Osiris Resumes Enrollment in Stem Cell Trial for Crohn's Disease Following Positive Interim Analysis
COLUMBIA, Md., May 05, 2010 (BUSINESS WIRE) -- Osiris Therapeutics, Inc. (NASDAQ:OSIR) today announced that it is resuming enrollment in its clinical trial evaluating Prochymal for patients with treatment-resistant Crohn's disease. The findings of an interim analysis showed that for the primary endpoint of disease remission, Prochymal is approaching statistical significance in the intent to treat (ITT) population, and has reached significance in the per protocol population. Additionally, the analysis showed that Prochymal continued to demonstrate a benign safety profile with no significant differences in any of the pre-defined safety outcomes compared to placebo.
The Crohn's program consisted of two linked trials - one aimed at inducing remission (Protocol 603) and the other at maintaining response (Protocol 610) in patients who had failed other available treatments for the disease. Enrollment was suspended in 2009 over concerns the trial design would make it difficult to detect a treatment effect. The trial remained blinded, however, to permit an interim analysis of all 207 patients enrolled in the study. The results showed that despite the initial concerns, the effect size, or difference between the Prochymal and placebo response rates, of one dose arm of Prochymal is consistent with the original statistical assumptions of the protocol and is significantly outperforming placebo.
The decision to resume enrollment was made following discussions with the Food and Drug Administration (FDA) about the results of the interim analysis. Enrollment will now continue with the best-performing Prochymal dose arm and the placebo arm, according to the pre-specified adaptive trial design. The trial has been repowered to compensate for the statistical penalty incurred by the interim analysis in the ITT population. The follow-on maintenance trial (Protocol 610) has been discontinued to remove the potential for bias.
"We are encouraged by the robust results for the primary endpoint of disease remission from the 207 patients evaluated thus far," said Douglas Jacobstein, M.D., Pediatric Gastroenterologist and Medical Director of the Crohn's program at Osiris Therapeutics. "We will have a better understanding of the benefits Prochymal may offer to patients with treatment-resistant Crohn's disease after enrollment has been completed and the full data set has been thoroughly analyzed. 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."
The trial is evaluating patients with severe Crohn's disease that is not responsive to treatment with steroids, immunomodulators (azathioprine, 6-mercaptopurine, and methotrexate), and biologic agents (Remicade(R), Humira(R), and Cimzia(R)). The majority of patients enrolled thus far have failed at least two immunomodulators and two biological agents. Patients are required to complete a "washout" period prior to study entry to ensure that residual benefit from prior therapy does not influence their response. There were no differences in average Crohn's Disease Activity Index (CDAI) scores at entry, which exceeded 350 in all arms prior to treatment, indicating the patients had very debilitating disease.
The primary endpoint for Protocol 603 is the proportion of patients experiencing disease remission within 28 days of initiation of therapy with Prochymal, compared to those patients receiving placebo. For a patient to reach the primary end-point of disease remission, their CDAI score must fall to below 150.
About Prochymal
Prochymal is a preparation of mesenchymal stem cells (MSCs) formulated for intravenous infusion. The MSCs utilized in Prochymal are isolated from the bone marrow of healthy young adult donors, avoiding the controversy surrounding embryonic and fetal cell sources. They are grown in culture, permitting large-scale production. Because the cells can be expanded, thousands of doses can be produced from a single donation. Studies suggest MSCs are able to safely facilitate tissue repair through a number of mechanisms. Specifically, these studies indicate that MSCs are able to down-regulate severe inflammation and work at the cellular level to rebuild damaged tissue through the coordinated release of tissue-specific growth factors.
Prochymal is being evaluated in clinical programs for graft versus host disease (GvHD), Crohn's disease, acute myocardial infarction, pulmonary disease and type 1 diabetes. Prochymal has been granted Fast Track status by the FDA for GvHD and Crohn's disease, and is the first stem cell product to receive FDA expanded access approval, making the product available now to patients with life-threatening GvHD. Prochymal also obtained Orphan Drug status for GvHD and type 1 diabetes from the FDA, as well as Orphan Drug status for GvHD from the European Medicines Agency.
http://www.osiris.com
COLUMBIA, Md., May 05, 2010 (BUSINESS WIRE) -- Osiris Therapeutics, Inc. (NASDAQ:OSIR) today announced that it is resuming enrollment in its clinical trial evaluating Prochymal for patients with treatment-resistant Crohn's disease. The findings of an interim analysis showed that for the primary endpoint of disease remission, Prochymal is approaching statistical significance in the intent to treat (ITT) population, and has reached significance in the per protocol population. Additionally, the analysis showed that Prochymal continued to demonstrate a benign safety profile with no significant differences in any of the pre-defined safety outcomes compared to placebo.
The Crohn's program consisted of two linked trials - one aimed at inducing remission (Protocol 603) and the other at maintaining response (Protocol 610) in patients who had failed other available treatments for the disease. Enrollment was suspended in 2009 over concerns the trial design would make it difficult to detect a treatment effect. The trial remained blinded, however, to permit an interim analysis of all 207 patients enrolled in the study. The results showed that despite the initial concerns, the effect size, or difference between the Prochymal and placebo response rates, of one dose arm of Prochymal is consistent with the original statistical assumptions of the protocol and is significantly outperforming placebo.
The decision to resume enrollment was made following discussions with the Food and Drug Administration (FDA) about the results of the interim analysis. Enrollment will now continue with the best-performing Prochymal dose arm and the placebo arm, according to the pre-specified adaptive trial design. The trial has been repowered to compensate for the statistical penalty incurred by the interim analysis in the ITT population. The follow-on maintenance trial (Protocol 610) has been discontinued to remove the potential for bias.
"We are encouraged by the robust results for the primary endpoint of disease remission from the 207 patients evaluated thus far," said Douglas Jacobstein, M.D., Pediatric Gastroenterologist and Medical Director of the Crohn's program at Osiris Therapeutics. "We will have a better understanding of the benefits Prochymal may offer to patients with treatment-resistant Crohn's disease after enrollment has been completed and the full data set has been thoroughly analyzed. 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."
The trial is evaluating patients with severe Crohn's disease that is not responsive to treatment with steroids, immunomodulators (azathioprine, 6-mercaptopurine, and methotrexate), and biologic agents (Remicade(R), Humira(R), and Cimzia(R)). The majority of patients enrolled thus far have failed at least two immunomodulators and two biological agents. Patients are required to complete a "washout" period prior to study entry to ensure that residual benefit from prior therapy does not influence their response. There were no differences in average Crohn's Disease Activity Index (CDAI) scores at entry, which exceeded 350 in all arms prior to treatment, indicating the patients had very debilitating disease.
The primary endpoint for Protocol 603 is the proportion of patients experiencing disease remission within 28 days of initiation of therapy with Prochymal, compared to those patients receiving placebo. For a patient to reach the primary end-point of disease remission, their CDAI score must fall to below 150.
About Prochymal
Prochymal is a preparation of mesenchymal stem cells (MSCs) formulated for intravenous infusion. The MSCs utilized in Prochymal are isolated from the bone marrow of healthy young adult donors, avoiding the controversy surrounding embryonic and fetal cell sources. They are grown in culture, permitting large-scale production. Because the cells can be expanded, thousands of doses can be produced from a single donation. Studies suggest MSCs are able to safely facilitate tissue repair through a number of mechanisms. Specifically, these studies indicate that MSCs are able to down-regulate severe inflammation and work at the cellular level to rebuild damaged tissue through the coordinated release of tissue-specific growth factors.
Prochymal is being evaluated in clinical programs for graft versus host disease (GvHD), Crohn's disease, acute myocardial infarction, pulmonary disease and type 1 diabetes. Prochymal has been granted Fast Track status by the FDA for GvHD and Crohn's disease, and is the first stem cell product to receive FDA expanded access approval, making the product available now to patients with life-threatening GvHD. Prochymal also obtained Orphan Drug status for GvHD and type 1 diabetes from the FDA, as well as Orphan Drug status for GvHD from the European Medicines Agency.
http://www.osiris.com