Comment from Anonymous

Subject Comments on FDA Draft Guidance on the Plausible Mechanism FrameworkComments on FDA Draft Guidance on the Plausible Mechanism Framework ________________________________________ Dear FDA, I am a neurologist who frequently treats patients with highly aggressive brain tumors, and I am writing to provide comments on the FDA’s Draft Guidance, “Considerations for the Use of the Plausible Mechanism Framework to Develop Individualized Therapies that Target Specific Genetic Conditions with Known Biological Cause.” From a clinical perspective, the urgency of developing effective, individualized therapies for serious and life-threatening conditions and cancers cannot be overstated. Core Policy Goal It is important that the FDA ensure this pathway: •Is recognized as a valuable and innovative regulatory approach; •Applies beyond gene therapies to include cell therapies and other individualized treatment modalities; and •Maintains fairness across treatment types, so that no single modality receives a disproportionate regulatory advantage. Key Recommendation The pathway should clearly apply to any therapy that meets core scientific criteria, including: •A known genetic or biological target; •A personalized or individualized treatment design; and •Demonstrated ability to effectively address the relevant target. Regulatory policy should not limit this pathway to gene therapies alone. Instead, the framework should support innovation across a broad range of therapeutic platforms. Requested Clarification The Draft Guidance currently states that “the general concepts may apply to other types of individualized therapies” (lines 40–42). This language would benefit from stronger clarity. Specifically, replacing “may” with “apply” and explicitly stating “all” would make clear that the framework extends to all types of individualized therapies that meet the pathway’s requirements. This straightforward revision would help ensure that promising therapies—regardless of modality—can advance efficiently to patients in need. Conclusion This Draft Guidance represents an important step toward enabling faster development of individualized therapies, particularly for rare diseases and conditions with significant unmet need. Clarifying that the pathway applies broadly and equitably across treatment types will strengthen its impact and better support continued innovation. Thank you for the opportunity to comment. Sincerely, Anonymous