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

In a rapidly evolving regulatory environment, pharmaceutical companies developing combination influenza and COVID-19 vaccines are encountering unexpected challenges. The landscape for vaccine approvals has shifted, with stricter requirements and a new emphasis on efficacy data, leaving several major players reassessing their strategies.

Moderna's Setback and Industry-Wide Implications

Moderna's decision to withdraw its application for mRNA-1083, a combination flu/COVID-19 vaccine, has sent ripples through the pharmaceutical industry. The company had initially aimed for approval in time for the fall 2025 flu season but pushed this estimate to 2026 before ultimately pulling its biologics license application (BLA) in late May.

The FDA's request for additional efficacy data on the flu component of the vaccine underscores a broader shift in regulatory approach. Moderna has since released Phase III results showing its immunization outperformed current standards by 26.6% in preventing disease in adults aged 50 and older. Despite this data, the path forward remains unclear.

"It's a lot of moving parts, purely from a regulatory point of view," noted Myles Minter, an analyst at William Blair, highlighting the complexity of the current situation.

New Regulatory Landscape and Its Challenges

The FDA has recently made several announcements that are reshaping the approval process for new vaccines and seasonal updates. These changes include:

1. Requiring a saline placebo in clinical trials
2. Demanding efficacy data rather than just immunogenicity data
3. Implementing stricter guidelines for mRNA technology

Furthermore, the industry is grappling with the novelty of COVID-19 as a disease and the use of mRNA technology in vaccines. The current Department of Health and Human Services, under Secretary Robert F. Kennedy Jr., has been identified as potentially targeting mRNA technology, adding another layer of uncertainty.

Vinay Prasad, director of the Center for Biologics Evaluation and Research, has also played a significant role in recent decisions. He overruled FDA reviewers to restrict the label for Moderna's Spikevax and mNEXSPIKE vaccines, limiting their use to adults 65 and older and younger patients at increased risk.

Industry Response and Future Outlook

As companies navigate this new landscape, many are reevaluating their approaches:

• Novavax has paused work on its flu-COVID combo vaccine until it can find a development partner, although its adjuvant is being used in two combination vaccines by partner Sanofi.
• GeoVax is prioritizing individual shots over combination vaccines, focusing on a multi-antigen approach that aligns with current leadership preferences.
• Pfizer is in discussions with regulators after its combination shot failed to outperform previous generation flu vaccines in immunogenicity last summer.

Despite these challenges, industry experts remain cautiously optimistic. "Data is the data," Minter emphasized, suggesting that clear efficacy results in target populations should still lead to approvals.

As the pharmaceutical industry adapts to these new regulatory realities, frequent communication with drug regulators and alignment with evolving requirements will be crucial for success in bringing combination flu/COVID vaccines to market.