ODAC: orBec Yields No `Substantial Efficacy` in GI GVHD

ODAC: orBec Yields No 'Substantial Efficacy' in GI GVHD
Published on Cancer Network (http://www.cancernetwork.com)
ODAC: orBec Yields No 'Substantial Efficacy' in GI GVHD
June 01, 2007 | Gastrointestinal Cancer [1]
The FDA's Oncologic Drugs Advisory Committee (ODAC) voted 7-to-2 that the data presented by
DOR BioPharma in support of its new drug application for orBec (beclomethasone dipropionate)
failed to demonstrate substantial efficacy for orBec for its intended purpose
SILVER SPRING, Maryland—The FDA's Oncologic Drugs Advisory Committee (ODAC) voted 7-to-2 that
the data presented by DOR BioPharma in support of its new drug application for orBec
(beclomethasone dipropionate) failed to demonstrate substantial efficacy for orBec for its intended
purpose, a conclusion also reached by the FDA's review team. The company is seeking approval for
orBec for the treatment of graft-vs-host disease (GVHD) involving the gastrointestinal tract in
conjunction with an induction course of high-dose prednisone or prednisolone. The oral drug is a
diester of beclomethasone, a synthetic corticosteroid with anti-inflammatory and
immunosuppressive effects. It was granted orphan drug designation and fast track status during its
development.
The company submitted findings from two trials of orBec as a treatment for GVHD following
allogeneic hematopoietic cell transplantation to support the drug's efficacy. The pivotal study, a
phase III, multicenter, randomized, double-blind, placebo-controlled trial, involved 129 patients with
grade 2 GVHD who received a 10-day induction course of high-dose prednisone and either orBec or
placebo for 50 days. The supportive study was a single-institution, randomized, double-blind,
placebo-controlled phase II trial in 60 patients with GI GVHD.
The pivotal study's primary endpoint (time to GVHD treatment failure through study day 50) failed to
reach significance (P = .118) despite a 37% lower risk of treatment failure for the orBec group.
Through day 80 (a secondary endpoint), the difference was significant (P = .023) with a 46% lower
risk of treatment failure for the orBec patients.
A secondary efficacy endpoint (proportion of patients with GVHD treatment failure by study day 50)
showed a significant difference in favor of orBec (31% vs 48% for placebo, P = .05). By day 80, the
difference was 39% vs 65% (P = .003).
At day 200 post-transplant (a safety endpoint), orBec patients had a higher survival rate (92% vs
76% for placebo patients) (HR 0.29, P = .014). The estimated 1-year post-randomization mortality
was significant in favor of orBec (29% vs 42% for placebo) (HR 0.54, P = .04). This was not a
pre-specified endpoint. "Patients with GVHD randomized to orBec had meaningful reductions in
mortality," said George B. McDonald, MD, head of gastroenterology/hematology, Fred Hutchinson
Cancer Research Center.
In its analysis, FDA emphasized that the pivotal study had failed its primary efficacy endpoint and
that the trial had a major imbalance in the number of nonmyeloablative transplants between the
treatment and placebo arms. "Once the study failed on the primary endpoint, any further analyses
are exploratory, and statistical significance cannot be determined," said FDA medical reviewer Nancy
S. Scher, MD.
Source URL:
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Links:
[1] http://www.cancernetwork.com/gastrointestinal-cancer
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