Moderna shares tumbled nearly 9 percent in premarket trading Wednesday after the Food and Drug Administration declined to review the biotechnology company’s application for approval of its experimental influenza vaccine, dealing a blow to efforts to diversify beyond declining COVID-19 revenue and raising questions about whether shifts in federal vaccine policy under Health Secretary Robert F. Kennedy Jr. contributed to the decision.
The FDA issued a refuse-to-file letter dated February 3 citing the lack of an “adequate and well-controlled” study with a comparator arm that “does not reflect the best-available standard of care,” according to Moderna’s regulatory filing. The letter, signed by Center for Biologics Evaluation and Research Director Vinay Prasad, did not identify safety or efficacy concerns with the mRNA-based influenza vaccine but said the clinical trial design failed to meet regulatory standards required to initiate formal review.
Moderna used Fluarix, a standard-dose quadrivalent flu vaccine manufactured by GlaxoSmithKline, as the comparator in its Phase 3 trial, a choice the FDA now says does not represent best available care despite Fluarix being widely used and recommended for certain age groups.
The regulatory rejection suggests the agency expected comparison against high-dose or adjuvanted flu vaccines that have demonstrated superior immune responses in older adults, though FDA guidance on acceptable comparators for mRNA flu vaccines has not been publicly clarified and Moderna said it followed established precedents for seasonal influenza vaccine development.
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The United States ended its longstanding childhood immunization guidance last month, removing recommendations that all children receive inoculations against influenza, hepatitis A, and other diseases, a policy reversal that public health officials warned could increase preventable illness and death while undermining decades of progress in controlling vaccine-preventable diseases.
The FDA’s refusal raises the risk of a more protracted U.S. regulatory path for both Moderna’s standalone flu shot and its combination influenza-COVID vaccine, which the company views as critical to sustaining revenue as demand for COVID-19 boosters collapses, Jefferies analysts said. Moderna generated nearly $18 billion in revenue in 2022 from its COVID-19 vaccine but has seen sales plummet as governments ended mass vaccination programs and most populations acquired immunity through infection or immunization. The company bet heavily that its mRNA platform, which enables rapid development of vaccines by encoding instructions for cells to produce viral proteins that trigger immune responses, could be adapted to seasonal influenza and other infectious diseases, creating a diversified product portfolio beyond COVID-19.
Stéphane Bancel, Moderna’s chief executive, said the company was “surprised and disappointed” by the FDA’s decision given the vaccine’s performance in clinical trials and believed the data submitted met regulatory standards.
“We remain confident in the science and the data package we submitted,” he said in a statement, adding that Moderna would engage with the FDA to understand specific concerns and determine the path forward for U.S. approval.
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The vaccine is currently under review in the European Union, Canada, and Australia, with potential approvals expected in late 2026 or early 2027 if regulators in those jurisdictions reach different conclusions about the adequacy of Moderna’s clinical evidence.
Several FDA-approved influenza vaccines, including products from AstraZeneca and Sanofi, are currently available in the United States, a competitive landscape that will complicate Moderna’s eventual market entry if it overcomes regulatory hurdles. High-dose and adjuvanted flu vaccines have captured growing market share in recent years based on evidence they provide superior protection for older adults compared to standard-dose formulations, a factor that likely influenced the FDA’s expectation for comparator selection even though regulatory guidance did not explicitly require such comparisons when Moderna designed its Phase 3 trial several years ago.
The refuse-to-file determination means the FDA will not initiate substantive scientific review of Moderna’s application until the company submits revised data addressing the agency’s concerns, a process that could require conducting additional clinical trials comparing the mRNA vaccine against high-dose or adjuvanted products, consuming years and hundreds of millions of dollars with no guarantee of ultimate approval.
Alternatively, Moderna could attempt to persuade regulators that its existing data package satisfies regulatory requirements through a different analytical framework, though the strongly worded rejection letter suggests limited room for reinterpretation without new evidence.
Investors reacted swiftly to the news, with Moderna shares falling from Tuesday’s close of $43.12 to below $40 in premarket trading Wednesday, a decline that erased approximately $2 billion in market capitalization and reflected concerns about both the specific flu vaccine program and broader challenges facing the company’s business model. Moderna’s stock has lost more than 80 percent of its value since peaking above $200 in 2021 during the height of COVID-19 vaccine demand, and the company has struggled to convince investors that its mRNA technology platform can generate sustainable profits across multiple therapeutic areas.
Whether Moderna can navigate the regulatory uncertainty and ultimately bring its influenza vaccine to U.S. market will test both the company’s technical capabilities and its ability to manage political headwinds that would have seemed implausible just years ago when mRNA vaccines were hailed as breakthrough technology that helped end the COVID-19 pandemic.