Why did the U.S. FDA decline to review the new mRNA influenza vaccine?

On February 3, 2026, the US FDA issued a ‘refusal to file’ (RTF) letter to Moderna Inc. regarding their new mRNA vaccine developed against influenza. This decision generated considerable controversy worldwide, particularly given the current direction of vaccination policy in the United States towards a more conservative approach. However, that does not necessarily mean that the FDA’s refusal of a new mRNA influenza vaccine is connected to this policy shift.

Let us examine the facts.

How mRNA tech works

The new vaccine, named mRNA-1010, was developed by Moderna Inc., which also made an mRNA-based COVID-19 vaccine taken by millions of people worldwide during the pandemic (mRNA vaccines were not part of India’s mass vaccination programme). While most conventional viral vaccines insert actual pieces of a virus into the body, mRNA technology involves injecting “instructions” that signal our cells to produce a specific viral protein. The immune system then recognises this protein and mounts a response — without all the risks associated with an actual infection. As with other vaccines, this immune response may prevent or at least blunt a future infection. The advantage of mRNA technology, in the context of influenza, is that as viruses change their structure, vaccine design can be modified quickly to match the latest strains. In the event of an entirely new or novel virus emerging, the platform allows for relatively rapid development, offering a chance to limit the spread of future pandemics.

The success of mRNA vaccines during COVID-19 formed the basis of the, 2023 Nobel Prize in Physiology or Medicine recognising foundational work in mRNA technology that had been in development for decades. It was only expected that the same platform would be used to create new influenza vaccines. Influenza causes significant global illness and death each year, particularly among older individuals.

Vaccination reduces hospitalisation, death and even cardiovascular complications such as heart attacks and strokes. Annual vaccination is considered necessary because circulating viral strains continue to change, sometimes to such an extent that vaccines given in anticipation may not perfectly match strains that circulate later in the year. An mRNA-based influenza vaccine offers the theoretical advantage of faster strain updates.

Why was the refusal issued

Moderna is also developing a combined influenza and COVID-19 mRNA vaccine, and regulatory success of such a combination product in the U.S. may depend on approval of its standalone influenza component. The reasons for the decision are stated in the letter signed by Vinayak Prasad, Director of the FDA’s Center for Biologics Evaluation and Research. The agency issued a “refusal to file” because the application did not contain what it considers an “adequate and well-controlled” trial. Specifically, the control group used in the clinical study did not reflect what the FDA considers the “best available standard of care” in the United States for individuals aged 65 years and above.

The standard influenza vaccine contains 15 micrograms of antigen per strain. In contrast, older adults commonly receive high-dose influenza vaccines containing 60 micrograms per strain — four times the antigen amount. Alternatively, adjuvanted vaccines are used to enhance immune response in this age group. These enhanced vaccines are recommended because immune responses decline with age. The comparator used in the mRNA-1010 trial was a standard-dose (15 micrograms) quadrivalent influenza vaccine, commonly administered to younger adults.

Although also licensed for older individuals, it is not generally considered the preferred option in that age group when enhanced vaccines are already available. The FDA’s position was that if the new mRNA vaccine was intended for use in older adults, it should have been compared against a high-dose or adjuvanted vaccine that better reflects current clinical practice. By using a standard-dose comparator, the study may not have answered the relevant clinical question: how does the new vaccine perform against the strongest available alternatives? Controversy aside, it is important to understand what this decision does not represent: it is not a rejection of the mRNA platform. It is not a declaration that the vaccine is unsafe. It is not a statement that the mRNA influenza vaccine does not work.

Further options

Instead, the FDA stated that it “does not consider the application to contain a trial ‘adequate and well-controlled’ and is therefore, on its face, inadequate for review.” In regulatory language, this means the agency judged that the submitted study design itself failed to meet the evidentiary threshold required to proceed to full evaluation. The FDA letter outlines further procedural options available to the company, including a formal meeting to resolve the issue or the possibility of requesting that the application be reviewed despite the agency’s objections.

A third option is conducting a new study, but using a stronger comparator. However, performing a new head-to-head study against a higher-dose vaccine would involve additional cost and time, as well as the real possibility that the new vaccine may not demonstrate clinical superiority over existing alternatives.

The company had earlier published an immunogenicity study demonstrating a stronger antibody response for the mRNA-1010 vaccine, compared with both standard and high-dose influenza vaccines.

That study did not assess vaccine effectiveness in preventing disease. However, in the subsequent phase 3 study evaluating vaccine effectiveness in preventing influenza, the company chose to compare against the standard dose vaccine—and not the high dose vaccine. In that study, the rate of laboratory-confirmed influenza was about 26.6% lower in those who received the mRNA vaccine compared with those who received a standard-dose flu shot.

What next

This is encouraging — but it is unclear whether it would perform better than the stronger high-dose or adjuvanted vaccines commonly given to older adults. In that sense, the FDA’s position appears straightforward. When entering a mature vaccine space where improved options already exist for older adults, comparison against the strongest available alternative becomes important. This principle extends beyond vaccines to the evaluation of new treatments for conditions ranging from cancer and hypertension to stomach ulcers.

Thus, the controversy surrounding this decision may be loud, but the scientific reasoning outlined in the letter is clear and specific. In summary, the debate here is not about the legitimacy of mRNA vaccines. It is about whether the right comparator was chosen in a clinical trial — and whether that design is sufficient for regulatory review. Demanding tighter standards for clinical trials before regulatory approval strengthens public confidence and safety in the long run.

(Dr. Rajeev Jayadevan, is convener, research cell, Kerala State IMA and co-chairman, National IMA COVID Taskforce. rajeevjayadevan@gmail.com )

Published – February 13, 2026 06:07 pm IST