Oral beclomethasone dipropionate: a topically active corticosteroid for the treatment of gastrointestinal graft-versus-host disease following allogeneic hematopoietic cell transplantation

Abstract

Beclomethasone dipropionate (BDP) is a topically active anti-inflammatory corticosteroid. Oral BDP is metabolized in the intestine to a potent metabolite, 17-beclomethasone monopropionate (17-BMP). An oral formulation (orBec^®; DOR BioPharma), consisting of a gastric release and an enteric-coated pill, was studied in patients with acute gastrointestinal graft-versus-host disease, an inflammatory disorder that is common after allogeneic hematopoietic cell transplantation. Randomized trials demonstrated that orBec is safe and effective in treating acute gastrointestinal graft-versus-host disease (GVHD) when used with a short induction course of prednisone, reducing the risk of GVHD treatment failure by > 60% and reducing mortality 1 year after randomization by 45%, with fewer deaths due to infection and recurrent malignancy. The type of conditioning and the type of donor had no effect on the frequency of GVHD treatment failure during the 80-day study period; the greatest benefit in terms of survival was among patients who had received reduced-intensity conditioning therapy and among those who received a graft from other than a human leukocyte antigen-matched sibling. orBec controls the intestinal inflammatory process of GVHD and avoids prolonged exposure to prednisone, which is the present standard of care. Oral BDP is the only therapy to be studied in the last 30 years to effectively treat acute GVHD and reduce mortality.

Keywords::

• allogeneic hematopoietic cell transplant
• anti-inflammatory agent
• beclomethasone dipropionate
• graft-versus-host disease
• oral BDP
• orBec^®
• safety
• survival
• transplant outcomes

Disclosure

The pivotal Phase III trial for treatment of gastrointestinal GVHD was sponsored by Enteron Pharmaceuticals (a wholly owned subsidiary of DOR BioPharma, Inc., Florida, USA). G McDonald is a consultant to DOR BioPharma, Inc. and has an equity position with the company.

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