orBec® GVHD Treatment
Soligenix's lead product orBec® represents a first-of-its-kind oral, locally acting therapy tailored to treat the gastrointestinal (GI) manifestation of Graft-versus-Host disease (GVHD), the organ system where GVHD is most frequently encountered and highly problematic. orBec® is intended to reduce the need for systemic immunosuppressive drugs to treat GI GVHD. Beclomethasone dipropionate (BDP), the active ingredient in orBec®, is a highly potent, topically active corticosteroid that has a local effect on inflamed tissue. BDP has been marketed in the US and worldwide since the early 1970s 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. orBec® 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 distal portions of the GI tract.
Acute GI GVHD is a debilitating and painful disease and constitutes an unmet medical need. It is a common disorder among immunocompromised cancer patients after receiving hematopoietic cell transplantation. 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 (host's) body - most frequently the gastrointestinal tract, liver and skin. Patients with mild-to-moderate GI GVHD typically develop symptoms of anorexia, nausea, vomiting and diarrhea. 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.
Soligenix has initiated a confirmatory, pivotal, Phase 3 clinical trial evaluating its lead product orBec® for the treatment of acute GI GVHD under agreements with both the FDA and EMEA. The agreement with the FDA was gained via the FDA's Special Protocol Assessment (SPA) procedure. An agreement via the SPA procedure is an agreement with the FDA that a Phase 3 clinical trial design (e.g., endpoints, sample size, control group and statistical analyses) is acceptable to support a regulatory submission seeking new drug approval. The agreement with the EMEA was obtained via the procedure for requesting Protocol Assistance. Based on data from the prior Phase 3 study of orBec®, the confirmatory, Phase 3 clinical trial is a highly powered, double-blind, randomized, placebo-controlled, multi-center trial and will seek to enroll an estimated 166 patients. The primary endpoint on the new study is the treatment failure rate at Study Day 80. This endpoint was successfully measured as a secondary endpoint (p-value 0.005) in the previous Phase 3 study which enrolled 129 patients. This clinical trial is currently enrolling and is targeted to complete in the first half of 2011.
Two prior randomized, double-blind, placebo-controlled Phase 2 and 3 clinical trials support orBec®'s ability to provide clinically meaningful outcomes when compared with the current standard of care, including a lowered exposure to systemic corticosteroids following allogeneic transplantation. Currently, there are no approved products to treat GI GVHD. The first trial was a 60-patient, Phase 2, single-center clinical trial conducted at the Fred Hutchinson Cancer Research Center. The second trial was a 129-patient, Phase 3, multi-center clinical trial of orBec® conducted at 16 leading hematopoietic cell transplantation centers in the US and France. Although orBec® did not achieve statistical significance in the primary endpoint, namely 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 free of GVHD at Day 50 (p-value 0.05) and Day 80 (p-value 0.005) 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).
In the Phase 2 study, the primary endpoint was the clinical investigator's determination of acute GI GVHD treatment failure at Study Day 30 (the end of treatment). This determination was in large part made by whether or not they were able to consume at least 70% of their estimated caloric requirement. The GVHD treatment response at Day 30 was 22 of 31 (71%) vs. 12 of 29 (41%) in the orBec® and placebo groups, respectively (p-value 0.02). Additionally, the GVHD treatment response at Day 40 (10 days post-cessation of therapy) was 16 of 31 (52%) vs. 5 of 29 (17%) in the orBec® and placebo groups, respectively (p-value 0.007).
