Insufficient Early-stage EvidenceRegulators view early-stage data compared with external controls as insufficient to support a filing, creating major uncertainty unless new, more convincing confirmatory evidence is generated.
Safety And Dosing RisksDose-limiting toxicities, including liver enzyme elevations that prompted dosing pauses, raise concerns about dose selection, patient safety and the feasibility of larger pivotal studies.
Sham-controlled Trial RequirementFDA preference for a prospective, randomized, double-blind sham surgery-controlled trial would substantially increase trial complexity, extend development timelines and require significant additional capital.