Combination Flu/COVID Vaccines Face Regulatory Hurdles as Industry Navigates New Landscape

The pharmaceutical industry is grappling with evolving regulatory requirements for combination flu/COVID-19 vaccines, as companies like Moderna, Pfizer, Novavax, and GeoVax navigate an uncertain path to market. Recent developments have highlighted the challenges facing vaccine makers in this new landscape, with stricter FDA guidelines and changing political attitudes shaping the future of vaccine development and approval.

Moderna's Setback and Industry-Wide Implications

Moderna's decision to withdraw its application for the mRNA-1083 combination flu/COVID-19 vaccine earlier this summer has sent ripples through the vaccine sector. The company pulled its biologics license application (BLA) after discussions with the FDA, which requested additional efficacy data for the flu component. This move has pushed back the estimated approval timeline from fall 2025 to 2026.

The FDA's request for more comprehensive data signals a shift in the regulatory approach to combination vaccines and novel technologies like mRNA. Myles Minter, an analyst at William Blair, noted, "It's a lot of moving parts, purely from a regulatory point of view."

Moderna has since released Phase III results showing its flu vaccine component outperformed current standards by 26.6% in preventing disease in adults aged 50 years or older. However, the company has not yet announced a BLA resubmission.

New Regulatory Landscape and Industry Adaptation

The FDA has recently made several announcements regarding the approval process for new vaccines and seasonal updates. These changes include requiring saline placebos in clinical trials and emphasizing the need for efficacy data rather than just immunogenicity data.

FDA officials Vinay Prasad and Marty Makary have indicated that immunogenicity data alone would only be sufficient for approval in high-risk populations. For healthy populations, the agency now requires efficacy data from randomized, placebo-controlled trials.

This stricter guidance has already impacted other vaccine manufacturers. Novavax, for instance, faced delays in the full approval of its protein-based COVID vaccine, Nuvaxovid. Silvia Taylor, executive vice president at Novavax, commented on the surprise restrictions: "I think it was a matter of timing. April 1 was our PDUFA and that was the date that Prasad started. It makes sense that somebody new comes in and says, 'hold on, I have an opinion here.'"

Industry Response and Strategic Shifts

Vaccine developers are adapting their strategies in response to these regulatory changes. Novavax has paused work on its flu-COVID combination vaccine until it can secure a development partner. However, the company's COVID-19 vaccine partner, Sanofi, is using Novavax's Matrix-M adjuvant in two flu/COVID-19 combo vaccines, providing "multiple shots on goal," according to Taylor.

GeoVax, which develops vaccines using virus-like particles, is prioritizing individual shots over combination vaccines for the time being. CEO David Dodd explained, "We see a combo flu/COVID vaccine as a 4-5 antigen vaccine."

Companies are also considering the potential impact of Health Secretary Robert F. Kennedy Jr.'s views on vaccine development. Kennedy has expressed a preference for multi-antigen vaccines over single-antigen approaches, adding another layer of complexity to the regulatory landscape.

As the industry navigates these challenges, frequent communication with drug regulators at HHS and the FDA remains crucial. Dodd emphasized, "Our philosophy is very simple: regardless of what one's political views might be, at the end of the day all of us in the industry have to work in the environment that we have."

Despite the current hurdles, industry analysts remain cautiously optimistic about the long-term prospects for combination vaccines. As Minter concluded, "One consistent message from Prasad: if you do the trial and show it works in the target population you're asking for approval for, we're going to review the data. I have to assume that ends in approval."