Mesoblast has indicated that sufficiently strong Phase III data could reduce the development time required for its chronic heart failure (CHF) stem cell candidate Revascor (immunoselected mesenchymal precursor cells [MPCs]), following communication with the US Food and Drug Administration (FDA). During a meeting with Mesoblast’s developmental partner Teva, the FDA suggested the possibility of early trial completion if “overwhelming” efficacy is demonstrated. Revascor is currently the most advanced regenerative therapy in development for CHF, so strong clinical data and early trial completion would further enhance the drug’s commercial potential.
Revascor is being studied for end-stage CHF patients for whom no effective treatment currently exists. The drug is a platform technology which increases blood flow and stimulates growth, and the technology is based on the regenerative properties of allogeneic MPCs.
Teva plans to reduce the number of patients in Revascor’s trials from 1,730 to 1,165 and perform an interim analysis of the data. The analysis would test for the superiority of the data produced when 50% of heart failure-related major adverse cardiovascular events (HF-MACEs) have occurred. Datamonitor Healthcare believes that Teva should continue with the larger sample, despite the clear financial benefits of using a smaller population. A larger sample size could strengthen the clinical significance of Revascor’s data, enabling a stronger New Drug Application, and it could also be helpful in monitoring the drug’s effects post-marketing, given that Revascor would represent a novel therapy class in CHF treatment.
A planned confirmatory study with a primary endpoint of recurrent HF-MACE may further strengthen Revascor’s clinical potential by dampening concerns over trial design. Composite endpoints such as HF-MACE used by the current study have inherent flaws; this approach does not account for the severity of adverse events included within the composite endpoint, and recurrence of HF-MACE is not accounted for. Using recurrent HF-MACE as a primary endpoint would address these flaws by recognizing multiple MACE, further improving Revascor’s clinical data.