Soligenix Inc (SNGX)

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orBec(R) Clinical Summary Published in "Expert Opinion on Investigational Drugs"
Tuesday October 9, 9:03 am ET


EWING, NJ--(MARKET WIRE)--Oct 9, 2007 -- DOR BioPharma, Inc. (OTC BB:DORB.OB - News) (DOR or the Company) announced that a summary of all clinical trials to date of its drug orBec® (oral beclomethasone dipropionate, or oral BDP) in the treatment of gastrointestinal Graft-versus-Host disease (GI GVHD) has been published in the peer-reviewed medical journal Expert Opinion on Investigational Drugs. The publication "Oral Beclomethasone Dipropionate, a Topically-Active Corticosteroid for Treatment of Gastrointestinal Graft-vs.-Host-Disease Following Allogeneic Hematopoietic Cell Transplantation," is authored by George B. McDonald, MD, inventor of orBec® and Head of the Gastroenterology/Hepatology Section at the Fred Hutchinson Cancer Research Center, located in Seattle, Washington. The full article is available online at http://www.expertopin.com/doi/abs/10.1517/13543784.16.10.1709.
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Expert Opinion on Investigational Drugs is a monthly peer-reviewed journal, evaluating developments in pharmaceutical research, from animal studies to the launch of a new medicine. Authors are encouraged to express their Expert Opinion of the status of the research under review, rather than simply review the available data. The audience consists of scientists, managers and decision-makers in the pharmaceutical industry, and others closely involved in R&D. Expert Opinion on Investigational Drugs adopts a systematic approach to coverage, with each issue focusing on one of the major therapeutic areas.

The Expert Opinion paper concludes that two randomized, double-blinded placebo-controlled trials have demonstrated that orBec®, formulated as gastric-release and enteric coated pills and dosed at 8 mg/day, is safe and effective in treating acute GI GVHD when used in conjunction with a 10 day induction course of prednisone. In the pivotal Phase 3 trial, among patients eligible for prednisone taper after 10 days of induction therapy, treatment with oral BDP reduces the risk of GVHD treatment failure at study days 50 and 80 by over 60%. The type of pre-transplant conditioning and donor had no impact on the frequency of GVHD treatment failure during the 80-day study period. Both randomized trials demonstrated a 45% reduction in the risk of mortality one year after randomization, due in large part to a reduction in death due to infection and recurrent hematologic malignancy, with the greatest benefit in terms of survival among patients who had received non-myeloablative conditioning therapy and among those who received a graft from other than an HLA-matched sibling. Oral BDP is the only therapy studied in the last 30 years to effectively treat acute GVHD and reduce mortality.

Dr McDonald's opinion is that the use of orBec® in treating the pan-intestinal inflammation of acute GVHD substitutes a well characterized, topically active glucocorticoid with limited systemic bioavailability, less toxicity, and an extensive safety history, for high-dose prednisone, which is a systemic immune suppressant with a multitude of side effects, particularly a predisposition to infections, both opportunistic and routine. The same strategy has been used effectively in treating other inflammatory disorders such as acute attacks of asthma, where an induction course of prednisone to control the acute process is followed by topical, inhaled corticosteroids, including BDP.

"This is the second recent publication of our data in a well regarded peer-reviewed journal," stated Christopher J. Schaber, PhD, President and Chief Executive Officer of DOR BioPharma. "We are pleased with the exposure orBec® has been getting in the medical community as a result of these publications. Two randomized trials have shown that orBec® prevents relapses of acute GI GVHD, with an effect that has been shown to be durable even following discontinuation of therapy. We believe that orBec®, if approved, will potentially provide transplant physicians with an effective and much needed tool to treat their GI GVHD patients and improve outcomes including survival. We will continue working with the FDA and EMEA toward potential regulatory approval".

About the orBec® NDA

The data included in the NDA submission indicate that orBec® may provide clinical benefit when compared with the current standard of care, including a lowered exposure to systemic corticosteroids following allogeneic hematopoietic cell transplant. Currently there are no approved products to treat GI GVHD. Thus an approval of orBec® would represent the first directed therapy for GI GVHD.

The NDA filing is supported by data from two randomized, double-blinded, placebo-controlled clinical trials. The first trial was a 129-patient pivotal Phase 3 multi-center clinical trial of orBec® conducted at 16 leading bone marrow/stem cell transplantation centers in the US and France. The second trial was a 60-patient Phase 2 single-center clinical trial conducted at the Fred Hutchinson Cancer Research Center. Although orBec® did not achieve statistical significance in the primary endpoint of its pivotal trial, namely median time to treatment failure through Day 50 (p-value 0.1177), orBec® did achieve statistical significance in other key secondary endpoints such as the proportion of patients who were treatment failures at study days 50 and 80 and the median time to treatment failure through Day 80 (p-value 0.0226), as well as a 66% reduction in mortality among patients randomized to orBec® at 200 days post-transplant with only 5 patient (8%) deaths in the orBec® group compared to 16 patient (24%) deaths in the placebo group (p-value 0.0139). At one year post-randomization in the pivotal Phase 3 trial, 18 patients (29%) in the orBec® 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).

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. Patients who remained on orBec® until Day 50 in the pivotal study had a higher likelihood of having biochemical evidence of abnormal HPA function compared to patients on placebo.

In the Phase 2 study, the primary endpoint was the clinically relevant determination of whether GI GVHD 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® and placebo groups respectively, achieving a statistically significant p-value of 0.02. Additionally, the treatment response at Day 40 was 16 of 31 (52%) vs. 5 of 29 (17%) in the orBec® and placebo groups respectively, achieving a statistically significant p-value of 0.007.