While former FDA official Vinay Prasad was known for his stringent reviews, the continued institutional skepticism towards Capricor's drug after his departure suggests the concerns were widespread among FDA staff. This indicates that attributing the FDA's recent restrictive stance solely to one individual's leadership style is an oversimplification of the agency's internal consensus on data quality.

The FDA publicly promotes regulatory flexibility for rare diseases, yet industry insiders perceive it as less permissive than prior administrations. This disconnect between the agency's messaging and its actual decisions is fueling widespread criticism, investor uncertainty, and accusations of 'moving the goalposts'.

The controversial approval of Elevidys has 'boxed in' the FDA. Now, when reviewing similar drugs like Regenexx Bio's, the agency must contend with its own precedent, making it difficult to apply a consistent standard and creating regulatory uncertainty for the entire field.

In response to emotional patient testimony supporting Capricor's Duchenne drug, an FDA official reframed regulatory strictness as a crucial patient safeguard. The argument is that high standards and rejecting drugs with weak data are essential to protect patients from the risks and false hope of ineffective treatments, turning a perceived barrier into a protective measure.

ODAC's critique of the SERENA-6 trial, focusing on immature overall survival (OS) data, contrasts sharply with previous landmark approvals like CDK4/6 inhibitors, which were approved without OS data. This suggests innovative, biomarker-adaptive trials may face a higher, potentially unfair, regulatory bar.

An FDA panel voted against Capricor Therapeutics' Duchenne drug, primarily because the company altered its statistical analysis plan after the study was complete but before unblinding. The FDA viewed this as a potential manipulation to achieve a more favorable outcome, critically undermining the credibility of the efficacy data presented.

After a decade on the market and multiple shifts in endpoints, Sarepta's definitive Phase 3 study for its DMD drugs failed. This outcome casts doubt on the entire accelerated approval framework for slowly progressive diseases, where surrogate endpoints may not translate to clinical benefit, leaving regulators and patients in a difficult position.

Previously considered a capital-efficient area due to regulatory flexibility, the rare disease and gene therapy space is now perceived as high-risk. The FDA is applying greater scrutiny and tightening standards, making development more unpredictable for sponsors.

Despite DINE Therapeutics presenting strong DMD data that surpasses historical benchmarks, investor confidence is weak. The FDA's recent unpredictable decisions in rare disease have created a perception that regulatory pathways are no longer reliable, even with compelling clinical results.