Soligenix, Inc., a clinical stage biopharmaceutical company, has initiated a phase 2, randomized, double-blind, placebo-controlled study evaluating orBec (oral beclomethasone 17,21-dipropionate or BDP) as a treatment for the gastrointestinal (GI) manifestations of chronic Graft-versus-Host disease (GVHD). The study is partially funded by the National Cancer Institute (NCI) which has awarded Soligenix a Small Business Innovation Research (SBIR) grant to support the conduct of a phase 2 clinical trial. The award provides Soligenix with approximately $300,000 over a two-year period.
The phase 2 study is designed as a multicenter, pilot study enrolling patients that have received allogeneic haematopoietic cell transplantation (HCT) at least 100 days earlier, have documented chronic GVHD in at least one organ outside the GI tract, and have a mucosal biopsy consistent with GI GVHD. The primary efficacy objective of the study is to estimate the proportion of subjects with chronic GVHD with GI involvement who achieve a complete response, partial response or minimal response of GI GVHD signs and symptoms when treated with orBec for up to 16 weeks. Response will be assessed using a composite score based on the symptoms of satiety, nausea/vomiting, and anorexia.
“Survival of patients undergoing allogeneic HCT has markedly improved over the last decade, leading to a growing number of long-term survivors with chronic GVHD. In these patients, gastrointestinal GVHD can be a persistent problem whether layered on top of extraintestinal chronic GVHD or dominating the clinical picture”, stated George B McDonald, MD, Member, Fred Hutchinson Cancer Research Center and Professor of Medicine at the University of Washington. “Based on the pharmacology of orally-delivered BDP, which delivers a potent glucocorticoid directly to the GI mucosa, orBec offers a promising option to address disabling GI symptoms in patients with chronic GVHD.”
“We are pleased by the continued support of NCI as a collaborator supporting our oncology focused BDP clinical programmes,” stated Christopher J Schaber, president and chief executive officer of Soligenix. “We look forward to working with our clinical centres to complete this study as soon as possible to continue development of orBec with the aim of addressing this orphan disease.”
Graft-versus-Host disease (GVHD) is a major complication of allogeneic haematopoietic cell transplantation. GVHD is an inflammatory disease initiated by T cells in the donor graft that recognize histocompatibility and other tissue antigens of the host, and is mediated by a variety of effector cells and inflammatory cytokines. GVHD presents in both acute and chronic forms, and each is commonly associated with inflammation of gastrointestinal mucosa along with symptoms of anorexia, nausea, vomiting, and diarrhoea. The symptoms of chronic GVHD typically present at between 100 days and three years post-transplant.
Chronic GVHD has features resembling autoimmune and other immunologic disorders such as scleroderma, Sjögren syndrome, primary biliary cirrhosis, wasting syndrome, bronchiolitis obliterans, immune cytopenias and chronic immunodeficiency. The manifestations of chronic GVHD may be restricted to a single organ or tissue or may be widespread. Chronic GVHD can lead to debilitating consequences, e.g., joint contractures, loss of sight, end-stage lung disease, or mortality resulting from profound chronic immune suppression leading to recurrent or life-threatening infections. Gastrointestinal (GI) GVHD in patients with chronic GVHD can lead to persistent symptoms, weight loss, and malabsorption of nutrients.
Treatment of chronic GVHD is a challenge because it can be refractory to frontline immunosuppression. High-dose systemic corticosteroids are used with some success but carry significant toxicity. The risks of prolonged immunosuppression include local and disseminated infections, Epstein-Barr virus associated lymphoproliferative disease, hypothalamic-pituitary-adrenal (HPA) axis suppression, myopathy, glucose intolerance, neuropsychiatric disease and bone demineralization. One of the goals of therapy of chronic GVHD is to minimize systemic immune suppression by treating involved organs with topical therapy whenever possible.
It is estimated, based upon review of historic published studies and reports and an interpolation of data on the incidence of chronic GVHD, that there are 6,000 patients annually in the US, with a comparable number in Europe that suffer from chronic GVHD.
orBec represents a first-of-its-kind oral, locally acting therapy tailored to treat the GI manifestation of chronic GVHD, the organ system where GVHD is most frequently encountered and highly problematic. orBec is intended to reduce the need for systemic immunosuppressive drugs such as prednisone to treat chronic GI GVHD. The active ingredient in orBec is beclomethasone dipropionate (BDP), 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 specifically formulated for oral administration as a single product consisting of two tablets, one immediate release tablet providing BDP to the upper sections of the GI tract and one delayed release tablet providing BDP to the lower sections of the GI tract.
In addition to issued patents and pending worldwide patent applications held by or exclusively licensed to Soligenix, orBec has received orphan drug designation in the US for the treatment of chronic GI GVHD. Orphan drug designations provide for 7 years of market exclusivity upon approval in the US.
Soligenix is a clinical stage biopharmaceutical company developing products to treat serious inflammatory diseases where there remains an unmet medical need, as well as developing several biodefense vaccines and therapeutics.