Overview
- The draft guidance outlines a route for genome-editing and RNA-based treatments to win approval for rare and ultra-rare conditions when randomized trials are not feasible.
- Sponsors must justify trial infeasibility, show that the therapy targets the causal abnormality, leverage natural-history data, demonstrate on-target activity, and present evidence of clinical benefit.
- Post-approval obligations include real-world evidence collection and confirmatory studies, with FDA warning it may withdraw products if commitments fail or results do not hold.
- The agency kept manufacturing standards unchanged and encouraged master protocols and shared evidence across related products to speed development.
- FDA opened a 60-day public comment period and expects a surge of applications, highlighting a CHOP/UPenn infant CPS1 case as a model and coming on the heels of moves to rethink the two-trial norm.