What is the future of accelerated approval in rare diseases like...

What is the future of accelerated approval in rare diseases like DMD? Its rather topical and where better to go than straight to the horse's mouth. Reference is made to the recent article The future of accelerated approval for FDA's Marks? More rare disease drugs and no 'hanging chads' by Max Bayer published in Fierce Biotech.

Dr Peter Marks is a director of the FDA Center for Biologics Evaluation and Research. Marks outlines that the FDA have a better idea of the data they need to grant accelerated approvals and further indicates that more accelerated approvals could soon see the light of day. Importantly, we need to note two key points outlined by Marks;

• biomarkers or surrogate endpoints are easier to accrue than clinical endpoints
• biomarkers could relate to the expression of a particular protein

The proteomics analysis by ANP following the Phase 2 study in non ambulant patients with DMD revealed the modulation of key proteins known to impact TGF-β and the rate of loss of ambulation in DMD. For an explanation of the role of TGF-β and key protein expression, reference is made to the previously mentioned article Immune-mediated pathology in Duchenne muscular dystrophy by authors including members of the FDA Center for Drug Evaluation and Research.

The proteins modulated by ATL1102 in the Phase 2 study included LTBP4 and Thrombospondin. Now we know from the combination data in the recent animal model that MyoM1, a key skeletal muscle structural protein was increased by 33%.

Helpfully, Marks did mention that the FDA was capable of deciphering the science from both animal data and clinical studies. We now have a wish list of protein biomarkers following the database freeze and analysis on unblinded 6 month data.