After receiving a letter directly from CBER Director Vinay Prasad, Moderna said the FDA had previously signed off on the use of a licensed flu vaccine as a comparator for a Phase 3 study of mRNA-1010.
The FDA has declined to even consider Moderna’s application for the investigational mRNA flu vaccine mRNA-1010, a move that comes amid controversial immunization policies from the Trump administration.
The refusal-to-file letter (RTF) was signed by Center for Biologics Evaluation and Research (CBER) Director Vinay Prasad himself, who has been vocal about tightening regulations on vaccines. In the RTF, the regulator claimed that Moderna failed to support mRNA-1010’s application with an “adequate and well-controlled” trial, according to the company’s Tuesday news release. Specifically, Moderna’s comparator group “does not reflect the best-available standard of care,” Prasad said in the letter, which Moderna published in full on its website.
In a statement on Monday, CEO Stéphane Bancel hit back at the FDA’s decision to refuse a review: “This decision by CBER, which did not identify any safety or efficacy concerns with our product, does not further our shared goal of enhancing America’s leadership in developing innovative medicines.”
William Blair analysts said the rebuff represents a major blow to the already struggling vaccine maker’s financial goals. “The RTF letter for mRNA-1010 represents a big hit to the company’s vaccine franchise and its prospect of achieving its breakeven guidance in 2028,” the analysts wrote in a Wednesday morning note.
Moderna’s shares were down 10% $37.76 in premarket trading Wednesday morning.
And it’s not just mRNA-1010 that could be affected by the FDA’s decision, with analysts at Jefferies noting that the RTF could impact the timing of a potential U.S. refiling of mRNA-1083, Moderna’s combination shot for COVID-19 and flu.
In May 2025, the company pulled its approval application for mRNA-1083 and decided to wait for data from mRNA-1010 before resubmitting. The company, Jefferies said on Tuesday, was “planning to seek [additional] FDA guidance” after the mRNA-1010 submission. But after the RTF, the path forward could change, Jefferies speculated in a note to investors.
William Blair agreed. “We will know more after the Type A meeting minutes are issued, but this is a substantial hit to the probability of success for mRNA-1010, and in turn mRNA-1083’s (combo flu/COVID vaccine) U.S. approvability, in our view.”
Moderna backed its application for mRNA-1010 with several late-stage studies, the company said last month. One of which, announced in June 2025, compared the investigational shot against a currently licensed, standard-dose seasonal flu vaccine. Data showed that Moderna’s candidate was 26.6% more effective than the comparator vaccine at preventing flu in adults 50 years and up.
The company pointed out in its news release that the FDA’s own regulation on the use of adequate and well-controlled studies, as well as guidance for flu vaccine development, do not “contain any reference to the use of a comparator reflecting the ‘best-available standard of care.’”
Moderna likewise argued that the refusal “is inconsistent with previous written communications” with CBER, which had found a standard-dose flu shot to be an “acceptable” comparator. “It should not be controversial to conduct a comprehensive review of a flu vaccine that uses an FDA-approved vaccine as a comparator in a study that was discussed and agreed on with CBER prior to starting,” Bancel said in his statement.
The Department of Health and Human Services (HHS) announced in May 2025 that all new vaccines would require placebo-controlled trials, a move that experts widely questioned. “HHS’s judgment appears questionable and risky, in our view,” Leerink Partners wrote at the time, adding that “placebo-controlled trials are unnecessary and unethical for many populations.”
In a statement to STAT News, a spokesperson for the Department of Health and Human Services said that “the FDA generally does not comment on regulatory communications to individual sponsors.”
Tuesday’s rebuff to Moderna compounds the already-mounting worries that vaccine developers face in the U.S., fueled largely by controversial policies under the Trump administration. In addition to the new placebo requirement, Prasad suggested the agency would enact stricter regulations for COVID-19 vaccines, after falsely claiming that at least 10 children had died from the shots.
Over at the CDC, recommendations for vaccine use have also been shifting. Last month, the agency unilaterally scrapped the recommendation that children be immunized against flu and five other diseases. In December 2025, the CDC also pushed back infant hepatitis B vaccination from being given at birth to two months of age.
As a result of these policy headwinds, Moderna announced late last month that it will no longer invest in Phase 3 vaccine studies—though it remains unclear if this directive will only affect its infectious disease programs or will apply broadly to its entire vaccine portfolio.
“You cannot make a return on investment if you don’t have access to the U.S. market,” Bancel told Bloomberg at the time.