FDA Commissioner Marty Makary publicly defended recent agency decisions to reject several rare‑disease therapies, citing cases where clinical benefit was not demonstrated and pushing back against accusations of undue caution. Makary’s remarks — including an anecdote about an intraventricular delivery approach that failed to show benefit — triggered investor concern and a sell‑off in some small rare‑disease developers, notably UniQure. UniQure’s shares plunged after markets interpreted Makary’s comments as targeting therapies using invasive delivery routes; the company noted Makary did not name UniQure specifically. Analysts cautioned that the comments underscore regulatory uncertainty in rare‑disease review standards and the difficulty in predicting approval outcomes for complex gene and cell therapies. Policy watchers and companies will monitor whether the agency clarifies standards for single pivotal trials, external control data, and real‑world evidence as debate intensifies over balancing speed and evidentiary rigor for ultrarare indications.