The U.S. Food and Drug Administration (FDA) has declined to accept Moderna’s application for the review of its first mRNA seasonal flu vaccine, as confirmed by the company on Tuesday. This decision marks another challenge for mRNA technology, which has faced scrutiny from certain officials during the Trump administration.
The FDA communicated to Moderna that the application lacked an “adequate and well-controlled” clinical trial, primarily because the control arm did not meet the “best-available standard of care” in the U.S. at the time of the study. The company posted a letter, dated February 3, indicating that the agency did not raise any concerns related to safety or efficacy.
Moderna’s leadership expressed confusion over the FDA’s decision, arguing that it contradicts previous guidance they had received. Dr. Stephen Hoge, Moderna’s president, noted in an interview that no indication was given throughout the trial process that it was considered inadequate.
In response to the situation, the U.S. Department of Health and Human Services stated that the FDA usually refrains from commenting on discussions with individual applicants.
During a clinical trial involving 40,700 participants, Moderna used a standard-dose seasonal flu vaccine, Fluarix, as a comparator to illustrate the safety and efficacy of its mRNA vaccine. Although the FDA reportedly approved this approach in April 2024, it later suggested that data comparing Moderna’s vaccine to a high-dose flu vaccine for seniors should also be included, which the company claims it did.
Moderna highlighted that just months prior to the application submission, the FDA had implied they would review the filing, even hinting at potential issues regarding the comparator during the evaluation process. However, last week’s letter confirmed the agency’s decision to bypass the review entirely. Dr. Vinay Prasad, who oversees vaccine regulation at the FDA, signed the letter, having previously been critical of the government’s response to the COVID-19 pandemic.
Moderna, alongside Pfizer and Novavax, is one of three manufacturers of approved COVID-19 vaccines in the United States. Both Moderna and Pfizer utilize mRNA technology for their vaccines, with the latter also advancing mRNA-based flu vaccines.
Despite the rapid development of mRNA COVID-19 vaccines being a significant achievement during Trump’s administration, support for mRNA technology in other infectious diseases has waned. In August, HHS canceled 22 mRNA vaccine development projects, questioning their effectiveness against respiratory infections.
Proponents of mRNA technology argue that it could enhance seasonal flu vaccines, allowing for more tailored responses to circulating strains and potentially combining them with COVID-19 vaccines for streamlined vaccination. Currently, flu strains are selected months in advance, but mRNA offers the possibility of quicker responses to emerging strains.
Recent data from Moderna’s phase 3 study indicated that its mRNA flu vaccine demonstrated about 27% higher efficacy than Fluarix in participants aged 50 and older. Another trial comparing the experimental vaccine to a high-dose flu vaccine for individuals over 65 showed superior immune responses.
With the FDA review of its flu shot now on hold, Moderna has paused the progression of its combination flu and COVID-19 mRNA vaccine through the FDA review process. However, the combination vaccine continues to advance in other countries, with expectations for approval in Europe within the year, which would represent a significant milestone for the company.
