Osiris Therapeutics (BALTIMORE, Md.), a leader in adult stem cell therapy, announced positive results from a pilot 10-patient phase II study using Prochymalâ„¢, an intravenous formulation of mesenchymal stem cells obtained from the bone marrow of healthy volunteer donors, for the treatment of patients with moderate to severe Crohn's disease (CD) who had failed to respond to standard treatments, such as steroids and infliximab (RemicadeR, Centocor, Inc). In the study, every patient evaluated reported a reduction in Crohn's Disease Activity Index (CDAI) after receiving two infusions of PROCHYMAL. There was a statistically significant decrease in mean CDAI scores of 105 points by day 28 from 341 to 236 (P = .004). There were no infusional toxicities and there were no severe adverse events attributed to Prochymal. Osiris has initiated communication with the US FDA to move forward with the design and implementation of the phase III program.

The results will be presented by Dr. Jane Onken, director of the Inflammatory Bowel Disease Clinic and associate professor of medicine at the Duke University School of Medicine in Durham, North Carolina, at the Annual Meeting of the American College of Gastroenterology on October 24. Dr. Onken was the lead investigator for the trial.

The prospective, randomized, open-label trial was conducted at four clinical sites in the US. Patients with moderate to severe CD, defined as having a CDAI of at least 220, who had previously failed treatment with steroids and other immunosuppressive agents, were given two infusions of Prochymal 7 days apart. A total of 10 patients were treated, with nine patients evaluated through the 28-day follow-up. Patients were divided into two groups and received either low-dose (2 million cells per kilogram) or high-dose (8 million cells per kilogram) Prochymal on an outpatient basis. In addition to being evaluated for safety parameters, patients were evaluated for changes in CDAI and improvement in the Inflammatory Bowel Disease Questionnaire (IBDQ). Prior to entering the trial, patients who had been treated with infliximab or other biological agents were required to complete a washout period of 90 days to preclude the possibility that response was the result of a previous treatment.

Upon entering the trial, patients' average CDAI score at baseline was 341, and they had suffered from CD for an average of 14.2 years.  Among these participants, 80% had required prior surgical intervention to treat their CD. In the course of the study, one-third of the patients had a reduction of CDAI of greater than 100 points within 14 days of treatment; each of these responders had failed previous treatment with infliximab.  Mean IBDQ scores improved significantly from baseline to day 28 (113 to 146, P = .008). One-third of the patients reported IBDQ scores of at least 170, indicating they had achieved a degree of clinical remission. Although not reaching statistical significance, there appeared to be correlation between dose and response. Patients receiving the high dose had a 72-point greater reduction in CDAI than those receiving the low-dose (CDAI reduction of 137 vs 65).

Osiris currently markets and sells Osteocel® for regenerating bone in orthopedic indications. Prochymal is in phase III clinical trials for the treatment of graft vs host disease or GVHD and is the only stem cell therapeutic currently designated by the US FDA as both an orphan drug and fast track product. 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.

—A. Techman

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