The U.S. Food and Drug Administration (FDA) has requested that Novavax complete an additional clinical trial for its COVID-19 vaccine, NVX-CoV2601, before the agency will consider granting full approval. This development comes as a significant setback for the biotech company, which had been anticipating approval after receiving emergency use authorization (EUA) for its original vaccine formulation in 2022.
The FDA's request follows a missed Prescription Drug User Fee Act (PDUFA) date of April 1, after which Novavax received communication asking for a postmarketing commitment (PMC) to generate additional clinical data. The company had expressed confidence that its Biologics License Application (BLA) was approvable based on previous conversations with regulators.
Regulatory Complications and Political Context
According to reports from the Wall Street Journal, newly appointed members of the Department of Health and Human Services (HHS) may have intervened in the approval process. HHS Secretary Robert Kennedy Jr. attributed the delay to the vaccine's composition in a recent CBS interview.
While the FDA's request for new data does allow Novavax to negotiate for a potentially smaller and less expensive study, the additional requirements represent both a financial and strategic challenge for the company, which has been working to achieve parity with other fully approved COVID-19 vaccines on the market.
Promising Clinical Data for Updated Vaccine
Despite this regulatory hurdle, interim results from a phase 2/3 study of NVX-CoV2601 demonstrated significant improvements in immune response compared to the original formulation. The study, conducted between September 2023 and January 2024, evaluated the updated vaccine based on the Omicron XBB.1.5 variant.
The trial involved 332 adults who had previously received three or more doses of mRNA vaccines. Participants received a single dose of NVX-CoV2601 via intramuscular injection, with primary endpoints focused on neutralizing antibody levels and seroresponse rates.
Key findings from the study included:
- The updated vaccine produced a geometric mean neutralizing antibody titer of 905.9 at day 28, compared with 156.6 for the original NVX-CoV2373 formulation
- The geometric mean titer ratio between the two groups was 5.8, indicating significantly higher levels of neutralizing antibodies with the updated formula
- 64% of participants in the NVX-CoV2601 group showed a seroresponse, compared with just 7% for the original vaccine
Safety Profile and Adverse Events
Safety data from the study supported the vaccine's potential as a booster, with manageable side effects consistent with other COVID-19 vaccines. The most common adverse events occurring within seven days included:
- Local reactions at the injection site (52% tenderness, 30% pain)
- Fatigue (29%)
- Muscle pain (29%)
Serious adverse events 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.
Company Response and Future Outlook
Novavax's Chief Medical Officer, Robert Walker, MD, had previously expressed optimism about obtaining full licensure, stating 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 emphasized the continued importance of COVID-19 vaccination, noting that the virus "is still very much with us" and encouraging everyone, particularly those in high-risk groups, to get vaccinated or receive boosters as appropriate.
The FDA's request for an additional study introduces uncertainty into Novavax's timeline for full approval. The company will now need to determine the scope and design of the additional trial while continuing discussions with regulators about the path forward for its COVID-19 vaccine.
