Unicure's experience reveals a significant regulatory risk: the FDA can reverse its position on a pre-agreed Statistical Analysis Plan (SAP). Despite prior alignment on using a natural history control, the agency later told the company this approach was merely 'exploratory,' invalidating their filing strategy and shocking investors.

A significant disconnect exists between the FDA leadership's public statements promoting flexibility and the stringent, delay-prone reality faced by companies. For areas like gene therapy, firms report feeling the "rug was pulled out," suggesting investors should be skeptical of the agency's accommodating PR.

The drama surrounding Sarepta's gene therapy, where a top regulator was ousted after political pushback and later reinstated, shows the FDA is now more amenable to outside influence. This case study indicates that presidential and activist pressure can directly impact regulatory enforcement and personnel decisions, moving beyond purely scientific considerations.

The FDA publicly champions rare disease drug development, but its actions—frequent and inconsistent rejections—tell a different story. This disconnect between rhetoric and reality creates significant uncertainty, causing prominent investors like Rod Wong of RTW Investors to reduce their investments in the space.

Unicure's setback with its Huntington's gene therapy demonstrates a new political risk at the FDA. A prior agreement on a trial's design can be overturned by new leadership, especially if the data is not overwhelmingly definitive. This makes past regulatory alignment a less reliable indicator of future approval.

An ideologically driven and inconsistent FDA is eroding investor confidence, turning the U.S. into a difficult environment for investment in complex biologics like gene therapies and vaccines, potentially pushing innovation to other countries.

Patient advocates for a Huntington's therapy are frustrated not just by the FDA's halt, but by its reversal on previously agreed-upon trial design. The agency initially accepted an external control arm but later deemed it inadequate, creating regulatory uncertainty that erodes trust and could chill future development in rare diseases.

Following its decision, FDA officials appeared on news channels and made pointed comments, including suggesting Moderna show "humility." This public relations offensive is unusual for a regulatory agency and serves as a warning to the industry, reflecting a newly adversarial relationship with developers.

The speaker's experience at a previous biotech highlights the extreme personal risk in the industry. After receiving a Complete Response Letter from the FDA, the entire commercial team that had been built in anticipation of a launch had to be let go, including the Chief Commercial Officer.