Soligenix Announces Preliminary Results of its Phase 2 Clinical Trial of orBec® in the Prevention of Acute GVHD

PRINCETON, N.J., Oct. 25 /PRNewswire-FirstCall/ -- Soligenix, Inc. (Soligenix or the Company) (OTC Bulletin Board: SNGX), a late-stage biopharmaceutical company, today reported preliminary results from its Phase 2 "proof-of-concept" exploratory clinical trial of orBec® for the prevention of acute Graft-versus-Host disease (GVHD) in patients undergoing myeloablative conditioning regimens with initiation of dosing prior to hematopoietic cell transplantation (HCT) and continuing through the post-transplantation period.  The preliminary results indicate that orBec® appears safe and well tolerated in this patient population, but did not achieve statistical significance in the primary endpoint, which was the proportion of subjects who developed acute GVHD with severity sufficient to require systemic immunosuppressive treatment on or before day 90 after transplantation.  However, an encouraging result was that use of orBec® resulted in fewer cases of more severe acute GVHD grades IIb-IV (21% vs. 33% of patients receiving placebo), although this difference was not statistically significant.  This result has the potential to be clinically relevant because GVHD grades IIb-IV are associated with more severe disease involving the skin and liver as well as being associated with poorer outcomes, including mortality rates that approach 100% in the grade IV patient population.  Further analysis of the complete dataset continues and is aimed at identifying other potential effects seen with orBec® in preventing acute GVHD.

The Phase 2 prevention study was a randomized, double-blind, placebo-controlled trial that enrolled 140 patients who had been randomized to either orBec® or placebo at a 2:1 ratio.  Prior to HCT, patients began study drug at the start of their conditioning regimen and continued through day 75 following HCT. The study was conducted primarily at the Fred Hutchinson Cancer Research Center in Seattle, WA and was supported, in large part, by a National Institutes of Health (NIH) grant.  The impetus for this NIH-funded prevention study came from two double-blind, randomized, placebo-controlled trials showing that orBec® was effective and safe as a treatment for acute gastrointestinal (GI) GVHD.  

Paul J. Martin, MD, Principal Investigator for the Phase 2 study and a Member, Fred Hutchinson Cancer Research Center stated, "Trials with orBec® have shown a consistent and positive clinical response in the treatment of acute GI GVHD.  We therefore designed a trial to determine whether orBec® could be used to prevent GVHD. Preliminary analysis indicates that administration of orBec®  starting before transplantation did not provide a statistically significant clinical advantage in preventing acute GVHD in this study, possibly because of confounding factors associated with the chemotherapy or radiation.  Preventive administration of orBec® to reduce the incidence or severity of GVHD warrants further investigation, for example, by starting orBec® dosing after transplantation, closer to the initial inflammatory insult of acute GVHD.  We are continuing to analyze the data in order to gain a better understanding of potential preventive treatment effects in this patient population and to determine the best approach for subsequent study."   

Dr. Martin continued, "In my mind, the results from this prevention study have no clinical implication regarding the likelihood of success in the ongoing Phase 3 study of orBec® for the treatment of acute GI GVHD."

"This Phase 2 clinical trial was truly proof-of-concept and the first of its kind. It was an aggressive approach to determining if a topically-active steroid therapy, like orBec®, could have an impact on preventing the development of GVHD very early in the disease process," added Brian L. Hamilton, MD, PhD, Chief Medical Officer of Soligenix.  "The trend towards less severe acute GVHD in the patients treated with orBec® is encouraging. We are continuing to analyze the Phase 2 data for other clinically meaningful signals."

Dr. Hamilton continued, "We obviously remain confident in the ultimate success of our confirmatory Phase 3 study of orBec® in the treatment of acute GI GVHD. This Phase 3 trial is anchored by more than 15 years of clinical research in the treatment setting, including positive results from two prior randomized, double-blind, placebo-controlled studies.  The current Phase 3 study is designed to replicate the endpoint of treatment failure rate at Study Day 80, which was successfully measured as a secondary endpoint (p-value 0.005) in the Company's previous Phase 3 study.  Accordingly, there is no correlation between the prospects for success in these distinctly different therapeutic indications and patient populations.  We continue to make good progress towards completing the confirmatory Phase 3 trial in treatment of acute GI GVHD in the second half of next year."

About orBec®

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 enroll 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 centers 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-center 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-center clinical trial conducted at 16 leading bone marrow/stem cell transplant centers 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.

About GVHD

GVHD is a debilitating and painful 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 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.

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.

About Soligenix, Inc.

Soligenix, Inc. (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. Soligenix's lead product, orBec® (oral beclomethasone dipropionate or BDP), is a potent, locally acting corticosteroid being developed for the treatment of acute gastrointestinal Graft-versus-Host disease (GI GVHD), a common and potentially life-threatening complication of hematopoietic cell transplantation. orBec® is currently the subject of a $1.2M FDA Orphan Products Grant to support the confirmatory Phase 3 clinical trial for the treatment of acute GI GVHD. Soligenix is also conducting an NIH-supported Phase 1/2 clinical trial of SGX201 in the prevention of acute radiation enteritis.  Additionally, Soligenix has a Lipid Polymer Micelle (LPM™) drug delivery technology for the oral delivery of leuprolide for the treatment of prostate cancer and endometriosis.

Through its Biodefense Division, Soligenix is developing biomedical countermeasures pursuant to the Project BioShield Act of 2004. Soligenix's lead biodefense product in development is a recombinant subunit vaccine called RiVax™, which is designed to protect against the lethal effects of exposure to ricin toxin. RiVax™ has been shown to be well tolerated and immunogenic in a Phase 1 clinical trial in normal volunteers. RiVax™ is also the subject of a $9.4 million NIH grant received by the Company supporting development of new heat stable vaccines.

For further information regarding Soligenix, Inc., please visit the Company's website at www.soligenix.com.

This press release contains forward-looking statements that reflect Soligenix, Inc.'s current expectations about its future results, performance, prospects and opportunities. Statements that are not historical facts, such as "anticipates," "believes," "intends," or similar expressions, are forward-looking statements. These statements are subject to a number of risks, uncertainties and other factors that could cause actual events or results in future periods to differ materially from what is expressed in, or implied by, these statements. Soligenix cannot assure you that it will be able to successfully develop or commercialize products based on its technology, including orBec®, SGX201, RiVax™, and LPM™, particularly in light of the significant uncertainty inherent in developing vaccines against bioterror threats, manufacturing and conducting preclinical and clinical trials of vaccines, and obtaining regulatory approvals, that its cash expenditures will not exceed projected levels, that product development and commercialization efforts will not be reduced or discontinued due to difficulties or delays in clinical trials or due to lack of progress or positive results from research and development efforts, that it will be able to successfully obtain any further grants and awards, maintain its existing grants which are subject to performance, enter into any biodefense procurement contracts with the US Government or other countries, that the US Congress may not pass any legislation that would provide additional funding for the Project BioShield program, that it will be able to patent, register or protect its technology from challenge and products from competition or maintain or expand its license agreements with its current licensors, or that its business strategy will be successful. Important factors which may affect the future use of orBec® for gastrointestinal GVHD include the risks that: the FDA's requirement that Soligenix conduct additional clinical trials to demonstrate the safety and efficacy of orBec® will take a significant amount of time and money to complete and positive results leading to regulatory approval cannot be assumed; Soligenix is dependent on the expertise, effort, priorities and contractual obligations of third parties in the clinical trials, manufacturing, marketing, sales and distribution of its products; orBec® may not gain market acceptance if it is eventually approved by the FDA; and others may develop technologies or products superior to orBec®. Factors affecting the development and use of SGX201 and LPM™ are similar to those affecting orBec®. These and other factors are described from time to time in filings with the Securities and Exchange Commission, including, but not limited to, Soligenix's reports on Forms 10-Q and 10-K. Unless required by law, Soligenix assumes no obligation to update or revise any forward-looking statements as a result of new information or future events.

SOURCE Soligenix, Inc.