When leadership changes at the FDA, as with Vinay Prasad succeeding Peter Marks, a core tension emerges. The new head isn't obligated to follow prior agreements, but abruptly shifting regulatory expectations for companies mid-development creates industry whiplash and erodes trust in the agency's consistency.

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 decision to block Moderna's application was made personally by CBER Director Dr. Vinay Prasad, against the recommendation of the FDA's vaccine office staff. This unusual top-down intervention bypasses standard scientific review processes, raising concerns about politicization and the integrity of the regulatory process.

Reporting reveals that FDA staff are fearful of Director Prasad due to his tendency to overturn scientific decisions and push out senior leaders. This environment stifles the voices of career scientists and has led to a "deleterious effect" on the center, potentially compromising the integrity of the review process.

Despite the FDA leadership co-authoring an editorial supporting single-trial approvals, the industry is skeptical. The agency's recent inconsistent actions mean no executive or investor can confidently build a development strategy or financial model based on this policy, rendering the announcement largely ineffective.

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.

Internal power shifts at the FDA, such as Vinay Prasad's rising influence, create a chilling effect on review teams. Even without direct orders, reviewers feel less emboldened to be flexible when leadership's public stance favors greater rigor. This 'tone from leadership' can shift regulatory outcomes more than explicit policy changes.

FDA CBER Director Vinay Prasad is reportedly overriding staff recommendations not just in his own center (vaccines), but also in CEDAR (drugs), as seen in the Disc Medicine case. This consolidation of decision-making power in one individual is making FDA approvals far more unpredictable for drug developers.

Recent events, like Moderna's rescinded 'refusal to file' letter, reveal that alignment with FDA staff on trial design is no guarantee. Senior leaders, notably Vinay Prasad, are reportedly overturning prior agreements, creating extreme uncertainty and making it impossible for companies to trust the regulatory guidance they receive.