US FDA approves Moderna’s next-generation COVID-19 vaccine, with caveats

The US Food and Drug Administration has greenlit a next-generation COVID-19 vaccine from Moderna that’s engineered to be given in a smaller dose than the current one and targets certain portions of the SARS-CoV-2 spike protein. But only certain groups are approved to get the new vaccine.

The FDA approved mRNA-1283, marketed under the name mNEXSPIKE, for all adults 65 and older and 12- to 64-year-olds with at least one condition that puts them at risk for severe outcomes of COVID-19. The approval aligns with new regulatory framework outlined last month by FDA commissioner Marty Makary and Center for Biologics Evaluation and Research director Vinay Prasad.

“COVID-19 remains a serious public health threat, with more than 47,000 Americans dying from the virus last year alone,” Moderna CEO Stéphane Bancel says in a statement. “We appreciate the FDA's timely review and thank the entire Moderna team for their hard work and continued commitment to public health.”

The updated vaccine outperformed its predecessor, Spikevax, with one-fifth the dose in a Phase 3 clinical trial, Moderna said last June. Data from the trial have not yet been published in a peer-reviewed journal. The new formulation encodes two segments of the SARS-CoV-2 spike protein in messenger RNA (mRNA)—specifically, the receptor-binding domain and the N-terminal domain—which Moderna leaders say elicit the most-effective antibodies against COVID-19. In contrast, Spikevax encodes the whole protein.

In the Phase 3 study, mRNA-1283 met its primary goal of showing noninferior efficacy compared with Spikevax, and it was actually more effective than Spikevax in adults, according to Moderna. The trial enrolled about 11,400 people aged 12 years and older, half of whom received mRNA-1283 and half of whom received Spikevax.

Newly appointed leaders at the FDA and other agencies of the US Department of Health and Human Services (HHS) have called for placebo-controlled trials of COVID-19 vaccines. Makary and Prasad recommend testing the vaccines in 50- to 64-year-olds without risk factors for severe COVID-19, which would take place after the shots are formally approved (N. Engl. J. Med. 2025, DOI: 10.1056/NEJMsb2506929). For younger people without risk factors, Makary and Prasad encourage manufacturers to run and submit data from randomized controlled trials.

Back in 2020, when COVID-19 vaccines were first created, scientists did test them against placebos. But ethics experts say it would be wrong to do so today, since COVID-19 vaccines are widely available and protect against the worst outcomes of the disease. It’s standard to measure new and updated vaccines against the original shots.

HHS leaders cite a lack of clinical data around COVID-19 boosters as reason for recent policy changes. Last week, HHS Secretary Robert F. Kennedy Jr. announced that the Centers for Disease Control and Prevention (CDC) would no longer recommend COVID-19 vaccines for children or pregnant people without health conditions that place them in a high-risk category, but the CDC contradicted his announcement days later. The agency updated the childhood immunization schedule to allow for “shared clinical decision-making”—effectively, if a parent wants their child to be vaccinated, that child can get a COVID-19 vaccine “informed by the clinical judgment of a healthcare provider.”

For Moderna, the federal government’s shift in attitude toward vaccines has taken a toll on other vaccine candidates it is developing. The firm is working on a combination shot that contains mRNA-1283 and a seasonal flu vaccine called mRNA-1010.

The company had submitted an application for the combination vaccine to the FDA but pulled it on May 21, saying it would wait until efficacy data from mRNA-1010's Phase 3 trial are available later this year. The new FDA rules for COVID-19 vaccines add another layer of complexity: as Leerink Partners stock analyst Mani Foroohar points out in a research note, “it’s not entirely clear whether the combo will have to meet the burden of proof established in the flu framework, COVID framework, or eventually be evaluated on a separate framework.”

The combination shot had been a lynchpin in Moderna’s strategy for business growth, since COVID-19 vaccine sales have waned dramatically in the past few years. A two-in-one vaccine would present a unique advantage, allowing people who are already used to getting an annual flu shot to easily opt in to getting an annual COVID-19 shot as well.

Meanwhile, just last week, the federal government canceled $766 million in funds that the Biomedical Advanced Research and Development Authority (BARDA) had granted Moderna to develop an mRNA vaccine against pandemic flu—including avian flu, which continues to circulate among birds and dairy cattle and has infected 70 people in the US.

The added financial strain may put more pressure on Moderna, which had already planned to cut costs by about $1 billion this year and $500 million next year.