Prochymal’s Development Path
In spite of its vast potential, Prochymal failed three clinical studies in 2009: a mid-stage trial in patients with chronic obstructive pulmonary disorder (COPD) and two Phase III studies in patients with steroid-resistant GvHD and acute GvHD. Phase III trials for acute and steroid-refractory GvHD are ongoing.
The company’s luck with Prochymal in GvHD changed when on February 24, Osiris reported results from its protocol 275 study of the drug as a rescue therapy among 59 children with severe, treatment-resistant GvHD. The trial was carried out under a special allowance by the FDA. Prochymal achieved an overall response rate of 63%, and among children who showed a response to therapy, survival significantly improved, according to the company.
Prochymal’s progress was stifled again, however, when an interim analysis of a Phase III trial evaluating patients with treatment-resistant Crohn disease showed that one of two dosing arms was unlikely to achieve the study endpoint of disease remission. The trial remained blinded to permit an evaluation of all 207 patients enrolled in the study. On May 5, the Phase III study was resumed based on preliminary data showing that despite initial concerns, the effect size, or difference between the Prochymal and placebo response rates, of one Prochymal dosing arm was consistent with the original statistical assumptions of the protocol and that Prochymal was significantly outperforming placebo.
The trial is evaluating Prochymal in patients with severe Crohn disease who are unresponsive to steroids, immunomodulators (azathioprine, 6-mercaptopurine, and methotrexate), and biologic agents Remicade®, Humira®, and Cimzia®. The majority of patients enrolled thus far have failed at least two immunomodulators and two biological agents.
The company does not expect to receive approval through this restarted trial. “Our goal is to use the data from this well-controlled trial to appropriately design and power an efficient pivotal program to support product approval for this devastating disease,” remarked Douglas Jacobstein, M.D., Osiris’ medical director.
If the firm can get the trial design right, it would signal good news for Osiris and development partner, Genzyme. The companies formed an alliance in 2007 for the development and commercialization of Prochymal and Chondrogen, a stem cell preparation designed for intra-articular injection. In 2007, Osiris reported results from a six-month interim evaluation of a Phase I/II trial testing Chondrogen for the regeneration of meniscus in the knee. While the company said the product met its primary safety endpoint, it did not demonstrate a statistically significant increase in the volume of meniscus as compared to placebo. Chondrogen continues to undergo testing to establish its long-term safety.