Soligenix, Inc., a late-stage biopharmaceutical company, announces the expansion and amendment of its North American licensing partnership with Sigma-Tau Pharmaceuticals, Inc. (Sigma-Tau) for the development and commercialization of orBec (oral beclomethasone dipropionate or Oral BDP) into the European territory.

As part of the amended agreement, Sigma-Tau has made a $5 million upfront payment to Soligenix.  In addition, Sigma-Tau will make additional payments to Soligenix totaling $11 million, subject to the achievement of certain milestones.  The first milestone, a $2 million payment, will be made upon the successful completion of the confirmatory Phase 3 clinical trial of orBec for the treatment of acute gastrointestinal Graft-versus-Host disease (GI GVHD). Sigma-Tau will also pay Soligenix a 40% royalty on net sales pursuant to which Soligenix will supply the drug product while maintaining worldwide manufacturing rights. All commercialization expense in the European territory, including launch activities, will be borne by Sigma-Tau.

Ugo DiFrancecso, chief executive officer of the Sigma-Tau Group which is headquartered in Rome, Italy, commented, “We are pleased to expand our partnership with Soligenix around orBec. We remain optimistic about a near-term approval in the European market and the opportunity to bring our considerable expertise in the distribution of rare disease medicines to ensure that all GI GVHD patients throughout Europe will be able to access this important medicine.”

“We expect the expanded Sigma-Tau collaboration will help us realize the full potential of orBec and oral BDP in the treatment of GI GVHD and other inflammatory GI diseases,” stated Christopher J. Schaber, PhD, president and CEO of Soligenix. “We now have an experienced commercialization partner in the second major world market and we are pleased with the robust royalty rates that we have garnered through this strong business relationship.  There will also be significant economies of scale that we will realize through having one partner in both major territories.  This partnership will provide for the launch and commercialization of orBec in North America and Europe, without any further related expense to Soligenix or its shareholders.  It also provides us with the potential for ongoing development funding across multiple indications for orBec and oral BDP.”  

orBec, oral beclomethasone dipropionate (oral BDP), is currently the subject of a confirmatory phase 3 clinical trial in the treatment of acute GI GVHD. This phase 3 trial, also referred to as the SUPPORTS protocol (Sparing Unnecessary Prednisone phase 3 orBec Randomized Treatment Study), will enrol an estimated 166 patients to confirm the clinically meaningful endpoints observed in previous phase 2 and phase 3 clinical studies. The primary endpoint is the treatment failure rate at Study Day 80. This endpoint was successfully measured as a secondary endpoint (p-value 0.005) in the company’s previous phase 3 study as a key measure of durability following a 50-day course of treatment with orBec (i.e., 30 days following cessation of treatment). The SUPPORTS trial is being conducted at major transplant centres throughout the US, Europe, and Australia and is expected to complete in the second half of 2011.  The trial is the subject of a Special Protocol Assessment (SPA) agreement that the company reached with the US Food and Drug Administration (FDA).

orBec was the subject of two prior randomized, double-blind, placebo-controlled clinical trials in acute GI GVHD. The first study was a 60-patient phase 2 single-centre clinical trial conducted at the Fred Hutchinson Cancer Research Center, which demonstrated statistical significance in its primary endpoint of controlling GI GVHD (p-value 0.02). The second study was a 129-patient pivotal phase 3 multi-centre clinical trial conducted at 16 leading bone marrow/stem cell transplant centres in the US and France. Although orBec did not achieve statistical significance in the primary endpoint of its pivotal trial, namely median 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).  At one year post-randomization in the phase 3 trial, 18 patients (29%) in the orBec group and 28 patients (42%) in the placebo group died within one year of randomization (46% reduction in mortality, p-value 0.04).

orBec represents a first-of-its-kind oral, locally acting therapy tailored to treat the GI manifestation of acute 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.  orBec is formulated for oral administration in GVHD patients 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.  Oral BDP may also have application in treating other GI disorders characterized by severe inflammation.

In addition to issued patents and pending worldwide patent applications, orBec benefits from orphan drug designations in the US and in Europe for the treatment of GI GVHD, as well as an orphan drug designation in the US for the prevention of acute GVHD and the treatment of chronic GI GVHD. Orphan drug designations provide for 7 and 10 years of market exclusivity upon approval in the US and Europe, respectively. orBec  has also received Fast Track designation from the FDA for the treatment of GI GVHD.

GVHD is a painful, debilitating and sometimes fatal disease.  It is a common disorder among immunocompromised cancer patients after receiving allogeneic stem cell or bone marrow transplants.  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 body – most frequently the gut, liver and skin.  Patients with mild-to-moderate GI GVHD typically develop symptoms of anorexia, nausea, vomiting and diarrhoea.  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.

Systemic immunosuppressive agents such as prednisone, which are the current standard treatments for GVHD, are associated with high mortality rates due to infection and debility.  Further, these drugs have not been approved for treating GVHD in the US or European Union, but rather are used off-label for this indication.

The Sigma-Tau Group is a leading international pharmaceutical group with wholly Italian-owned capital that invests in the research, development and marketing of innovative and effective treatments to improve patient well-being and quality of life.

Soligenix is a late-stage biopharmaceutical company developing products to treat life-threatening side effects of cancer treatments and serious gastrointestinal diseases, and vaccines for certain bioterrorism agents.