Perceived trial design flaw not sufficient to mask promising results.

Osiris Therapeutics has restarted patient enrollment into a Phase III trial (Protocol 603) evaluating its stem cell therapy, Prochymal, in patients with treatment-resistant Crohn disease. The trial was stopped in March 2009 due to concerns that a flaw in its design would make it difficult to detect a treatment effect due to higher than expected placebo-response rates.

An interim analysis of existing data from the study has now shown that for the primary endpoint of disease remission, Prochymal therapy approached statistical significance in the intent-to-treat population and reached significance in the per-protocol population.

Restart of the trial follows a discussion with FDA about the interim analysis data, and patient enrollment will continue for the best-performing Prochymal dose arm and placebo arm. A second linked study, Protocol 610, had been evaluating the use of Prochymal to maintain response in patients who had failed all other available treatments. This trial has been discontinued to remove the potential for bias, Osiris notes.

“We will have a better understanding of the benefits Prochymal may offer to patients with treatment-resistant Crohn  disease after enrollment has been completed and the full dataset has been thoroughly analyzed,” commented Douglas Jacobstein, M.D., director of the Crohn program at Osiris. “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.”

Prochymal is an intravenously administered formulation of mesenchymal stem cells derived from healthy adult bone marrow. The product is being evaluated in Phase III trials for acute and steroid-refractory graft versus host disease (GvHD) as well as Crohn disease. It has been granted fast-track status by FDA for the GvHD and Crohn disease indication, and is also available under the agency’s expanded access program to patients with life-threatening GvHD.

Prochymal is also being evaluated in Phase II trials for the repair of heart tissue following a heart attack, the protection of pancreatic islet cells in patients with type 1 diabetes, and the repair of lung tissue in patients with chronic obstructive pulmonary disease.

Osiris and Genzyme inked their deal for development of Prochymal as well as Osiris’ stem cell-based arthritis therapy, Chondrogen, in 2008. Under the terms of the deal Osiris received $130 million up front and could be due to receive another $1.25 billion in milestone payments. The firm retains commercialization rights to Prochymal and Chondrogen in the U.S. and Canada. Genzyme’s rights span the rest of the world, except Japan, where JCR Pharmaceuticals holds rights to Prochymal for the treatment of hematological malignancies

At the end of April Osiris received a $1 million milestone payment from JCR relating to advances in Prochymal development in Japan for the treatment of acute GvHD. In February the firm reported positive data from a Phase III trial evaluating Prochymal in difficult-to-treat steroid-refractory GvHD. The data showed Prochymal therapy significantly improved response in steroid-refractory liver and gastrointestinal GvHD. In the sickest patients with GvHD affecting skin, liver, and gastrointestinal tract, treatment with Prochymal resulted in a 63% overall response rate. None of the placebo-treated patients responded

The firm separately reported on a new study evaluating Prochymal as a rescue therapy in children suffering from severe treatment-resistant graft vs. host disease. The data demonstrated that Prochymal achieved an overall response rate of 63% and improved survival rates.

Previous articleRedHill Biopharma to Market and Sell SCOLR Pharma’s Ondansetron Product
Next articleIntercell Buys Cytos’ mAb Discovery Platform for €15M