Hot Topic: Biomarkers and Accelerated Approval for Advanced Therapy

Over the past two years, the FDA has given accelerated approval (AA) to two advanced therapeutic products: Skysona (Bluebirds, 2022) and ELEVIDYS (Sarepta, 2023). This sets a significant precedent for the development of cell and gene therapeutic products (CGT) through the AA pathway for diseases beyond oncology.

The FDA established the AA pathway to expedite the approvall for drugs that treat serous conditions, based on a surrogate biomarker endpoint or an intermediate clinical endpoint. While Skysona is an autologous cell therapy approved for patients with Adrenoleukodystrophy (ALD), ELEVIDYS is an adeno-associated virus-based gene therapy for the treatment of pediatric patients with Duchenne muscular dystrophy (DMD). ALD and DMD are both devastating rare disorders that are idea targets for cell and gene therapy and are particularly suited for the AA pathway. Moreover, both are monogenic diseases, meaning their disease pathology arises from mutations in a single gene. Therefore, a primary disease activity biomarker (a direct measure of the core underlying disease biology) can be identified for these diseases. However, there are unsolved issues regarding what constitutes a primary disease activity biomarker, and if such biomarkers are reasonably likely predict of the clinical outcome and fulfill the surrogate requirement.

This session will leverage learnings from case studies of the recent CGT approvals through the AA pathway. We will explore the concepts of primary disease activity biomarkers, surrogate endpoints, and strategies that guide primary disease biomarkers towards surrogate endpoints. Short presentations will precede a panel discussion on the scientific, analytical, and regulatory challenges posed by an new drug development paradigm related to CGT approvals.