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

70628014This 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. 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. 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 cont