DOR BioPharma, Inc. (OTCBB: DORB) (DOR or the Company) announced that data from its pivotal Phase 3 and supportive Phase 2 clinical trials using orBec(r) (oral beclomethasone dipropionate, or BDP) to treat gastrointestinal Graft-versus-Host disease (GI GVHD) have been pre-published this afternoon in the online edition of Blood, the peer-reviewed Journal of the American Society of Hematology, as a First Edition paper, including long-term survival analyses from these two randomized, double-blinded, placebo-controlled trials not previously made public.В Lead author of the study, entitled "A Randomized, Placebo-controlled Trial of Oral Beclomethasone Dipropionate as a Prednisone-Sparing Therapy for Gastrointestinal Graft-versus-Host Disease," is David M. Hockenbery, M.D., Member of the Clinical Research Division, Fred Hutchinson Cancer Research Center and Professor of Medicine, University of Washington School of Medicine, both located in Seattle, Washington.В The full article is available online at bloodjournal.
The Blood paper covers comprehensive results from two studies:В В DOR's 129-patient pivotal Phase 3, randomized, double-blinded, placebo-controlled multi-center clinical trial of orBec(r) conducted at 16 leading bone marrow/stem cell transplant centers in the U.S. and France; and survival data from its 60-patient Phase 2, randomized, double-blinded, placebo-controlled clinical trial conducted at the Fred Hutchinson Cancer Research Center.
Comprehensive Long-Term Mortality Results
Among the new data reported today, orBec(r) showed continued survival benefit when compared to placebo one year after randomization in the pivotal Phase 3 trial.В Overall, 18 patients (29%) in the orBec(r) group and 28 patients (42%) in the placebo group died within one year of randomization (46% reduction in mortality, hazard ratio 0.54, 95% CI: 0.30, 0.99, p=0.04, stratified log-rank test).В Results from the Phase 2 trial also demonstrated enhanced long-term survival benefit with orBec(r) versus placebo.В In that study, at one year after randomization, 6 of 31 patients (19%) in the orBec(r) group while 9 of 29 patients (31%) in the placebo group had died (45% reduction in mortality, p=0.26).В Pooling the survival data from both trials demonstrated that the survival benefit of orBec(r) treatment was sustained long after orBec(r) was discontinued and extended well beyond 3 years after the transplant.В As of September 25, 2005, median follow-up of patients in the two trials was 3.5 years (placebo patients) and 3.6 years (orBec(r) patients), with a range of 10.6 months to 11.1 years.В The risk of mortality was 37% lower for patients randomized to orBec(r) compared with placebo (hazard ratio 0.63, p=0.03, stratified log-rank test).
"This is an important, validating milestone for DOR and its orBec(r) program. В Publication of these data in Blood, one of the most prominent peer-review journals in hematology, further documents the strong safety profile and long-term survival benefit of orBec(r) in theВ treatment of GI GVHD," stated Christopher J. Schaber, Ph.D., President and Chief Executive Officer of DOR BioPharma.В "It is this comprehensive data package that is at the core of our regulatory filings with both the U.S. Food and Drug Administration and the European Medicines Evaluation Agency.В We remain extremely confident on the impact orBec(r) can have on patients undergoing hematopoietic stem cell transplant and look forward to continued interactions with FDA and the EMEA regarding its potential regulatory approval."
200 Days Post Transplant Mortality Results
Number of patients randomized
Phase 3 trial
orBec(r) 62
Pacebo 67
Phase 2 trial
orBec(r) 31
Pacebo 29
Number (%) who died
Phase 3 trial
orBec(r) 5 (8%)
Pacebo 16 (24%)
Phase 2 trial
orBec(r) 3 (10%)
Pacebo 6 (21%)
Hazard ratio (95% confidence interval)
Phase 3 trial
orBec(r) 0.33
Pacebo (0.12, 0.89)
Phase 2 trial
orBec(r) 0.47
Pacebo (0.12, 1.87)
Death with infection*
Phase 3 trial
orBec(r) 3 (5%)
Pacebo 9 (13%)
Phase 2 trial
orBec(r) 2 (6%)
Pacebo 5 (17%)
Death with relapse*
Phase 3 trial
orBec(r) 3 (5%)
Pacebo 9 (13%)
Phase 2 trial
orBec(r) 1 (3%)
Pacebo 4 (14%)
*Some patients died with both infection and relapse of their underlying malignancy.
In the pivotal Phase 3 clinical trial, survival at the pre-specified endpoint of 200 days post-transplant showed a clinically meaningful and statistically significant result.В According to the manuscript, "the risk of mortality during the 200-day post-transplant period was 67% lower with orBec(r) treatment compared to placebo treatment (hazard ratio 0.33; 95% CI: 0.12, 0.89; p=0.03, Wald chi-square test)."В Although orBec(r) did not achieve statistical significance in the primary endpoint of its pivotal trial, namely time to treatment failure through Day 50 (p=0.1177), orBec(r) did achieve statistical significance in other key outcomes such as reduction in the risk of treatment failure through Day 80 (p=0.0226) and, most importantly, demonstrated a statistically significant long-term survival advantage compared with placebo. В The most common proximate causes of death by transplant day-200 were relapse of the underlying malignancy and infection.В Relapse of the hematologic malignancy had contributed to the deaths of 9/67 patients (13.4%) in the placebo arm and 3/62 patients (4.8%) in the BDP arm. В Infection contributed to the deaths of 9/67 patients (13.4%) in the placebo arm and 3/62 (4.8%) in the BDP arm. В Acute or chronic GVHD was the proximate cause of death in 3/67 patients (4.5%) in the placebo arm and in 1/62 (1.6%) in the BDP arm.
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A retrospective analysis of survival at 200 days post-transplant in the supportive Phase 2 clinical trial showed consistent response rates with the pivotal Phase 3 trial; three patients (10%) who had been randomized to orBec(r) had died, compared with six deaths (21%) among patients who had been randomized to placebo, leading to a reduced hazard of day-200 mortality, although not statistically significantly different.В Detailed analysis of the likely proximate cause of death showed that mortality with infection or with relapse of underlying malignancy were both reduced in the same proportion after treatment with orBec(r) compared to placebo.В В By transplant day-200, relapse of hematologic malignancy had contributed to the deaths of 1 of 31 patients (3%) in the orBec(r) arm and 4 of 29 patients (14%) in the placebo arm.В Infection contributed to the deaths of 2 of 31 patients (6%) in the orBec(r) arm and 5 of 29 patients (17%) in the placebo arm.
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Safety and Adverse Events
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The frequencies of severe adverse events, adverse events related to study drug, and adverse events resulting in study drug discontinuation were all comparable to that of the placebo group in both trials.В Patients who remained on orBec(r) until Day 50 in the pivotal study had a higher likelihood of having biochemical evidence of abnormal HPA function compared to patients on placebo.В
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Commenting on the clinical utility and safety profile of orBec(r), Dr. Hockenbery stated, "Two randomized trials have shown that orBec(r) prevents relapses of acute GI GVHD after accelerated withdrawal of prednisone therapy.В The effect is durable even following discontinuation of orBec(r). Both trials showed a consistent survival benefit of orBec(r), demonstrating that the ability to reduce systemic steroid exposure while maintaining remission of GVHD is associated with better clinical outcomes. We hypothesize that topical therapy with orBec(r) improved survival by limiting GVHD-related gastrointestinal epithelial injury, preserving the mucosal barrier, reducing the need for prolonged systemic glucocorticoid treatment, and reducing the frequency of life-threatening infections."
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orBec(r) Submitted for Approval
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All of the data published today were included in the Company's New Drug Application ("NDA") filed with the U.S. Food and Drug Application ("FDA"), and the Marketing Authorization Application ("MAA") filed with the European Medicines Evaluation Agency ("EMEA").В Both health authorities have accepted the filings for review.В The FDA has said it will respond to DOR's NDA by July 21, 2007 under PDUFA guidelines.
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About GI GVHD
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GVHD is a debilitating and painful disease. В It is a common disorder among immunocompromised cancer patients after receiving allogeneic stem cell or bone marrow transplants.В Unlike organ transplants where the patient's body may reject the organ, in GVHD it is the donor cells that begin to attack the patient's body - most frequently the gut, liver and skin.В Patients with mild-to-moderate GI GVHD typically develop symptoms of anorexia, nausea, vomiting and diarrhea.В If left untreated, GI GVHD can progress to ulcerations in the lining of the GI tract, and in its most severe form, can be fatal.
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orBec(r) is a two-tablet system containing the highly-potent, topically-active corticosteroid beclomethasone dipropionate, and is designed to specifically target and treat upper and lower GI GVHD with reduced systemic immunosuppressive side effects.В Systemic immunosuppressive agents such as prednisone, which are the current standard treatments for GI GVHD, are associated with high mortality rates due to infection and debility.В Further, these drugs have not been approved for treating GI GVHD in the European Union or in the U.S., but rather are used off-label as investigational therapies for this indication.
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About Allogeneic Bone Marrow/Stem Stem Cell Transplantation (HSCT)
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Allogeneic hematopoietic stem cell transplantation ("HSCT") is considered a potentially curative option for many leukemias as well as other forms of blood cancer.В In an allogeneic HSCT procedure, hematopoietic stem cells are harvested from a closely matched relative or unrelated person, and are transplanted into the patient following either high-dose chemotherapy or intense immunosuppressive conditioning therapy.В The curative potential of allogeneic HSCT is now partly attributed to the so-called graft-versus-leukemia ("GVL") or graft-versus-tumor ("GVT") effects of the newly transplanted donor cells to recognize and destroy malignant cells in the recipient patient.
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The use of allogeneic HSCT has grown substantially over the last decade due to advances in human immunogenetics, the establishment of unrelated donor programs, the use of cord blood as a source of hematopoietic stem cells and the advent of non-myeloablative conditioning regimens ("mini-transplants") that avoid the side effects of high-dose chemotherapy.В Based on the latest statistics available, it is estimated that there are more than 10,000 HSCT procedures annually in the U.S. and a comparable number in Europe.В Estimates as to the current annual rate of increase in these procedures are as high as 20%.В High rates of morbidity and mortality occur in this patient population.В Clinical trials are also underway testing allogeneic HSCT for treatment of some metastatic solid tumors such as breast cancer, renal cell carcinoma, melanoma and ovarian cancer. Allogeneic transplants have also been used as curative therapy for several genetic disorders, including immunodeficiency syndromes, inborn errors of metabolism, thalassemia and sickle cell disease.В The primary toxicity of allogeneic HSCT, however, is GVHD in which the newly transplanted donor cells damage cells in the recipient's gastrointestinal tract, liver and skin.
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About orBec(r)
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orBec(r) represents a first-of-its-kind oral, locally acting therapy tailored to treat the gastrointestinal manifestation of GVHD, the organ system where GVHD is most frequently encountered and highly problematic.В orBec(r), if approved by the EMEA and the FDA, would be the first oral formulation of beclomethasone dipropionate ("BDP") available in the European Union and the United States, respectively.В orBec(r) is intended to reduce the need for systemic immunosuppressive drugs to treat GI GVHD.В BDP is a highly-potent, topically-active corticosteroid that has a local effect on inflamed tissue. BDP has been marketed in the U.S. and worldwide since the early 1970's as the active pharmaceutical ingredient in a nasal spray and in a metered dose inhaler for the treatment of patients with allergic rhinitis and asthma.В orBec(r) is formulated for oral administration as a single product consisting of two tablets; one tablet is intended to release BDP in the proximal portions of the GI tract and the other tablet is intended to release BDP in the more distal portions of the GI tract.В В В
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In addition to issued patents and pending worldwide patent applications held by or exclusively licensed to DOR, orBec(r) also benefits from orphan drug designations in the U.S. and in Europe for the treatment of GI GVHD, which provide for 7 and 10 years of post-approval market exclusivity, respectively.
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About DOR BioPharma, Inc.
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DOR BioPharma, Inc. is a biopharmaceutical company developing products to treat life-threatening side effects of cancer treatments and serious gastrointestinal diseases, and vaccines for certain bioterrorism agents. DOR's lead product, orBec(r) (oral beclomethasone dipropionate), is a potent, locally-acting corticosteroid being developed for the treatment of GI GVHD, a common and potentially life-threatening complication of bone marrow transplantation.В DOR has filed an NDA with the FDA for the treatment of GI GVHD, and has received an FDA PDUFA date of July 21, 2007.В В An MAA with the EMEA for orBec(r) has also been filed and validated.В orBec(r) may also have application in treating other gastrointestinal disorders characterized by severe inflammation.В
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Through its Biodefense Division, DOR is developing biomedical countermeasures pursuant to the recently enacted Project BioShield Act of 2004. DOR's biodefense products in development are recombinant subunit vaccines designed to protect against the lethal effects of exposure to ricin toxin and botulinum toxin. The ricin toxin vaccine, RiVaxTM, has been evaluated successfully in a Phase 1 clinical trial in normal volunteers.
For further information regarding DOR BioPharma, please visit the Company's website located at dorbiopharma.
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This press release contains forward-looking statements, within the meaning of Section 21E of the Securities Exchange Act of 1934, that reflect DOR BioPharma, Inc.'s current expectations about its future results, performance, prospects and opportunities, including statements regarding the potential use of orBec(r) for the treatment of gastrointestinal GVHD and the prospects for regulatory filings for orBec(r). Where possible, DOR has tried to identify these forward-looking statements by using words such as "anticipates", "believes", "intends", or similar expressions. These statements are subject to a number of risks, uncertainties and other factors that could cause actual events or results in future periods to differ materially from what is expressed in, or implied by, these statements. DOR cannot assure you that it will be able to successfully develop or commercialize products based on its technology, including orBec(r), particularly in light of the significant uncertainty inherent in developing vaccines against bioterror threats, manufacturing and conducting preclinical and clinical trials of vaccines, and obtaining regulatory approvals, that its technologies will prove to be safe and effective, that its cash expenditures will not exceed projected levels, that it will be able to obtain future financing or funds when needed, that product development and commercialization efforts will not be reduced or discontinued due to difficulties or delays in clinical trials or due to lack of progress or positive results from research and development efforts, that it will be able to successfully obtain any further grants and awards, maintain its existing grants which are subject to performance, enter into any biodefense procurement contracts with the U.S. Government or other countries, that the U.S. Congress may not pass any legislation that would provide additional funding for the Project BioShield program, that it will be able to patent, register or protect its technology from challenge and products from competition or maintain or expand its license agreements with its current licensors, or that its business strategy will be successful. Important factors which may affect the future use of orBec(r) for gastrointestinal GVHD include the risks that: because orBec(r) did not achieve statistical significance in its primary endpoint in the pivotal Phase III clinical study (i.e. a p-value of less than or equal to 0.05), the FDA may not consider orBec(r) approvable based upon existing studies, orBec(r) may not show therapeutic effect or an acceptable safety profile in future clinical trials, if required, or could take a significantly longer time to gain regulatory approval than DOR expects or may never gain approval; DOR is dependent on the expertise, effort, priorities and contractual obligations of third parties in the clinical trials, manufacturing, marketing, sales and distribution of its products; or orBec(r) may not gain market acceptance; and others may develop technologies or products superior to orBec(r).В These and other factors are described from time to time in filings with the Securities and Exchange Commission, including, but not limited to, DOR's most recent reports on Form 10-QSB and Form 10-KSB. DOR assumes no obligation to update or revise any forward-looking statements as a result of new information, future events, and changes in circumstances or for any other reason.
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