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Graft versus host disease

Graft-versus-host disease is a common complication of allogeneic bone marrow transplantation. After bone marrow transplantation, T cells present in the graft, either as contaminants or intentionally introduced into the host, attack the tissues of the transplant recipient. Graft-versus-host disease can occur even when HLA-identical siblings are the donors. HLA-identical siblings or HLA-identical unrelated donors (called a minor mismatch as opposed to differences in the HLA antigens, which constitute a major mismatch) often still have genetically different proteins that can be presented on the MHC. more...

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DOR BioPharma, Inc. Announces Top-Line Results of Pivotal Phase III Clinical Trial of orBec for Intestinal Graft-versus-Host Disease
From Business Wire, 12/30/04

MIAMI -- orBec(R) Demonstrates Highly Statistically Significant Reduction in Mortality and Positive Trend in Primary Endpoint

DOR BioPharma, Inc. (AMEX:DOR) ("DOR" or the "Company") announced the top-line results of its multi-center, pivotal Phase III clinical trial of orBec(R) (oral beclomethasone dipropionate) for the treatment of intestinal Graft-versus-Host Disease (iGVHD).

About Intestinal Graft-versus-Host Disease (iGVHD)

iGVHD is a life threatening condition that is one of the most common causes for the failure of bone marrow transplant procedures. These procedures are being increasingly utilized to treat leukemia and other cancer patients with the prospect of eliminating residual disease and reducing the likelihood of relapse. 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. orBec(R) is intended to reduce the need for systemic immunosuppressives to treat iGVHD. Currently approved systemic immunosuppressives utilized to control iGVHD substantially inhibit the highly desirable graft-versus-leukemia (GVL) effect of bone marrow transplants, leading to high rates of aggressive forms of relapse, as well as substantial rates of mortality due to opportunistic infection.

Study Design

One hundred and twenty-nine (129) post-bone marrow transplant patients presenting with Grade II iGVHD were enrolled in the randomized, double-blind, placebo-controlled, multi-center clinical trial, which was conducted at 16 bone marrow transplant centers in the United States and France. All patients in the Phase III clinical trial were initially treated with constant daily high dose (1-2 mg/kg) prednisone, which is the current standard therapy, in combination with an oral dose of either orBec(R) (8mg/day) or placebo for the first 10 days. On day 10, if patients were responding to treatment, the high dose prednisone was rapidly tapered and patients continued to receive either orBec(R) or placebo orally for an additional forty days. The primary endpoint of the study was a comparison between the two treatment arms of the time to treatment failure, defined as the need for additional therapies due to uncontrolled signs or symptoms of GVHD. Secondary endpoints in the study included a comparison of the proportion of treatment failures and clinical scores at 10 Days, 30 Days, 50 Days, 60 Days and 80 Days post-randomization, a comparison of cumulative exposure to systemic steroids, as well as a comparison of mortality at Day 200 post-transplant.

Time to Treatment Failure

While orBec(R) did not achieve statistical significance in its primary endpoint of time to treatment failure through Day 50 (p-value 0.1177), orBec(R) did achieve statistical significance in its secondary endpoint of time to treatment failure through Day 80 (p-value 0.0226). The Company believes that the p-value of 0.1177 achieved in the primary endpoint through Day 50 is primarily due to a higher than expected rate of treatment failures during days 0-10 of the study. During such period, patients were receiving high dose prednisone (1-2mg/kg/day) plus either orBec(R) (8mg/day) or placebo. For purposes of the study, patients that did not begin the rapid taper of high dose prednisone on Day 10 as called for by the regimen were deemed treatment failures for all purposes, including the calculation of statistical significance of time to treatment failure at Day 50. The Company intends to further analyze the Day 0-10 treatment failure group and the statistical impact of this group on the primary endpoint of time to treatment failure at Day 50 and discuss the results of this analysis with the FDA. Encouragingly, the treatment failure rate at Day 50 approached statistical significance (p-value 0.0515). In addition, the secondary endpoint of time to treatment failure at Day 80, as well the treatment failure rate at Day 80, each achieved statistical significance (p-values 0.0226 and 0.0048, respectively).

orBec(R) Demonstrates Highly Statistically Significant Reduction in Mortality

Perhaps of greatest clinical relevance, orBec(R) demonstrated a 70% reduction in mortality, registering only 5 (8%) deaths during the prospectively defined Day 200 post-transplant period versus 17 (26%) deaths for the placebo group (p-value 0.006). Based upon separate analysis conducted by the Company, there is also a statistically significant correlation between treatment failure and mortality.

Prior Study Results

orBec(R) was previously tested in a randomized, double blind, placebo-controlled Phase II study (Gastroenterology, 1998; 115: 28-35). In that study, 60 patients with iGVHD were randomized to receive conventional prednisone therapy plus either orBec(R) or placebo. Initial responders continued to take orBec(R) or placebo for an additional 20 days, during which time the conventional therapy was rapidly tapered. The primary endpoint for this study was the clinically relevant determination of whether iGVHD patients at Day 30 were or were not able to consume at least 70% of their daily caloric intake by mouth, as compared to intravenous parenteral nutrition administered in the hospital. The treatment response at Day 30 was 22 of 31 (71%) vs. 12 of 29 (41%) in the orBec(R) and placebo groups respectively, achieving a statistically significant p-value of 0.02.


George B. McDonald, MD, Head of the Gastroenterology/Hepatology Section at the Fred Hutchinson Cancer Research Center, inventor of orBec(R) and a consultant to DOR stated, "We now have the results from two randomized, double blind, placebo-controlled trials of orBec(R) in patients with iGVHD, and both provide convincing evidence of effectiveness. The survival data in the current study is of particular interest, suggesting that avoidance of high-dose systemic immunosuppression in favor of topical immunosuppressive therapy for iGVHD may reduce mortality after transplant. orBec(R) has the potential to be an extraordinarily useful addition to the armamentarium of post-transplant immunosuppressive care, as it offers efficacy with very little toxicity."

DOR plans to meet with the FDA to determine next steps and plans to update the public and investors regarding the outcome of this proposed meeting.

orBec(R), if approved by the FDA, would be the first oral formulation of beclomethasone dipropionate (BDP) available in the United States. 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 a nasal spray and in a metered dose inhaler for the treatment of patients with allergic rhinitis and asthma. orBec(R) is delivered to the gastrointestinal (GI) tract for topical treatment of inflammation within the mucosal tissue. orBec(R) is being developed as a two-pill system with dual release characteristics that initially begins to release BDP in the stomach, and continues to release BDP as it travels down the GI tract for broader coverage in the intestines. orBec(R) has previously been granted Orphan Drug Designation and has received "Fast Track" designation from the FDA.

Michael Sember, Chief Executive Officer of DOR stated, "This new pivotal trial data, and collectively all the preclinical and clinical data before it, are very encouraging and clearly demonstrate to me the potential of orBec(R) in treating iGVHD. In particular, we are extremely interested in the mortality data which appears to be highly statistically significant and indicative of the drug's activity in conferring a clinical benefit to patients treated with orBec(R). In the coming weeks, we look forward to analyzing the data further and presenting it at our soon to be scheduled meeting with the FDA."

About DOR BioPharma, Inc.

DOR BioPharma, Inc. is a biopharmaceutical company focused on the development of biomedical countermeasures and therapeutic products for areas of unmet medical need. Through our BioDefense Division, we are developing biomedical countermeasures pursuant to the paradigm established by the recently enacted Project Bioshield Act of 2004. Our lead products in development are bioengineered vaccines designed to protect against the deadly effects of ricin toxin and botulinum toxin, both of which are considered serious bioterrorism threats.

Through our BioTherapeutics Division, we are developing oral therapeutic products to treat unmet medical needs. Our lead product, orBec(R) (oral beclomethasone diproprionate), is a potent, locally-acting corticosteroid being developed for the treatment of iGVHD as well as other gastrointestinal disorders characterized by severe inflammation. For further information regarding DOR BioPharma, please visit the Company's website located at

This press release contains forward-looking statements, within the meaning of Section 21E of the Securities Exchange Act of 1934, that reflect DOR BioPharma's current expectations about its future results, performance, prospects and opportunities, including statements regarding the potential use of orBec(R) for the treatment of iGVHD and the prospects for regulatory filings for orBec(R). Where possible, DOR BioPharma 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 BioPharma 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 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, that it will be able to maintain its listing on the American Stock Exchange, or that its business strategy will be successful. Important factors which may affect the future use of orBec(R) for iGVHD include the risks that: because orBec(R) did not achieve statistical significance in its primary endpoint in this 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 BioPharma expects or may never gain approval; Dor BioPharma 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). These and other factors are described from time to time in filings with the Securities and Exchange Commission, including, but not limited to, DOR BioPharma's most recent reports on Form 10-QSB and Form 10-KSB. DOR BioPharma 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.

COPYRIGHT 2004 Business Wire
COPYRIGHT 2004 Gale Group

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