Securing Accelerated Approval With a Failed Trial and Unproven Surrogate Endpoint

Situation

The pivotal trial in a rare neurodegenerative disease failed to meet its primary endpoint, and the sponsor chose to seek accelerated approval based on a novel biomarker that was not established as a surrogate endpoint reasonably likely to predict clinical benefit in this disease.

Strategy

We helped the sponsor team develop a strong argument for the validity of the surrogate endpoint by supplementing modeling data with a large body of literature linking the novel biomarker with clinical measures in the proposed indication and related neurodegenerative diseases.

We recommended that the sponsor present data demonstrating that failure on the primary clinical endpoint was due, in part, to the study design not adequately controlling for heterogeneity in the patient population. We also advised the sponsor team to leverage post hoc analyses showing that baseline levels of the biomarker were a reliable predictor of disease progression when used as a stratification factor.

We brought in a well-respected external KOL to help make the case that the treatment effects observed in the pivotal trial were clinically meaningful.

Results/Outcome

The advisory committee voted unanimously in favor of Accelerated Approval, and this first-in-class drug was approved for use, giving hope to patients and their families dealing with a devastating neurodegenerative disease. The advisory committee also indicated that the ongoing confirmatory trial will be important to validate the surrogate endpoint.