Recent events, like Moderna's rescinded 'refusal to file' letter, reveal that alignment with FDA staff on trial design is no guarantee.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.
Related Insights
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.
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.
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.
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.
The FDA's quick reversal on reviewing Moderna's flu shot is not a simple policy change. It likely signals deep internal disagreements within the agency, potentially exacerbated by political pressure, which seeks to minimize vaccine-related news ahead of elections.
Moderna spent $1 billion on a trial based on FDA guidance that was later deemed unacceptable. This arbitrary "changing of the rules" after the fact makes long-term, capital-intensive investment in new medicines like vaccines extremely risky for pharmaceutical companies.
The FDA's "refuse to file" decision is highly unusual, occurring in only 4% of cases and typically for incomplete or flawed applications. Using it to block Moderna's submission over a previously-agreed-upon trial comparator suggests a strategic shift in regulatory posture, not a simple procedural issue.
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.
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.