Comment from ALS Network
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Summary: The ALS Network, an organization serving people with ALS and their families, supports the FDA's draft guidance on the Plausible Mechanism Framework for individualized therapies. They argue that the framework should specifically include mutation-defined subsets of ALS while maintaining rigorous standards for biomarker validity, clinical evidence, safety monitoring, and confirmatory follow-up.
ALS Network respectfully submits the attached comments regarding FDA’s draft guidance on the Plausible Mechanism Framework for individualized therapies targeting specific genetic conditions with known biological cause.
As an organization serving people with ALS and their families across California, Hawaii, and beyond, ALS Network supports FDA’s effort to create a more practical pathway for therapies developed for very small, genetically defined patient populations. Our comments encourage FDA to ensure the final guidance can apply to mutation-defined subsets of ALS when the scientific criteria are met, while preserving strong expectations for biomarker validity, clinically meaningful evidence, confirmatory follow-up, natural history data, external controls, safety monitoring, and shared learning across ultra-rare therapeutic development.
We appreciate FDA’s consideration of these recommendations as it works to finalize the guidance.