Osiris Therapeutics, Inc. announced preliminary results for two phase III trials evaluating Prochymal for the treatment of acute graft versus host disease (GvHD). GvHD, the most common complication of bone marrow transplantation, is a life-threatening disease for which there is currently no approved treatment. Prochymal showed significant improvements in response rates in difficult-to-treat liver and gastrointestinal GvHD, however neither trial reached its primary endpoint.

Key findings from the GvHD trials include: There was no statistical difference between Prochymal and placebo on the primary endpoints for either the steroid-refractory (35% vs. 30%, n=260) or the first-line (45% vs. 46%, n=192) GvHD trials; The primary endpoint for the steroid-refractory GvHD trial (durable complete response) for the perprotocol population approached statistical significance (40% vs. 28%, p=0.087, n=179); In patients with steroid-refractory liver GvHD, treatment with Prochymal significantly improved response (76% vs. 47%, p=0.026, n=61) and durable complete response (29% vs. 5%, p=0.046); Prochymal significantly improved response rates in patients with steroid-refractory gastrointestinal GvHD (88% vs. 64%, p=0.018, n=71); In paediatric patients, Prochymal showed a strong trend of improvement in response rates (86% vs. 57%, p=0.094, n=28).

"These data are still preliminary and further analysis is needed to gain a full appreciation of the results of these rigorous, double-blind, placebo-controlled trials," said C. Randal Mills, Ph.D., president and chief executive officer of Osiris Therapeutics. "We are encouraged to see Prochymal significantly improve response rates above standard of care in GvHD patients who currently have no good treatment options. We will meet with the FDA as soon as possible to discuss the most appropriate and efficient path forward for Prochymal in this life-threatening indication. "

Protocol 265 was designed to evaluate Prochymal as a first-line agent for the treatment of acute GvHD in combination with steroid therapy. The majority of patients in this trial were suffering from skin GvHD, which responded significantly better to steroids than had been previously reported in controlled trials. This high response rate to standard of care diminished the potential for Prochymal to demonstrate an effect.

In the more severe, steroid-refractory GvHD setting (protocol 280), the benefit of adding Prochymal to second-line therapy was evaluated. Prochymal approached statistical significance for the primary endpoint in the per-protocol patient population which is the group of patients that met all of the study protocol requirements, such as inclusion and exclusion criteria. Additionally, Prochymal significantly improved response rates to liver and gastrointestinal GvHD, for which there is currently no known reliable therapy.

Notably, the Prochymal cohort had more severe GvHD (27% of Prochymal patients had grade D GvHD, the most severe form, vs. 16% of placebo patients, p=0.05).

Based upon the results of the steroid-refractory GvHD trial, Osiris plans to file an amendment with the FDA to the current expanded access program, broadening the entry criteria to include patients with severe GvHD of the liver.

The phase III trial evaluated the safety and efficacy of Prochymal in conjunction with standard of care for treatment of patients who had failed to respond to corticosteroid treatment for acute GvHD. The clinical trial is a double-blind, placebo-controlled study. Patients were randomized to either Prochymal or placebo at a 2:1 ratio. GvHD assessments performed according to the International Bone Marrow Transplant Registry (IBMTR) were used in the trial to detect improvements in subjects treated with Prochymal. The primary endpoint for this trial is durable complete response defined as complete resolution of GvHD for a duration of at least 28 days. The trial enrolled 260 patients from 72 leading bone-marrow transplant centres across the United States, Canada, Europe and Australia.

The phase III double-blind, placebo controlled trial evaluated the safety and efficacy of Prochymal in conjunction with steroid therapy in patients with newly diagnosed acute GvHD, grades B-D. The primary endpoint of the trial is the proportion of patients surviving at least 90 days that achieve a complete response when Prochymal is added to steroid therapy as compared to those receiving steroids alone. Patients are considered treatment failures if they do not achieve a complete response within 28 days of initiating treatment, if the steroid dose is increased or other immunosuppressive agents are added, or if the patient does not survive 90 days following initial treatment. The trial enrolled 192 patients from 52 leading transplant centres across the United States, Canada and Australia.

GvHD represents a major unmet medical need with no approved treatment. It is the most common complication of allogeneic (using cells from a family member, unrelated donor or cord blood unit) haematopoietic stem cell transplantation (HSCT). GvHD occurs when immune cells from the donated cell population (the graft) attack the transplanted patient's body cells (the host) because the recipient cells are seen as "foreign." Organs that are mainly affected by the immunological attack are the gastrointestinal tract, skin, and liver.

Acute GvHD is a potentially life-threatening complication that arises in approximately 50% of all patients who receive an allogeneic HSCT. Severe acute steroid-refractory GvHD is fatal in up to 90 percent of cases. Current treatments are marginally effective with significant side effects.

Prochymal is a preparation of mesenchymal stem cells (MSCs) formulated for intravenous infusion. The MSCs utilized in Prochymal are isolated from the bone marrow of healthy young adult donors, avoiding the controversy surrounding embryonic and fetal cell sources. They are grown in culture, permitting large-scale production. Because the cells can be expanded, thousands of doses can be produced from a single donation.

Studies suggest MSCs are able to safely facilitate tissue repair through a number of mechanisms. Specifically, these studies have indicated that MSCs are able to down-regulate severe inflammation and work at the cellular level to rebuild damaged tissue through the coordinated release of tissue specific growth factors.

Prochymal is being evaluated in three, double-blind, placebo-controlled Phase III studies, including steroidrefractory GvHD, acute GvHD and Crohn's disease. Prochymal has been granted Fast Track status by the FDA for GvHD and Crohn's disease, and is the first stem cell product to receive FDA expanded access approval, making the product available now to children with life-threatening GvHD. Prochymal also obtained Orphan Drug status by FDA and the European Medicines Agency for GvHD. Prochymal is also being studied in phase II trials for the treatment of acute myocardial infarction, COPD and type 1 diabetes.

Osiris Therapeutics, Inc. is the leading stem cell therapeutic company focused on developing products to treat serious medical conditions in the inflammatory, orthopaedic and cardiovascular areas.