The biotech industry underestimated how a new political administration would impact the mRNA space. The change in leadership led to significant regulatory uncertainty and a general risk aversion towards mRNA technology, which in turn suppressed faith and funding despite the platform's recent successes.

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.

Despite massive turnover and internal dysfunction at the FDA, biotech investors have largely shrugged off the regulatory uncertainty. This disconnect suggests the market believes the negative impacts, like drug review delays, are a lagging indicator that won't materialize immediately, creating a potential future risk for the sector.

Amidst growing turmoil at the FDA, a viable strategy is to "invest around" the risk. This involves prioritizing companies whose drugs show clear data on well-understood, validated endpoints, as these are most likely to navigate the current political environment successfully, regardless of leadership changes.

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.

The resignation of key figures like Peter Marks triggered a cascade of departures, leaving the FDA with a significant loss of long-term institutional knowledge. This creates uncertainty around the execution of new policies and guidance for the biopharma industry.

The replacement of CEDAR Director Richard Pazder with Tracy Beth Hoeg, who is viewed as an ideologue lacking regulatory experience, signals a shift toward politically driven decisions at the FDA. This move creates significant uncertainty and raises concerns that ideology, not science, will influence drug approvals.

The HHS Secretary's unprecedented interview of a candidate for FDA's CEDAR Director marks a significant politicization of a traditionally scientific, civil service position. This shift suggests future directors may need political alignment with the administration, leading to greater risk aversion, erratic decision-making, and less predictability for the biopharma industry.