On Tuesday, Moderna received a refusal-to-file (RTF) letter from the U.S. Food and Drug Administration (FDA) for its mRNA flu vaccine candidate, mRNA-1010. The decision is part of a broader pattern that has emerged over the past year, with several biotechnology companies reporting reversals or changes in FDA guidance regarding evidence required for product approvals.
Moderna CEO Stéphane Bancel commented on the agency’s action: “It should not be controversial to conduct a comprehensive review of a flu vaccine submission that uses an FDA-approved vaccine as a comparator in a study that was discussed and agreed on with CBER prior to starting.”
Executives at other biotech firms such as Capricor Therapeutics, uniQure, and Biohaven have also faced challenges after the FDA reversed earlier agreements about what data would be needed for their products’ approval. These shifts have led to delays in timelines for treatments targeting Duchenne muscular dystrophy, spinocerebellar ataxia, and Huntington’s disease.
The Center for Biologics Evaluation and Research (CBER), which oversees biologic therapies including vaccines and gene therapies, has been identified by industry experts as the source of much regulatory confusion. During a panel discussion at Phacilitate’s Advanced Therapies Week in San Diego, Samar Mohanty, president & chief scientific officer at Nanoscope Therapeutics, said about the lack of clarity: “I can say definitely that’s not what the field in rare disease needs.” He noted that while CBER emphasizes evidence-based science and randomized control trials, this is not always feasible in rare diseases where previous guidance suggested biomarkers could suffice.
uniQure CEO Matt Kapusta expressed surprise when the company received feedback from the FDA indicating its single-arm study data might no longer be sufficient for accelerated approval—a reversal from guidance given just one year earlier.
Atara Biotherapeutics also reported similar issues when its T cell immunotherapy Ebvallo was turned back by the FDA despite previous alignment on trial design.
Roberta Duncan, former chief scientific officer at Arcturus Therapeutics, addressed another aspect during the panel: regulations and guidances are sometimes difficult to implement. She cited an article published in The New England Journal of Medicine outlining pathways for ultra-rare diseases but noted there remains “an inability to actually implement” these approaches effectively.
Despite these challenges, panelists generally agreed that the FDA is making efforts to balance safety with efficacy. Mohanty pointed out recent actions taken by regulators following adverse events linked to gene therapies as examples of robust pharmacovigilance. Michael Meyers of H.C. Wainwright added: “FDA is a good partner generally,” emphasizing his belief that applications are reviewed based on merit without undue political influence.
Duncan acknowledged improvements in communication between industry and regulators but suggested more accessibility would benefit companies navigating new therapies through approval processes. She compared her experience working with Japan’s Pharmaceuticals and Medical Devices Agency (PMDA), describing it as marked by continuous engagement and rapid feedback—something echoed by Mohanty regarding Japan's Ministry of Health interactions.
Panelists highlighted Japan's evolving regulatory approach as an example worth emulating due to its increased responsiveness compared to previous years.
BioSpace served as a media partner for Phacilitate’s Advanced Therapies Week event held February 9–12 at the San Diego Convention Center.
