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FDA Outlines 'Plausible-Mechanism' Pathway to Speed Bespoke Therapies

The plan would shift initial proof to small, well-characterized patient cases with real-world follow-up required.

Overview

  • In a New England Journal of Medicine essay, FDA leaders Marty Makary and Vinay Prasad detailed a pathway allowing marketing authorization after success in several consecutive patients rather than randomized trials.
  • Approvals would rest on biological plausibility and confirmed target engagement alongside clinical improvement, supported by well-characterized historical data on the disease course.
  • The agency says it will prioritize rare conditions that are fatal or cause severe childhood disability, with possible consideration for some common diseases lacking proven treatments.
  • Companies granted authorization would be required to collect real-world evidence over time to confirm sustained benefit and monitor for safety, including developmental effects in children.
  • Officials cited the rapid, single-patient CRISPR case of an infant known as KJ as an illustrative example and noted the framework could extend beyond gene and cell therapies to small molecules and antibodies.