The Food and Drug Administration announced on Mar. 12 new draft guidance to encourage greater data sharing in the cell and gene therapy field, aiming to streamline development for individualized genetic medicines targeting rare diseases. However, recent regulatory decisions have led some industry leaders to question how consistently this flexibility will be applied.
The draft guidance outlines a “plausible mechanism” review pathway that encourages sponsors to use shared datasets, natural history evidence, and prior program knowledge. Despite this, the FDA recently declined accelerated approval for REGENXBIO’s Hunter syndrome gene therapy due to insufficient evidence and told uniQure its Huntington’s disease therapy would require a new trial with a sham surgery control group instead of relying on existing Phase 1/2 data supported by external controls.
Robin Muthig, senior director at the Alliance for Regenerative Medicine (ARM), said in a prepared statement: “While we were pleased to see the FDA’s guidance for the plausible mechanism framework, and will be submitting comments on the draft, this meaningful step cannot distract from recent FDA regulatory surprises in which the agency reversed course on previous commitments for rare disease programs that could help thousands of patients right now.”
The FDA has previously released several draft guidances aimed at making trial designs more flexible and encouraging real-world evidence use while maintaining quality controls. The plausible mechanism pathway is intended to allow sponsors to leverage existing data when traditional randomized trials are not feasible. The agency wrote in its latest draft: “Sponsors should seek early feedback on their nonclinical development plans to discuss data leveraging opportunities specific to their program. Shared learning through appropriate data sharing is one opportunity to facilitate continued research.”
Despite these efforts, industry experts say actual data sharing remains limited due to concerns about competitive advantage. Jon Ellis, CEO of Trenchant Bio, told BioSpace: “There is little to no data sharing occurring today.” David Barrett, CEO of the American Society of Gene and Cell Therapy (ASGCT), said clear standards are needed: “You can’t share what you can’t capture.”
Recent studies show inconsistencies in submitted clinical trial data between regulators such as the FDA and European Medicines Agency. During an FDA public meeting last fall, patient advocates like Kelly Brazzo highlighted that fragmented data delays access to therapies: “Sharing of data—on data collection processes, on trial designs, on manufacturing, on any serious adverse events—reduces duplication and can ultimately save time and muscle for our patients.”
Stephen Majors, VP at ARM, questioned whether regulators will consistently accept natural history evidence instead of randomized trials under the new pathway. He said there appears to be "a huge disconnect or divergence" between recent regulatory decisions and the goals outlined in the plausible mechanism framework.
The FDA will accept public comments on its draft guidance until April 27.
