of one week after the previous one.
Written by Caroline Caroline Gillott
According to Medilexicon's medical dictionary, epistaxis means "Bleeding from the nose". Nosebleeds are seldom a cause for alarm but can be life threatening in rare cases.
Spontaneous nosebleeds are fairly common, especially in children. When the mucous membrane (a mucus-secreting tissue) inside the nose dries, crusts, or cracks (the skin splits open) and is then picked, it is likely to bleed.
Because the nose is full of blood vessels and is inconveniently situated in the middle of the face, any minor injury to the face can cause the nose to bleed profusely.
Nosebleeds are also common in people taking anti-coagulants (blood-thinning medications, such as Aspirin), as well as in older people whose blood may take longer to clot. If the patient is taking anti-coagulants, has hypertension (high blood pressure), or a blood-clotting disorder, the bleeding may be harder to stop and could last over 20 minutes.
The English word "epistaxis" is derived from the ancient Greek word epistazo. The prefix epi means "above, upon or besides" and stazo means "to drip from the nostril"; hence, the Greek word epistazo, which means "to bleed from the nose".
There are two types of nosebleeds:
Anterior nosebleed
The bleeding originates from the lower nasal septum (nasal partition - the wall between the two nostrils). This part of the nose contains many delicate blood vessels that receive blood from the carotid arteries, two principal arteries in the front of the neck that supply blood to the head and neck. The slightest knock or bump can cause these vessels to bleed. Anterior nosebleeds are easily treated at home. This is likely to be the type of nosebleed seen in a child.
Posterior nosebleed
The bleeding originates further back and higher up the nose where artery branches supply blood to the nose, which is why it is heavier. Posterior nosebleeds are often more serious than anterior nosebleeds and may require medical attention. They are more common in adults.
What causes nosebleeds?
Causes of anterior nosebleeds
Sometimes, the cause of anterior nosebleeds is idiopathic (unknown). However, common causes include:
Blowing your nose hard - also blowing your nose too frequently.
Picking the inside of your nose - especially if this is done often, if the fingernails are long, and if the inside of the nose is already irritated or tender.
A knock or blow to the nose - could damage the delicate blood vessels of the mucous membrane.
Sinusitis - an inflammation of the sinuses (air-filled cavities of the bone and skull surrounding the nose)
A cold or flu - this could be for various reasons. Partly because people with colds and flu blow their nose more often - nose blowing raises the risk of nosebleeds. The inside of the nose may be irritated and tender during a vital infection, making it more susceptible to bleeding.
Deviated septum - when the wall separating the two nostrils is off center, or deviated.
Climate - hot climates with low humidity or changes from bitter cold to warm, dry climates can cause drying and cracking inside the nose, which can lead to a nosebleed.
High altitude - as altitude increases, the availability of oxygen decreases, making the air thinner and drier. The dryness could cause the nose to bleed.
Nasal allergies.
Excessive use of certain kinds of medications, such as anticoagulants (blood thinners) or non-steroidal anti-inflammatory drugs (NSAIDs) like Ibuprofen.
Liver disease can interfere with blood clotting and result in frequent and/or severe nosebleeds.
Excessive use of illegal drugs, such as cocaine.
Causes of posterior nosebleeds:
Hypertension (high blood pressure)
Nasal surgery (surgery of the nose)
Calcium deficiency
Exposure to chemicals that may irritate the mucous membrane
Posterior nosebleeds are sometimes symptoms of other conditions, such as blood diseases (e.g. leukemia or hemophilia) or tumors.
What are the risk factors for a nosebleed?
A risk factor is something that increases the chances of developing a disease or condition. For example, smoking increases the risk of developing lung cancer. Therefore smoking is a risk factor for lung cancer.
Common risk factors for nosebleeds are:
Infection
Self-induced minor injuries such as picking the nose
Hypertension (high blood pressure)
Alcohol abuse
Inherited bleeding disorders
Certain contact sports, such as martial arts, boxing, and rugby
What are the signs and symptoms of a nosebleed?
The main symptom of a nosebleed is blood coming out of the nose, which can range from light to heavy. The blood comes out of either nostril (usually only one nostril is affected).
If the nosebleed occurs while you are lying down, you may feel liquid in the back of your throat before the blood actually comes out of your nose. Do not swallow the blood as it could cause you to become nauseous and vomit.
Severe nosebleeds require immediate medical attention. Things to watch for include heavy bleeding, palpitations (an irregular heartbeat), swallowing large amounts of blood that cause you to vomit, shortness of breath, or turning pale.
What are the treatment options for a nosebleed?
The first step to stopping any nosebleed is always the same: stop the bleeding. This can be done by complying with the following steps:
Sit down and pinch the soft parts of your nose firmly, breathing through your mouth.
Lean forward, not backward, in order to prevent the blood from draining into your sinuses and throat, which can result in inhaling the blood or gagging.
Sit upright so that your head is higher than your heart to reduce blood pressure and consequently stop further bleeding.
Continue putting pressure on the nose, leaning forward, and sitting upright for a minimum of five minutes and up to 20 minutes so that the blood clots. If bleeding persists for more than 20 minutes, medical attention is required.
Apply an ice pack to your nose and cheek to soothe the area and try not to strain yourself for the next few days.
It is recommended that you seek medical attention if you suffer from frequent nosebleeds (it could be an indication of an underlying problem), had an injury to the head, or take anticoagulants (blood thinning medications) and the bleeding does not stop.
If your physician suspects there is an underlying cause, such as hypertension (high blood pressure), anemia, or a nasal fracture, they may run further tests, such as checking your blood pressure and pulse rate or an X-ray, before recommending a suitable treatment option.
A broken nose can permanently change the shape of your nose. If this is the case, a physician can attempt to set the nose back in place manually, but sometimes surgery is required.
There is an array of treatment options physicians have to offer. Some of them include:
Nasal packing - stuffing ribbon gauze or special nasal sponges as far back into your nose as possible, putting pressure on the source of the bleed.
Cautery - a minor procedure that cauterizes (burns) the area where the bleeding is coming from to seal it off; used if the specific blood vessel can be identified. However, the area around the cautery sometimes begins to bleed. Be sure to go over the risks and benefits with your physician.
Septal surgery - a surgical procedure to straighten a crooked septum (the wall between the two nose channels), whether it was like that from birth or from an injury. This can reduce the occurrence of nosebleeds. Your physician will be able to explain the procedure and its risks and benefits in detail.
Ligation - a "last resort" surgical procedure that involves tying the ends of the identified blood vessels causing the bleeding. Sometimes even the artery from which the blood vessels stem is tied off. If the source of the bleed is further back, more major surgery may be required. Be sure to go over details with your physician.
How can a nosebleed be prevented?
Avoid picking your nose.
Apply lubricating ointment, such as petroleum jelly (Vaseline), inside your nose; especially in children whose nosebleeds are most commonly attributed to crusting inside the nostrils.
Avoid blowing your nose too hard, or too frequently.
Use a humidifier at high altitudes or in dry climates.
If you are prescribed anticoagulants (blood-thinning medications) discuss your concerns with your physician.
To prevent recurring nosebleeds, avoid exerting or straining yourself for a minimum of one week after the previous one.
Written by Caroline Caroline Gillott
Eisai Will Initiate First Head-to-Head Study Comparing Dacogen(R) (decitabine For Injection) And Vidaza(R) (azacitidine)
Eisai Corporation of North America announced that it plans to initiate the first clinical trial evaluating the activity of Dacogen(R) (decitabine for injection) compared to Vidaza(R) (azacitidine) in adult patients with intermediate-1, intermediate-2 or high-risk myelodysplastic syndromes (MDS), a potentially life-threatening group of bone marrow diseases that limit the production of functional blood cells. The head-to-head trial will be conducted in the United States and will directly compare Dacogen(R) to Vidaza(R) with a primary endpoint of complete response rate (including marrow complete response).
"Previous to the introduction of the hypomethylating agents, supportive care was the only treatment option for patients living with MDS," said Dr. Hagop M. Kantarjian, chairman of the Leukemia Department and professor of medicine, University of Texas M.D. Anderson Cancer Center. "This study, for the first time, will provide physicians with important information to understand how these two agents compare when treating patients with MDS, who currently have a generally poor prognosis, with life expectancies shorter than those with lung cancer."
Study Design
This randomized, multi-center, open-label study will be conducted among 228 adult patients with intermediate-1, intermediate-2 and high-risk MDS. Patients will be randomized on a 1:1 ratio to either Dacogen(R) or Vidaza(R). Each treatment arm will be stratified by IPSS risk group and type of MDS (primary vs. secondary).
The study's primary objective is to compare the complete response rates, including bone marrow response rates, for Dacogen(R) versus Vidaza(R).
"Findings from this trial could help clarify the fundamental differences between Dacogen and Vidaza and ultimately help clinicians with treatment selection," said Dr. Anastasios Raptis, co-director, Myelodysplastic Syndrome Program, attending, Stem Cell Transplant Program and clinical assistant professor of medicine, University of Pittsburgh School of Medicine. "This study takes into account recent data that suggest that treatment of patients should continue for as long as they receive clinical benefit or until their disease progresses."
Eisai is committed to a clinical development program to optimize the utility of Dacogen(R) for patients with MDS. To advance the understanding of optimal treatment for MDS, hematological malignancies and other cancers, there are currently more than 30 ongoing trials with Dacogen(R) either as a single agent or in combination with other therapies.
About MDS
Myelodysplastic syndromes, or MDS, are a group of diseases of the bone marrow characterized by the production of poorly functioning and immature blood cells. People with MDS may experience a variety of symptoms and complications, including anemia, bleeding, infection, fatigue and weakness. Those patients with high-risk MDS may experience bone marrow failure, which may lead to death from bleeding and infection. Over time, MDS can progress to acute leukemia, or AML. The Aplastic Anemia and MDS International Foundation currently estimates that up to 30,000 new cases of MDS are diagnosed annually in the United States.
About Dacogen(R)
Dacogen(R) (decitabine for injection) was approved by the U.S. Food and Drug Administration on May 2, 2006, and is indicated for treatment of patients with myelodysplastic syndromes (MDS) including previously treated and untreated, de novo and secondary MDS of all French-American-British (FAB) subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, chronic myelomonocytic leukemia), and Intermediate-1, Intermediate-2 and High-Risk International Prognostic Scoring System (IPSS) groups.
Dacogen(R) may cause fetal harm when administered to a pregnant woman. Women of childbearing potential should be advised to avoid becoming pregnant while using Dacogen(R). Men should be advised not to father a child while receiving treatment with Dacogen(R) and for two months afterwards. The most commonly occurring adverse reactions with Dacogen(R) include neutropenia (90%), thrombocytopenia (89%), anemia (82%), pyrexia (53%), fatigue (48%), nausea (42%), cough (40%), petechiae (39%), constipation (35%), and diarrhea (34%).
Please visit dacogen for full prescribing information.
About Eisai Corporation of North America
Eisai Corporation of North America is a wholly-owned subsidiary of Eisai Co., Ltd., a research-based human health care (hhc) company that discovers, develops and markets products throughout the world. Eisai focuses its efforts in three therapeutic areas: neurology, gastrointestinal disorders and oncology/critical care.
Eisai Corporation of North America supports the activities of its operating companies in North America, which include: Eisai Research Institute of Boston, Inc., a discovery operation with strong organic chemistry capabilities; Morphotek, Inc., a biopharmaceutical company specializing in the development of therapeutic monoclonal antibodies; Eisai Medical Research Inc., a clinical development group; Eisai Inc., a commercial operation with manufacturing and marketing/sales functions; and Eisai Machinery U.S.A., which markets and maintains pharmaceutical manufacturing machinery.
Eisai Inc.
dacogen
View drug information on Dacogen; Vidaza.
"Previous to the introduction of the hypomethylating agents, supportive care was the only treatment option for patients living with MDS," said Dr. Hagop M. Kantarjian, chairman of the Leukemia Department and professor of medicine, University of Texas M.D. Anderson Cancer Center. "This study, for the first time, will provide physicians with important information to understand how these two agents compare when treating patients with MDS, who currently have a generally poor prognosis, with life expectancies shorter than those with lung cancer."
Study Design
This randomized, multi-center, open-label study will be conducted among 228 adult patients with intermediate-1, intermediate-2 and high-risk MDS. Patients will be randomized on a 1:1 ratio to either Dacogen(R) or Vidaza(R). Each treatment arm will be stratified by IPSS risk group and type of MDS (primary vs. secondary).
The study's primary objective is to compare the complete response rates, including bone marrow response rates, for Dacogen(R) versus Vidaza(R).
"Findings from this trial could help clarify the fundamental differences between Dacogen and Vidaza and ultimately help clinicians with treatment selection," said Dr. Anastasios Raptis, co-director, Myelodysplastic Syndrome Program, attending, Stem Cell Transplant Program and clinical assistant professor of medicine, University of Pittsburgh School of Medicine. "This study takes into account recent data that suggest that treatment of patients should continue for as long as they receive clinical benefit or until their disease progresses."
Eisai is committed to a clinical development program to optimize the utility of Dacogen(R) for patients with MDS. To advance the understanding of optimal treatment for MDS, hematological malignancies and other cancers, there are currently more than 30 ongoing trials with Dacogen(R) either as a single agent or in combination with other therapies.
About MDS
Myelodysplastic syndromes, or MDS, are a group of diseases of the bone marrow characterized by the production of poorly functioning and immature blood cells. People with MDS may experience a variety of symptoms and complications, including anemia, bleeding, infection, fatigue and weakness. Those patients with high-risk MDS may experience bone marrow failure, which may lead to death from bleeding and infection. Over time, MDS can progress to acute leukemia, or AML. The Aplastic Anemia and MDS International Foundation currently estimates that up to 30,000 new cases of MDS are diagnosed annually in the United States.
About Dacogen(R)
Dacogen(R) (decitabine for injection) was approved by the U.S. Food and Drug Administration on May 2, 2006, and is indicated for treatment of patients with myelodysplastic syndromes (MDS) including previously treated and untreated, de novo and secondary MDS of all French-American-British (FAB) subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, chronic myelomonocytic leukemia), and Intermediate-1, Intermediate-2 and High-Risk International Prognostic Scoring System (IPSS) groups.
Dacogen(R) may cause fetal harm when administered to a pregnant woman. Women of childbearing potential should be advised to avoid becoming pregnant while using Dacogen(R). Men should be advised not to father a child while receiving treatment with Dacogen(R) and for two months afterwards. The most commonly occurring adverse reactions with Dacogen(R) include neutropenia (90%), thrombocytopenia (89%), anemia (82%), pyrexia (53%), fatigue (48%), nausea (42%), cough (40%), petechiae (39%), constipation (35%), and diarrhea (34%).
Please visit dacogen for full prescribing information.
About Eisai Corporation of North America
Eisai Corporation of North America is a wholly-owned subsidiary of Eisai Co., Ltd., a research-based human health care (hhc) company that discovers, develops and markets products throughout the world. Eisai focuses its efforts in three therapeutic areas: neurology, gastrointestinal disorders and oncology/critical care.
Eisai Corporation of North America supports the activities of its operating companies in North America, which include: Eisai Research Institute of Boston, Inc., a discovery operation with strong organic chemistry capabilities; Morphotek, Inc., a biopharmaceutical company specializing in the development of therapeutic monoclonal antibodies; Eisai Medical Research Inc., a clinical development group; Eisai Inc., a commercial operation with manufacturing and marketing/sales functions; and Eisai Machinery U.S.A., which markets and maintains pharmaceutical manufacturing machinery.
Eisai Inc.
dacogen
View drug information on Dacogen; Vidaza.
First-Ever Published Study Underscores Significant Economic Burden Of Hereditary Angioedema On Patients, Families And The Healthcare System
Dyax Corp. (NASDAQ: DYAX) announced the publication of a first-ever comprehensive examination of the economic burden associated with the treatment of acute attacks and chronic management of hereditary angioedema (HAE). The results, published today in the Annals of Allergy, Asthma, and Immunology, bring to light the substantial direct and indirect medical costs of the disease on patients, payers and society. The economic study is one component of a larger survey-based Burden of Illness (BOI) study which assessed both the economic and humanistic burden of HAE. The BOI study was conducted by Dyax in conjunction with the United States Hereditary Angioedema Association (HAEA) and United Biosource Corporation (UBC).
Monetizable and non-monetizable costs were captured in the study and highlighted HAE's costly and detrimental impact for patients, payers and society. Monetizable costs averaged $42,000 annually per HAE patient. Costs included direct costs associated with emergency care, physician visits, hospital stays, tests and procedures, and medications, as well as indirect costs such as missed work days and reduced productivity. Costs increased with disease severity. Patients who reported their most recent attack as severe amassed an estimated $96,000 in annual per patient costs. The largest cost component, accounting for approximately 48% of total costs for the average HAE patient, is emergency room visits and hospital stays for managing acute attacks.
Additional non-monetizable costs were reflected in the study yet were not part of the quantifiable analysis. These costs, which further exacerbate the economic burden on patients, payers and society, included the burden of increased depression, reduced income potential and missed opportunities. These non-monetizable costs consist of the cost of managing depression (42.5% percent of patients showed signs of at least mild depression and 19.5% reported that they were taking psychotropic or antidepressant medication), and the financial consequence of common activities being impacted such as driving, exercising and studying. Other costs that were not part of the analyses include the expense of improper procedures and medications as well as indirect costs related to non-paid caregivers. As such, these compounding costs underestimate the total costs associated with HAE.
"I have made several sacrifices in my career and personal life because of HAE. The unpredictability and frequency of my laryngeal attacks have made it impossible for me to continue working as a computer operator and, as a result, I've been out of work for twelve years," said Joan Angert, who was not officially diagnosed with HAE until nine years ago, though she suffered from its symptoms for 30 years.
HAE is a rare genetic disease characterized by unpredictable acute episodes of severe, often painful swelling affecting the extremities, abdomen and the larynx. On average, participants experienced 26.9 acute attacks per year. HAE is estimated to affect 1:10,000 to 1:50,000 individuals. More than half (56.5%) of the respondents from the study reported that they experienced painful abdominal symptoms for their most recent attacks while 24.5% reported laryngeal symptoms. Laryngeal attacks pose the greatest risk with the potential for asphyxiation.
"Our study provides a comprehensive survey of the burden patients with HAE live with," explained lead author David Wilson, MA, Assistant Professor, MGH Institute of Health Professions. "The breadth of the economic consequences highlighted in this study hopefully will raise people's understanding of the disease and inform them of the value of having new therapies available for the people with HAE."
Study Methodology
The Burden of Illness study, developed in consultation with expert health economists, HAE experts, and HAE patients, was conducted from November 2007 to January 2008. Study participants were recruited using the HAEA database of HAE patients. The study collected responses from 457 HAE patients via an Institutional Review Board-approved, web-based survey that solicited information on attack characterization, acute attack treatment, chronic disease management, impact on work and patient costs. A standardized instrument, the Work Productivity and Activity Impairment (WPAI) tool, was included to assess impact on work and productivity. Standard medical costs and U.S. average wage costs were assigned to survey items to assess direct medical and indirect costs, respectively.
About HAE
Hereditary angioedema (HAE) is a rare acute inflammatory condition characterized by episodes of severe, often painful swelling affecting the extremities, the gastrointestinal tract, the genitalia, and in the larynx. HAE is caused by low or dysfunctional levels of C1 esterase inhibitor (C1-INH), a naturally occurring molecule that inhibits plasma kallikrein, a key mediator of inflammation, and other serine proteases in the blood. HAE is estimated to affect 1:10,000 to 1:50,000 individuals. Learn more at HAEHope.
Source
Dyax
Monetizable and non-monetizable costs were captured in the study and highlighted HAE's costly and detrimental impact for patients, payers and society. Monetizable costs averaged $42,000 annually per HAE patient. Costs included direct costs associated with emergency care, physician visits, hospital stays, tests and procedures, and medications, as well as indirect costs such as missed work days and reduced productivity. Costs increased with disease severity. Patients who reported their most recent attack as severe amassed an estimated $96,000 in annual per patient costs. The largest cost component, accounting for approximately 48% of total costs for the average HAE patient, is emergency room visits and hospital stays for managing acute attacks.
Additional non-monetizable costs were reflected in the study yet were not part of the quantifiable analysis. These costs, which further exacerbate the economic burden on patients, payers and society, included the burden of increased depression, reduced income potential and missed opportunities. These non-monetizable costs consist of the cost of managing depression (42.5% percent of patients showed signs of at least mild depression and 19.5% reported that they were taking psychotropic or antidepressant medication), and the financial consequence of common activities being impacted such as driving, exercising and studying. Other costs that were not part of the analyses include the expense of improper procedures and medications as well as indirect costs related to non-paid caregivers. As such, these compounding costs underestimate the total costs associated with HAE.
"I have made several sacrifices in my career and personal life because of HAE. The unpredictability and frequency of my laryngeal attacks have made it impossible for me to continue working as a computer operator and, as a result, I've been out of work for twelve years," said Joan Angert, who was not officially diagnosed with HAE until nine years ago, though she suffered from its symptoms for 30 years.
HAE is a rare genetic disease characterized by unpredictable acute episodes of severe, often painful swelling affecting the extremities, abdomen and the larynx. On average, participants experienced 26.9 acute attacks per year. HAE is estimated to affect 1:10,000 to 1:50,000 individuals. More than half (56.5%) of the respondents from the study reported that they experienced painful abdominal symptoms for their most recent attacks while 24.5% reported laryngeal symptoms. Laryngeal attacks pose the greatest risk with the potential for asphyxiation.
"Our study provides a comprehensive survey of the burden patients with HAE live with," explained lead author David Wilson, MA, Assistant Professor, MGH Institute of Health Professions. "The breadth of the economic consequences highlighted in this study hopefully will raise people's understanding of the disease and inform them of the value of having new therapies available for the people with HAE."
Study Methodology
The Burden of Illness study, developed in consultation with expert health economists, HAE experts, and HAE patients, was conducted from November 2007 to January 2008. Study participants were recruited using the HAEA database of HAE patients. The study collected responses from 457 HAE patients via an Institutional Review Board-approved, web-based survey that solicited information on attack characterization, acute attack treatment, chronic disease management, impact on work and patient costs. A standardized instrument, the Work Productivity and Activity Impairment (WPAI) tool, was included to assess impact on work and productivity. Standard medical costs and U.S. average wage costs were assigned to survey items to assess direct medical and indirect costs, respectively.
About HAE
Hereditary angioedema (HAE) is a rare acute inflammatory condition characterized by episodes of severe, often painful swelling affecting the extremities, the gastrointestinal tract, the genitalia, and in the larynx. HAE is caused by low or dysfunctional levels of C1 esterase inhibitor (C1-INH), a naturally occurring molecule that inhibits plasma kallikrein, a key mediator of inflammation, and other serine proteases in the blood. HAE is estimated to affect 1:10,000 to 1:50,000 individuals. Learn more at HAEHope.
Source
Dyax
Vancomycin May Trigger Dangerously Low Platelet Count
The antibiotic vancomycin often used in intensive care units is considered the drug of choice for the treatment of staphylococci (staph) infections that are resistant to most other antibiotics. Researchers at the Medical College of Wisconsin in Milwaukee and the BloodCenter of Wisconsin's Blood Research Institute have linked vancomycin to an abnormal decrease in blood platelet count, a condition called thrombocytopenia. If accompanied by uncontrollable bleeding, thrombocytopenia can be fatal. The study led by Annette Von Drygalski, M.D., third year internal medicine resident, and Richard H. Aster M.D., professor of medicine at the Medical College, and senior investigator at the Blood Research Institute, appears in the New England Journal of Medicine.
Patients suspected of having thrombocytopenia, or low blood platelet count often associated with bleeding, can be tested for a special type of antibody to see if it is related to medications. For this study, the researchers obtained clinical information on 29 patients who tested positive for vancomycin-dependent platelet antibodies. The patients were seen at major U.S. hospitals.
"We found a close correlation between exposure to vancomycin, development of a vancomycin-dependent antibody, and the onset of severe thrombocytopenia accompanied by serious bleeding in most cases," Says Dr. Aster. "Three of the 29 cases described ended fatally. Serious bleeding appears to have contributed to these outcomes."
It is not widely recognized that vancomycin can cause thrombocytopenia. For that reason, the medication was continued in 15 of the 29 patients while other possible causes for the low platelet count were investigated, according to Dr. Aster. None of these patients had a rise in the platelet count until the vancomycin was discontinued and an alternative antibiotic started. The vancomycin was stopped early in the remaining 14 patients because it was suspected to be the cause of the thrombocytopenia. The platelet count of these patients rose to normal shortly thereafter.
In a separate study, the researchers found that 25 patients given vancomycin who did not develop thrombocytopenia did not develop antibodies.
"Vancomycin has been in widespread use for more than 25 years and can be a life-saving medication when used in the appropriate context," says Dr. Aster. Since only a small fraction of patients given vancomycin produce antibodies that cause thrombocytopenia, the findings should have no impact on the clinical use of vancomycin."
"Instead," he says, "clinicians administering vancomycin should be alert to the fact that it can cause severe immune thrombocytopenia and have their patient seen by a hematology consultant if they develop a low platelet count while under treatment with the drug. If there's a question, the physician should substitute another antibiotic for vancomycin for a few days to see if the platelet count improves."
Dr. Aster's team will continue to study patients with vancomycin-induced immune thrombocytopenia as they are encountered.
"The real lessons, though, will be learning more about how drugs such as vancomycin trigger the production of antibodies that destroy red and white blood cells in addition to platelets. We also hope to find out how the drugs cause this type of antibody to bind to blood cells and cause their destruction. A longer-term goal is to develop ways to identify environmental and genetic factors that predispose individuals to experience this type of drug hypersensitivity reaction," says Dr. Aster.
The work was supported by a grant from the National Heart, Lung, and Blood Institute and by the BloodCenter of Wisconsin Research Foundation.
Contact: Toranj Marphetia
Medical College of Wisconsin
Patients suspected of having thrombocytopenia, or low blood platelet count often associated with bleeding, can be tested for a special type of antibody to see if it is related to medications. For this study, the researchers obtained clinical information on 29 patients who tested positive for vancomycin-dependent platelet antibodies. The patients were seen at major U.S. hospitals.
"We found a close correlation between exposure to vancomycin, development of a vancomycin-dependent antibody, and the onset of severe thrombocytopenia accompanied by serious bleeding in most cases," Says Dr. Aster. "Three of the 29 cases described ended fatally. Serious bleeding appears to have contributed to these outcomes."
It is not widely recognized that vancomycin can cause thrombocytopenia. For that reason, the medication was continued in 15 of the 29 patients while other possible causes for the low platelet count were investigated, according to Dr. Aster. None of these patients had a rise in the platelet count until the vancomycin was discontinued and an alternative antibiotic started. The vancomycin was stopped early in the remaining 14 patients because it was suspected to be the cause of the thrombocytopenia. The platelet count of these patients rose to normal shortly thereafter.
In a separate study, the researchers found that 25 patients given vancomycin who did not develop thrombocytopenia did not develop antibodies.
"Vancomycin has been in widespread use for more than 25 years and can be a life-saving medication when used in the appropriate context," says Dr. Aster. Since only a small fraction of patients given vancomycin produce antibodies that cause thrombocytopenia, the findings should have no impact on the clinical use of vancomycin."
"Instead," he says, "clinicians administering vancomycin should be alert to the fact that it can cause severe immune thrombocytopenia and have their patient seen by a hematology consultant if they develop a low platelet count while under treatment with the drug. If there's a question, the physician should substitute another antibiotic for vancomycin for a few days to see if the platelet count improves."
Dr. Aster's team will continue to study patients with vancomycin-induced immune thrombocytopenia as they are encountered.
"The real lessons, though, will be learning more about how drugs such as vancomycin trigger the production of antibodies that destroy red and white blood cells in addition to platelets. We also hope to find out how the drugs cause this type of antibody to bind to blood cells and cause their destruction. A longer-term goal is to develop ways to identify environmental and genetic factors that predispose individuals to experience this type of drug hypersensitivity reaction," says Dr. Aster.
The work was supported by a grant from the National Heart, Lung, and Blood Institute and by the BloodCenter of Wisconsin Research Foundation.
Contact: Toranj Marphetia
Medical College of Wisconsin
AdvanDx Launches Fast, 90 Minutes Protocol For All CE-IVD Marked PNA FISH(R) Tests In Europe
AdvanDx announced that it has launched a fast, 90 minutes protocol for all CE-IVD marked PNA FISH(R) tests in Europe. The fast protocol reduces the PNA FISH turn-around time from the original 2.5 hours to 90 minutes by reducing PNA probe hybridization time from 90 minutes to 30 minutes. Clinical validation studies performed at hospitals in the United States and Europe show the two protocols to be 100% equivalent while maintaining the very high (>95%) sensitivity and specificity versus slower, conventional laboratory methods.
Since the first product launch in May 2003, AdvanDx's PNA FISH tests have provided rapid identification of bloodstream pathogens to help clinicians optimize antibiotic therapy and improve care for patients with critical infections. Clinical studies have shown that implementing PNA FISH tests reduced time to reporting of pathogen identification results by up to 48-72 hours, improved antibiotic selection for patients with bloodstream infections, reduced unnecessary antibiotic use, reduced infection related mortality rates and significantly reduced hospital bed, pharmacy and laboratory costs. (1,2,3,4) With the shortened protocol, labs will be able to provide results even faster to help clinicians further improve antibiotic prescribing and patient care.
"We are very excited to launch the shortened PNA FISH protocol in Europe," said Thais T. Johansen, President and CEO of AdvanDx. "The faster results will enable laboratories to provide this critical information sooner to clinicians, enabling them to make the most appropriate antibiotic selection and treatment decision as early as possible," Johansen concluded.
PNA FISH Diagnostic Platform Features:
-- Standard protocol with 90 min. Turn-around Time and minimal Hands-on Time
-- Close to 100% sensitivity and specificity versus conventional, slower laboratory methods
-- Molecular method requiring only a fluorescence microscope to get started
-- Identification of staphylococci, enterococci, Gram-Negative bacteria and Candida species directly from positive blood cultures
-- Fast and actionable results for 95-99% of all patients with bloodstream infections and positive blood cultures
-- Cost/Benefit and outcomes studies proving clinical utility of faster results
About PNA FISH(R)
PNA FISH tests enable microbiology labs to provide rapid and accurate identification of bloodstream pathogens directly from positive blood cultures in hours instead of days. Clinical studies show that rapid identification of bloodstream pathogens using PNA FISH tests leads to more appropriate patient therapy that saves lives and reduces unnecessary antibiotic use, patient length of stay and hospital costs.
About AdvanDx
AdvanDx is the world's leading provider of advanced molecular diagnostic products for the prevention, diagnosis and treatment of life-threatening, bacterial infections. AdvanDx's easy-to-use products provide fast and accurate results that enable dramatic improvements in patient care and help to save lives and reduce hospital costs.
AdvanDx's products employ standard laboratory techniques and equipment to reduce startup, implementation, technician and maintenance time, while providing fast results without sacrificing accuracy. Major medical centers, reference labs, government institutions and community hospitals throughout the United States, Europe and Asia rely on AdvanDx products as integral parts of their medical care.
References
1. Ther Clin Risk Manag. 2008 Jun;4(3):637-40
2. Antimicrob Agents Chemother. 2008 Oct;52(10):3558-63
3. Poster P1382. ECCMID 2008, Barcelona, Spain
4. J Clin Microbiol. 2006 Sep;44(9):3381-3
Source: AdvanDx
Since the first product launch in May 2003, AdvanDx's PNA FISH tests have provided rapid identification of bloodstream pathogens to help clinicians optimize antibiotic therapy and improve care for patients with critical infections. Clinical studies have shown that implementing PNA FISH tests reduced time to reporting of pathogen identification results by up to 48-72 hours, improved antibiotic selection for patients with bloodstream infections, reduced unnecessary antibiotic use, reduced infection related mortality rates and significantly reduced hospital bed, pharmacy and laboratory costs. (1,2,3,4) With the shortened protocol, labs will be able to provide results even faster to help clinicians further improve antibiotic prescribing and patient care.
"We are very excited to launch the shortened PNA FISH protocol in Europe," said Thais T. Johansen, President and CEO of AdvanDx. "The faster results will enable laboratories to provide this critical information sooner to clinicians, enabling them to make the most appropriate antibiotic selection and treatment decision as early as possible," Johansen concluded.
PNA FISH Diagnostic Platform Features:
-- Standard protocol with 90 min. Turn-around Time and minimal Hands-on Time
-- Close to 100% sensitivity and specificity versus conventional, slower laboratory methods
-- Molecular method requiring only a fluorescence microscope to get started
-- Identification of staphylococci, enterococci, Gram-Negative bacteria and Candida species directly from positive blood cultures
-- Fast and actionable results for 95-99% of all patients with bloodstream infections and positive blood cultures
-- Cost/Benefit and outcomes studies proving clinical utility of faster results
About PNA FISH(R)
PNA FISH tests enable microbiology labs to provide rapid and accurate identification of bloodstream pathogens directly from positive blood cultures in hours instead of days. Clinical studies show that rapid identification of bloodstream pathogens using PNA FISH tests leads to more appropriate patient therapy that saves lives and reduces unnecessary antibiotic use, patient length of stay and hospital costs.
About AdvanDx
AdvanDx is the world's leading provider of advanced molecular diagnostic products for the prevention, diagnosis and treatment of life-threatening, bacterial infections. AdvanDx's easy-to-use products provide fast and accurate results that enable dramatic improvements in patient care and help to save lives and reduce hospital costs.
AdvanDx's products employ standard laboratory techniques and equipment to reduce startup, implementation, technician and maintenance time, while providing fast results without sacrificing accuracy. Major medical centers, reference labs, government institutions and community hospitals throughout the United States, Europe and Asia rely on AdvanDx products as integral parts of their medical care.
References
1. Ther Clin Risk Manag. 2008 Jun;4(3):637-40
2. Antimicrob Agents Chemother. 2008 Oct;52(10):3558-63
3. Poster P1382. ECCMID 2008, Barcelona, Spain
4. J Clin Microbiol. 2006 Sep;44(9):3381-3
Source: AdvanDx
CMS Says It Will Review Medicare Policy On Covering Anemia Medications Linked To Side Effects
CMS on Wednesday announced plans to review Medicare coverage policies for the anemia medications Aranesp and Epogen, manufactured by Amgen, and Procrit, manufactured by Johnson & Johnson, after recent studies have linked the treatments with increased risk for serious side effects, Bloomberg/New York Times reports (Bloomberg/New York Times, 3/15). CMS will review coverage of the medications for uses other than in dialysis, as well as a "monitoring policy" that requires a reduction in Medicare reimbursements for the treatments when the red blood cell counts of beneficiaries exceed a certain level (CQ HealthBeat, 3/14). The review follows a March 9 announcement by FDA that manufacturers of the medications must include black box warnings on the labels to physicians and patients about the increased risk for serious side effects linked with the treatments. In addition, FDA advised physicians that they should use only the lowest dose of the medications necessary to avoid the need for blood transfusions caused by anemia. Leslie Norwalk, acting director of CMS, said, "We pay close attention to FDA black box warnings because the safety of our Medicare beneficiaries is paramount." She added, "We will carefully examine the effect of these labeling changes on Medicare's policies." Josh Ofman, vice president of reimbursement and payment policy at Amgen, said that review is appropriate "in light of the new FDA labeling changes" (Bloomberg/New York Times, 3/15).
"Reprinted with permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.
"Reprinted with permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.
Human Proteome Organization Honors PNNL Scientist
Laboratory and Battelle Fellow Dick Smith of the Department of Energy's Pacific Northwest National Laboratory has been recognized for his many accomplishments in pioneering the development of proteomics tools. Scientists use these instruments to study the array of proteins and related molecules that make up much of human blood and tissues.
The Human Proteome Organization, or HUPO, honored Smith with its annual Discovery Award. HUPO is an international scientific organization dedicated to promoting proteomics. As the workhorses of cells, proteins take the instructions coded in a chromosome's genes and turn them into a functioning organism. Proteomics seeks to understand what proteins are functioning in healthy tissues - and when - and how dysfunction leads to disease. Proteomics researchers want to use this information to enable both better detection of diseases and to understand what is needed to develop better cures.
In receiving this award, Smith gave a special address to the 8th Annual HUPO World Congress on Proteomics and Human Health: Environment and Disease. In his presentation, Smith described some of the proteomics developments that earned him this recognition, concluding with a description of a new platform that analyzes samples at least ten times faster than its predecessor. Smith has received dozens of patents while leading the creation of these instruments that can separate and identify proteins and other molecules with higher sensitivity, accuracy and resolution for biological and biomedical applications.
Smith leads a team of a couple dozen physicists, biochemists, engineers and computer scientists at PNNL and EMSL, DOE's Environmental Molecular Sciences Laboratory on PNNL's campus. Their instruments are based on separation methods that include liquid chromatography and ion mobility in combination with mass spectrometry.
Source:
Mary Beckman
DOE/Pacific Northwest National Laboratory
The Human Proteome Organization, or HUPO, honored Smith with its annual Discovery Award. HUPO is an international scientific organization dedicated to promoting proteomics. As the workhorses of cells, proteins take the instructions coded in a chromosome's genes and turn them into a functioning organism. Proteomics seeks to understand what proteins are functioning in healthy tissues - and when - and how dysfunction leads to disease. Proteomics researchers want to use this information to enable both better detection of diseases and to understand what is needed to develop better cures.
In receiving this award, Smith gave a special address to the 8th Annual HUPO World Congress on Proteomics and Human Health: Environment and Disease. In his presentation, Smith described some of the proteomics developments that earned him this recognition, concluding with a description of a new platform that analyzes samples at least ten times faster than its predecessor. Smith has received dozens of patents while leading the creation of these instruments that can separate and identify proteins and other molecules with higher sensitivity, accuracy and resolution for biological and biomedical applications.
Smith leads a team of a couple dozen physicists, biochemists, engineers and computer scientists at PNNL and EMSL, DOE's Environmental Molecular Sciences Laboratory on PNNL's campus. Their instruments are based on separation methods that include liquid chromatography and ion mobility in combination with mass spectrometry.
Source:
Mary Beckman
DOE/Pacific Northwest National Laboratory
Routine Blood Tests Can Provide An Early Warning For Colorectal Cancer
Anemia, a common blood disorder characterized by low hemoglobin levels, has long been associated with those suffering from colorectal cancer. But researchers at Tel Aviv University have discovered that, more than a symptom of active disease, low hemoglobin levels can actually indicate a potential for colon cancer years before it's diagnosed.
Graduate student Inbal Goldshtein, who works with Dr. Gabriel Chodick and Dr. Varda Shalev of Tel Aviv University's School of Public Health and Maccabi Healthcare Services' Department of Medical Informatics, says that paying close attention to routine blood test results can be an effective screening system for colon cancer which, when diagnosed early enough, can be treated effectively. More than 50,000 people in the U.S. will die from colon cancer in 2010. Better screening could significantly reduce those numbers, Goldshtein says.
The study, recently published in the European Journal of Cancer Prevention, shows that most patients with colon cancer have a history of consistently declining hemoglobin levels up to four years before being diagnosed with the disease. Previously, says Goldshtein, researchers only looked for a sharp decrease in hemoglobin levels as a symptom of colon cancer. But Goldshtein and her fellow researchers have discovered that it's the continuous long-term decline that may announce the onset of cancer. A declining trend of more than 0.28 grams per decilitre every six months over a four-year period was observed and may serve as a warning of illness on the horizon.
An important downward trend
Taking into account the correlation between anemia and colorectal cancer, the team was keen to discover if a decline in hemoglobin levels could be detected prior to the critical stages of the disease - something no researcher had yet attempted to quantify. Over 3,000 patients suffering from colorectal cancer participated in the study; they were compared with 10,000 control cases without colorectal cancer. Goldshtein and her fellow researchers looked at data from each participant's blood tests over a ten-year period, retrieved from the computerized database of Maccabi Healthcare Services.
Though hemoglobin levels may vary in every human being as a result of aging, a distinct trend was discovered among study participants who had been diagnosed with colorectal cancer during the study period. Approximately four years prior to their diagnoses, their blood tests began to show a continuous decline in hemoglobin levels.
For the most part, says Goldshtein, these warning signs went unnoticed. "In practice, a doctor will look at the final results, and see if the hemoglobin levels are within a normal range," she explains. "But this is not accurate enough. It is important to look at the continuing trend of each individual. If a person experiences a consistent decline relative to his own average level, it may be cause for concern."
Participants of the study with colorectal cancer experienced a sharp decline in hemoglobin levels, but because the declines did not put them outside the normal range, no red flags were raised.
A new algorithm for the average physical
The benefit of this screening process is that can be part of an average physical. Current testing for colorectal cancer is often expensive and unpleasant. There is also a very low compliance rate among patients, she adds.
The next step, says Dr. Shalev, is to create an algorithm which will automatically detect suspicious declines in hemoglobin levels, advising physicians to send their patients for further testing. Ideally, she notes, the Tel Aviv University team will develop a computer program that will display warnings when there is cause for concern.
Source:
George Hunka
American Friends of Tel Aviv University
Graduate student Inbal Goldshtein, who works with Dr. Gabriel Chodick and Dr. Varda Shalev of Tel Aviv University's School of Public Health and Maccabi Healthcare Services' Department of Medical Informatics, says that paying close attention to routine blood test results can be an effective screening system for colon cancer which, when diagnosed early enough, can be treated effectively. More than 50,000 people in the U.S. will die from colon cancer in 2010. Better screening could significantly reduce those numbers, Goldshtein says.
The study, recently published in the European Journal of Cancer Prevention, shows that most patients with colon cancer have a history of consistently declining hemoglobin levels up to four years before being diagnosed with the disease. Previously, says Goldshtein, researchers only looked for a sharp decrease in hemoglobin levels as a symptom of colon cancer. But Goldshtein and her fellow researchers have discovered that it's the continuous long-term decline that may announce the onset of cancer. A declining trend of more than 0.28 grams per decilitre every six months over a four-year period was observed and may serve as a warning of illness on the horizon.
An important downward trend
Taking into account the correlation between anemia and colorectal cancer, the team was keen to discover if a decline in hemoglobin levels could be detected prior to the critical stages of the disease - something no researcher had yet attempted to quantify. Over 3,000 patients suffering from colorectal cancer participated in the study; they were compared with 10,000 control cases without colorectal cancer. Goldshtein and her fellow researchers looked at data from each participant's blood tests over a ten-year period, retrieved from the computerized database of Maccabi Healthcare Services.
Though hemoglobin levels may vary in every human being as a result of aging, a distinct trend was discovered among study participants who had been diagnosed with colorectal cancer during the study period. Approximately four years prior to their diagnoses, their blood tests began to show a continuous decline in hemoglobin levels.
For the most part, says Goldshtein, these warning signs went unnoticed. "In practice, a doctor will look at the final results, and see if the hemoglobin levels are within a normal range," she explains. "But this is not accurate enough. It is important to look at the continuing trend of each individual. If a person experiences a consistent decline relative to his own average level, it may be cause for concern."
Participants of the study with colorectal cancer experienced a sharp decline in hemoglobin levels, but because the declines did not put them outside the normal range, no red flags were raised.
A new algorithm for the average physical
The benefit of this screening process is that can be part of an average physical. Current testing for colorectal cancer is often expensive and unpleasant. There is also a very low compliance rate among patients, she adds.
The next step, says Dr. Shalev, is to create an algorithm which will automatically detect suspicious declines in hemoglobin levels, advising physicians to send their patients for further testing. Ideally, she notes, the Tel Aviv University team will develop a computer program that will display warnings when there is cause for concern.
Source:
George Hunka
American Friends of Tel Aviv University
Seattle Genetics And Millennium Complete Enrollment Of Brentuximab Vedotin (SGN-35) Phase II ALCL Trial
Seattle Genetics, Inc. (Nasdaq: SGEN) and Millennium: The Takeda Oncology Company, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited (TSE:4502), today announced that they have completed enrollment of a phase II clinical trial of brentuximab vedotin (SGN-35) for relapsed or refractory systemic anaplastic large cell lymphoma (ALCL). Brentuximab vedotin is an antibody-drug conjugate (ADC) targeted to CD30, which is highly expressed on ALCL cells.
"This phase II trial enrolled in less than a year, driven by strong interest among clinical investigators and the ALCL patient community," said Thomas C. Reynolds, M.D., Ph.D., Chief Medical Officer of Seattle Genetics. "We anticipate preliminary data from this trial will be available in the second half of 2010, which will guide the next steps towards our goal of bringing this promising ADC to ALCL patients. We believe that systemic ALCL may offer an additional registration pathway for brentuximab vedotin."
"The quick rate of enrollment in this trial attests to the high unmet need for innovative new therapies for patients with ALCL," said Nancy Simonian, M.D., Chief Medical Officer of Millennium. "Brentuximab vedotin has the potential to provide an improvement in patient care, which is our primary goal, and is another step toward global oncology leadership for Millennium."
The phase II trial, which was initiated in June 2009, is a single-agent, single-arm study evaluating 55 patients with relapsed or refractory systemic ALCL. Patients receive 1.8 milligrams per kilogram of brentuximab vedotin every three weeks for up to approximately one year. The primary endpoint of the study is objective response rate determined by independent review. Secondary endpoints include duration of response, progression-free survival, overall survival and tolerability.
Of seven systemic ALCL patients treated with brentuximab vedotin in phase I clinical trials, six (86 percent) achieved a complete remission. Brentuximab vedotin was generally well-tolerated in these studies. The majority of adverse events were Grade 1 and 2, with the most common being fatigue, fever, peripheral neuropathy, diarrhea and nausea.
About Brentuximab Vedotin
Brentuximab vedotin is an ADC comprising an anti-CD30 antibody attached by an enzyme cleavable linker to a potent, synthetic drug payload, monomethyl auristatin E (MMAE), using Seattle Genetics' proprietary technology. The ADC is designed to be stable in the bloodstream, but to release MMAE upon internalization into CD30-expressing tumor cells, resulting in targeted cell-killing.
Seattle Genetics is developing brentuximab vedotin in collaboration with Millennium, under which Seattle Genetics has U.S. and Canadian development and commercialization rights and the Takeda Group has rights to develop and commercialize brentuximab vedotin in the rest of the world. Seattle Genetics and the Takeda Group are funding joint development costs for brentuximab vedotin on a 50:50 basis, except in Japan where the Takeda Group will be solely responsible for development costs.
Under the collaboration, Seattle Genetics and Millennium are conducting a pivotal trial of brentuximab vedotin for relapsed and refractory Hodgkin lymphoma under a Special Protocol Assessment (SPA) with the U.S. Food and Drug Administration (FDA). The pivotal trial was also discussed with the European Medicines Agency during the process of obtaining EU Centralized Scientific Advice on the brentuximab vedotin development program. Top-line data from the pivotal trial are expected in the second half of 2010. In addition, the companies are conducting a phase III clinical trial (the AETHERA trial) for patients at high risk of residual Hodgkin lymphoma following autologous stem cell transplant, a phase II retreatment trial for relapsed patients who previously responded to brentuximab vedotin, and a phase I combination trial for front-line treatment of Hodgkin lymphoma.
About ALCL
Lymphoma is a general term for a group of cancers that originate in the lymphatic system. There are two major categories of lymphoma: Hodgkin lymphoma and non-Hodgkin lymphoma. ALCL is a generally aggressive type of T-cell non-Hodgkin lymphoma that expresses CD30. Although front-line combination chemotherapy can result in durable responses, ALCL patients who relapse or are refractory to front-line treatment have few therapeutic options, representing a significant unmet medical need.
About Seattle Genetics
Seattle Genetics is a clinical stage biotechnology company focused on the development and commercialization of monoclonal antibody-based therapies for the treatment of cancer and autoimmune disease. The company's lead product candidate, brentuximab vedotin, is in a pivotal trial under an SPA with the FDA. Brentuximab vedotin is being developed in collaboration with Millennium: The Takeda Oncology Company. In addition, Seattle Genetics has four other product candidates in ongoing clinical trials: lintuzumab (SGN-33), dacetuzumab (SGN-40), SGN-70 and SGN-75. Seattle Genetics has collaborations for its ADC technology with a number of leading biotechnology and pharmaceutical companies, including Bayer, Celldex Therapeutics, Daiichi Sankyo, Genentech, GlaxoSmithKline, MedImmune, a subsidiary of AstraZeneca, Millennium: The Takeda Oncology Company and Progenics, as well as an ADC co-development agreement with Agensys, an affiliate of Astellas. More information can be found here.
Source
Millennium
"This phase II trial enrolled in less than a year, driven by strong interest among clinical investigators and the ALCL patient community," said Thomas C. Reynolds, M.D., Ph.D., Chief Medical Officer of Seattle Genetics. "We anticipate preliminary data from this trial will be available in the second half of 2010, which will guide the next steps towards our goal of bringing this promising ADC to ALCL patients. We believe that systemic ALCL may offer an additional registration pathway for brentuximab vedotin."
"The quick rate of enrollment in this trial attests to the high unmet need for innovative new therapies for patients with ALCL," said Nancy Simonian, M.D., Chief Medical Officer of Millennium. "Brentuximab vedotin has the potential to provide an improvement in patient care, which is our primary goal, and is another step toward global oncology leadership for Millennium."
The phase II trial, which was initiated in June 2009, is a single-agent, single-arm study evaluating 55 patients with relapsed or refractory systemic ALCL. Patients receive 1.8 milligrams per kilogram of brentuximab vedotin every three weeks for up to approximately one year. The primary endpoint of the study is objective response rate determined by independent review. Secondary endpoints include duration of response, progression-free survival, overall survival and tolerability.
Of seven systemic ALCL patients treated with brentuximab vedotin in phase I clinical trials, six (86 percent) achieved a complete remission. Brentuximab vedotin was generally well-tolerated in these studies. The majority of adverse events were Grade 1 and 2, with the most common being fatigue, fever, peripheral neuropathy, diarrhea and nausea.
About Brentuximab Vedotin
Brentuximab vedotin is an ADC comprising an anti-CD30 antibody attached by an enzyme cleavable linker to a potent, synthetic drug payload, monomethyl auristatin E (MMAE), using Seattle Genetics' proprietary technology. The ADC is designed to be stable in the bloodstream, but to release MMAE upon internalization into CD30-expressing tumor cells, resulting in targeted cell-killing.
Seattle Genetics is developing brentuximab vedotin in collaboration with Millennium, under which Seattle Genetics has U.S. and Canadian development and commercialization rights and the Takeda Group has rights to develop and commercialize brentuximab vedotin in the rest of the world. Seattle Genetics and the Takeda Group are funding joint development costs for brentuximab vedotin on a 50:50 basis, except in Japan where the Takeda Group will be solely responsible for development costs.
Under the collaboration, Seattle Genetics and Millennium are conducting a pivotal trial of brentuximab vedotin for relapsed and refractory Hodgkin lymphoma under a Special Protocol Assessment (SPA) with the U.S. Food and Drug Administration (FDA). The pivotal trial was also discussed with the European Medicines Agency during the process of obtaining EU Centralized Scientific Advice on the brentuximab vedotin development program. Top-line data from the pivotal trial are expected in the second half of 2010. In addition, the companies are conducting a phase III clinical trial (the AETHERA trial) for patients at high risk of residual Hodgkin lymphoma following autologous stem cell transplant, a phase II retreatment trial for relapsed patients who previously responded to brentuximab vedotin, and a phase I combination trial for front-line treatment of Hodgkin lymphoma.
About ALCL
Lymphoma is a general term for a group of cancers that originate in the lymphatic system. There are two major categories of lymphoma: Hodgkin lymphoma and non-Hodgkin lymphoma. ALCL is a generally aggressive type of T-cell non-Hodgkin lymphoma that expresses CD30. Although front-line combination chemotherapy can result in durable responses, ALCL patients who relapse or are refractory to front-line treatment have few therapeutic options, representing a significant unmet medical need.
About Seattle Genetics
Seattle Genetics is a clinical stage biotechnology company focused on the development and commercialization of monoclonal antibody-based therapies for the treatment of cancer and autoimmune disease. The company's lead product candidate, brentuximab vedotin, is in a pivotal trial under an SPA with the FDA. Brentuximab vedotin is being developed in collaboration with Millennium: The Takeda Oncology Company. In addition, Seattle Genetics has four other product candidates in ongoing clinical trials: lintuzumab (SGN-33), dacetuzumab (SGN-40), SGN-70 and SGN-75. Seattle Genetics has collaborations for its ADC technology with a number of leading biotechnology and pharmaceutical companies, including Bayer, Celldex Therapeutics, Daiichi Sankyo, Genentech, GlaxoSmithKline, MedImmune, a subsidiary of AstraZeneca, Millennium: The Takeda Oncology Company and Progenics, as well as an ADC co-development agreement with Agensys, an affiliate of Astellas. More information can be found here.
Source
Millennium
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