Comment from Cystic Fibrosis Foundation

Summary: The Cystic Fibrosis Foundation supports the FDA's draft guidance on the Plausible Mechanism Framework, particularly for its potential to facilitate the development of gene editing therapies for ultra-rare diseases. They request specific clarifications on population thresholds, the use of supplemental BLAs for adding variants, and the feasibility of observational run-in periods to ensure the framework remains practical for sponsors and patients.