Robert Walker, MD
(Credit: Novavax)
The FDA has requested that Novavax complete an additional clinical trial for its COVID-19 vaccine, NVX-CoV2601, which it is seeking full approval for after it was granted an emergency use authorization in 2022.1 This news comes just days after the company received communication from the FDA asking for a postmarketing commitment (PMC) to generate additional clinical data.2
The company noted in a release on April 23 that it “believe[s] that our Biologics License Application (BLA) is approvable based on conversations with the US Food and Drug Administration, as of our Prescription Drug User Fee Act (PDUFA) date of April 1 and through today,” adding that it sought to move toward approval as soon as possible.
The company was previously awaiting feedback from the agency after the PMC. According to a report from the Wall Street Journal, this update comes after newly appointed members of the Department of Health and Human Services (HHS) intervened in the approval process.1 The agency’s request for new data does allow for Novavax to negotiate for a smaller and possibly less expensive study; however, doubts had been sown about the potential approval after the agency missed the April 1 PDUFA deadline. HHS Secretary Robert Kennedy Jr attributed the delay to the vaccine’s composition in an interview with CBS earlier this month.
Contagion spoke with Novavax’s Chief Medical Officer, Robert Walker, MD, in February 2025, discussing the company’s progress in obtaining full licensure for its COVID-19 vaccine, at which time Walker echoed the sentiment about the company’s hopes for approval, saying, “we’re very much looking forward to obtaining full licensure of our vaccine, achieving parity with the other COVID-19 vaccines available.” He added that the company was “working very closely with the FDA to make sure they get all their questions answered, and that they understand all the data we’ve provided in the application.”
Walker also issued a reminder about the importance of staying vigilant against COVID, which he said “is still very much with us,” adding that “it’s really important to protect ourselves, our families, and our communities. I encourage everyone to get vaccinated. If you’re in a high-risk group, make sure to get your revaccination. And above all, stay healthy.”
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Interim results from a phase 2/3 study of NVX-CoV2601 (NCT05975060) demonstrated significant improvements in immune response, suggesting its potential as an effective booster for adults in the US. The study was conducted between September 2023 and January 2024, showing that, based on a recombinant spike protein from the Omicron XBB.1.5 variant, the updated vaccine induced higher neutralizing antibody responses compared to the original NVX-CoV2373 formulation.4
That original NVX-CoV2373 vaccine was based on the first strain of COVID-19, while the updated NVX-CoV2601 was designed to target the Omicron XBB.1.5 variant that was circulating during the study. “Both vaccines should be classified the same—they are both COVID-19 vaccines. One is based on the original, more ‘prototype’ strain, while the other reflects the newer circulating strain at the time of the study,” Walker previously told Contagion.
The study involved 332 adults aged 18 years or older who had previously received 3 or more doses of mRNA vaccines, with participants receiving a single dose of NVX-CoV2601 via intramuscular injection. The primary end points were to demonstrate superiority in neutralizing antibody levels and non-inferiority in seroresponse rates compared to NVX-CoV2373. The study’s interim findings suggest that NVX-CoV2601 could serve as an effective booster, particularly for individuals who have received previous mRNA vaccinations.
Data showed a production of a geometric mean neutralizing antibody (nAb) titer of 905.9 at day 28, compared with 156.6 for the original NVX-CoV2373 formulation. The geometric mean titer ratio (GMTR) between the 2 groups was 5.8, indicating that the new vaccine generated significantly higher levels of neutralizing antibodies. As well, 64% of participants in the NVX-CoV2601 group showed a seroresponse, compared with just 7% for NVX-CoV2373.
Safety data from the study also supported the vaccine’s potential as a booster, with the most common adverse events (AEs; occurring within 7 days) included local reactions at the injection site (52% tenderness, 30% pain), fatigue (29%), and muscle pain (29%). Serious AEs were rare, with no deaths or severe events related to the vaccine. Unsolicited adverse events potentially linked to the vaccine occurred in only 2% of participants.
Walker noted that this manageable safety profile aligns with expectations for vaccines targeting new strains. “It’s not surprising that this combination continues to perform well, optimizing the immune response and, therefore, providing better protection over time.”
