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Phase 3 Trial of Oral Beclomethasone Dipropionate Completed
The news arrives on the heels of Monday's announcement of a $5.2 million challenge grant award given to DOR from the National Institutes of Allergy and Infectious Diseases (NIAID) for further development of the Company's ricin vaccine (see DOR media release dated September 13, 2004).
Mr. Green put the week's new events into perspective during his presentation: "The completion of the pivotal phase III clinical trial is a substantial milestone that allows us to move forward in the drug approval process, pending positive results. Further, the funding from the NIH is validation for our biodefense program giving DOR one late stage therapeutic (orBec®), and two biodefense products (Rivax(TM) and BT-Vacc(TM)) with the potential to move more quickly through the clinical development stages."
OrBec®, 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, locally-active glucocorticoid that has a topical effect on inflamed tissue that is estimated to be 500-5,000 times more active than dexamethasone and hydrocortisone. BDP has been marketed in the U.S. and worldwide since the early 1970s as a nasal spray, a metered dose inhaler and a cream for the treatment of patients with allergic rhinitis, asthma and skin rash, respectively. DOR's oral formulation of BDP is delivered to the gastrointestinal (GI) tract for topical treatment of inflammation within the mucosal layer. OrBec® 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.
The initial indication that orBec® is being developed for is the treatment of intestinal Graft-versus-Host Disease (GvHD), a severe, potentially life-threatening complication of allogeneic bone marrow and stem cell transplants. The product has previously received Orphan Drug designation and fast track designation by the U.S. Food and Drug Administration.
"As previously stated, we expect to announce top line data from this trial in the fourth quarter of 2004, and, pending results, anticipate filing a New Drug Application for marketing authorization possibly as early as first quarter 2005," said Mr. Green.
About the Phase III Pivotal Trial
One hundred and twenty-nine (129) patients were enrolled in the 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 treated in the Phase III clinical trial were treated initially with a constant daily dose of prednisone or equivalent systemic corticosteroid, in combination with either orBec® or placebo for the first 10 days. On day 10, if patients were responding to treatment, the prednisone was rapidly tapered and the orBec® or placebo continued. The primary endpoint of the study is a comparison of the two treatment arms of the median time to treatment failure, defined as the need for additional therapies due to uncontrolled signs or symptoms of GvHD. Other endpoints in the study include a comparison of the proportion of treatment failures at specified time points, as well as a comparison of cumulative exposure to systemic steroids.
Oral BDP was previously tested in a randomized, placebo-controlled Phase II study (Gastroenterology, 1998; 115: 28-35). In that study, 60 patients with intestinal GvHD were randomized to receive conventional therapy plus either oral BDP or placebo. Initial responders continued to take BDP or placebo for an additional 20 days, during which the conventional therapy was rapidly tapered. The treatment response at day 30 was 22 of 31 (71%) vs. 12 of 29 (41%) in the placebo group, respectively (P= 0.02).
Source: DOR BioPharma, Inc.