Osiris Therapeutics (BALTIMORE, Maryland), a leader in adult stem cell therapy, announced that Prochymalâ„¢, a preparation of mesenchymal stem cells obtained from the bone marrow of healthy adult donors and specially formulated for intravenous infusion, has received fast-track designation from the US FDA, expediting the development of the stem cell treatment for Crohn's disease that does not respond to standard therapies. Additionally, Osiris has received clearance to conduct a phase III clinical trial using Prochymal to treat this resistant form of Crohn's disease.
The phase III program for Crohn's disease will consist of two double-blind, placebo-controlled trials. As with the phase II program, the new trials will evaluate patients with Crohn's disease who are intolerant or unresponsive to standard treatments including steroids, immunosuppressants, and anti-TNF-α treatments. The primary endpoint is the induction of disease remission 28 days after treatment. Patients will have an equal chance of receiving either a high dose of Prochymal, a low dose of Prochymal, or a placebo. Initially, up to 258 subjects are scheduled to be enrolled in each trial, and those patients who respond to treatment will be eligible for re-treatment under a separate study protocol.
Osiris recently reported positive clinical trial results evaluating Prochymal for treatment-resistant Crohn's disease and graft versus host disease (GVHD), another fast-track designated indication. In a phase II study of Prochymal, for the treatment of patients with moderate-to-severe Crohn's disease who had failed to respond to standard therapies, every patient evaluated experienced a reduction in Crohn's disease activity index (CDAI). There was a statistically significant decrease in average CDAI scores of 105 points, from 341 to 236, by day 28 (P = .004). In a phase II study of Prochymal for the treatment of acute GVHD, 94% of evaluable patients responded after receiving two infusions of Prochymal. The study found that patients were twice as likely to have total clinical resolution of their disease when Prochymal was added to steroid therapy, compared to reported results for steroids alone. Osiris is currently enrolling patients in a phase III trial for treatment resistant GVHD
According to the announcement, it is believed that Prochymal alters the cytokine secretion profile of dendritic and T-cell subsets, thereby resulting in a shift from a proinflammatory to an anti-inflammatory state and arresting disease progression. Laboratory data indicate that the stem cells in Prochymal are able to down-regulate the production of proinflammatory cytokines, including TNF-α and interferon-gamma, and respond according to the level of inflammation present. It is hoped that this proportional response will lead to a treatment that avoids many of the dangerous side effects associated with systemic immunosuppressive therapy and provide a safer alternative for treating patients with serious inflammatory diseases. Furthermore, it is believed that Prochymal facilitates the repair of previously damaged tissue through the secretion of growth factors that promote tissue regeneration and block apoptosis.
The FDA established the fast track designation to facilitate the development and accelerate the pre-market review of treatments for serious and life-threatening conditions, so that these products can reach approval more rapidly. To receive fast track designation, the product must address a serious unmet medical condition, and be supported by strong results from preclinical or clinical testing demonstrating the product potential.
Prochymal is the only stem cell therapeutic currently designated by the US FDA as both an orphan drug and a fast track product (for GVHD). If approved, prochymal would likely be the first pure stem cell therapy to be marketed. The company's pipeline of internally developed biologic drug candidates under evaluation also includes Chondrogenâ„¢ for regenerating cartilage in the knee. Osiris currently markets and sells Osteocel® for regenerating bone in orthopaedic indications. For the third quarter, ending September 30, 2006, sales of Osteocel grew 50%, as compared to the second quarter, to $2.5 million.
—A. Techman
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