Washington Editor

On the success of a Phase II trial, Osiris Therapeutics Inc. is moving forward with a Phase III pivotal trial of its mesenchymal stem cell therapy Prochymal as a first-line agent to treat acute graft-vs.-host disease (GVHD).

GVHD is a life-threatening complication of allogeneic bone-marrow transplantation in which functional immune cells in the transplanted marrow recognize the recipient as foreign and mount an immunologic attack.

The disease occurs in up to 50 percent of bone-marrow transplant patients and affects the digestive system, skin, liver and other body systems.

There currently is no approved treatment on the market for GVHD. However, patients with the condition generally are treated with steroids.

Osiris' Phase III double-blind, placebo-controlled trial will evaluate the safety and efficacy of Prochymal in combination with steroid therapy in treating 180 patients with newly diagnosed acute GVHD grades II-IV, said Osiris CEO Randal Mills.

The primary endpoint of the trial is the proportion of patients who achieve a complete response and are alive at day 90 when Prochymal is added to standard steroid therapy compared with steroid therapy alone.

Patients will be 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 the 90-day evaluation period.

Results of the Phase II randomized prospective, open-label trial showed that 77 percent of patients treated with Prochymal experienced complete remission of GVHD within 28 days, Mills told BioWorld Today.

At six months, 61 percent of patients who received the product had a durable response requiring no additional immunosuppressive therapy, clinical intervention or increased steroid use, he said.

In the Phase II trial, patients were given standard steroids and two infusions of Prochymal 72 hours apart at the onset of moderate to severe GVHD, Mills explained.

Of the 32 study participants, 24 achieved a complete response rate, five patients had a partial response and two patients did not respond, he said, noting that one patient dropped out of the study.

In the Phase III trial of Prochymal in acute GVHD, Mills said, 180 patients at more than 40 sites will be administered doses of the stem cell agent twice a week for three weeks in combination with standard steroids.

In a separate Phase III study that got under way last year, Prochymal is being studied in 240 patients with steroid-refractory GVHD, a more severe and deadly condition, Mills said.

Once GVHD patients become steroid-refractory, he said, "it's an immediately life-threatening disease. . . . They are very sick at that point, and because they are so sick and have deteriorated so much, their prognosis is not good," Mills said.

Prochymal use in patients with steroid-refractory GVHD, he said, generally is considered a "rescue-scenario" therapy. But if therapy with Prochymal is provided earlier in patients with GVHD as a first-line treatment before the disease progresses, a patient's prognosis is much better, Mills said.

He noted that the Phase III study for the steroid-refractory GVHD indication is being conducted in 70 centers in the U.S., Canada, Australia and Europe. "It's a global effort, and if we are successful, we will have a product which can help alleviate GVHD literally across the globe. It's certainly a worthwhile cause," Mills declared.

Columbia, Md.-based Osiris plans to first submit a biologics license application (BLA) for the steroid-refractory GVHD indication, Mills said, noting that results from the Phase III study for that indication could be available by mid-2008.

After Phase III study results are available for the acute GVHD indication, he added, Osiris will submit a supplement to its BLA application.

The firm also is studying Prochymal, which has been granted fast-track and orphan drug status by the FDA, as a preventive agent for myocardial infarction and as a treatment for Crohn's disease.

In addition, Mills said, Osiris has partnered with Cambridge, Mass.-based Genzyme Corp. to develop Prochymal to treat acute radiation syndrome.

The two firms are hoping that the military and the Department of Health and Human Services will recognize the therapy as a medical countermeasure to nuclear terrorism and other radiological emergencies.

The anti-inflammatory properties and tissue regeneration capabilities of adult stem cells may allow effective treatment of the multicomponent syndromes cause by high levels of radiation exposure, according to Osiris.

Tests of Prochymal have shown that the product currently has at least a two-year shelf life, Mills said, and therefore, the product could be stored in HHS's Strategic National Stockpile - a national cache of anti-infectives, chemical antidotes, vaccines, and medical supplies that can be deployed anywhere in the U.S. or its territories within 12 hours of an event.

Osiris' pipeline of internally developed biologic drug candidates also includes Chondrogen for arthritis in the knee, and Provacel for repairing heart tissue following a heart attack.

Shares of Osiris (NASDAQ:OSIR) dropped 6 cents Wednesday to close at $14.25.