Moderna’s Combination Vaccine Faces Uncertain Future Amid Policy Shifts
Moderna’s innovative mRNA-based vaccine, designed to provide combined protection against both influenza and COVID-19, is navigating a complex regulatory landscape that could significantly delay its approval. The vaccine, codenamed mRNA-1083, has shown promising results in Phase III clinical trials, demonstrating comparable or even superior immune responses compared to existing, separate flu and COVID-19 vaccines. However, recent policy changes within the Food and Drug Administration (FDA), driven by shifts in leadership and evolving regulatory priorities, are casting a shadow over the future of mRNA-1083 and other forthcoming vaccines.
The Phase III trial for mRNA-1083, the data of which were recently published in JAMA, involved a cohort of 8,000 participants divided into two age groups: individuals aged 50 to 64 and those over 65. Participants were randomly assigned to receive either mRNA-1083 or currently approved influenza and COVID-19 vaccines. The findings revealed that mRNA-1083 elicited a strong immune response across both age groups, with participants exhibiting comparable or higher levels of antibody-based (humoral) immunity against circulating strains of influenza and COVID-19 compared to those who received separate vaccines. Notably, the immune response to influenza strains was, on average, even higher in the mRNA-1083 group. The vaccine was also found to be safe and well-tolerated, according to the authors of the study.
These results would traditionally signal a clear path toward FDA approval. However, the regulatory environment has undergone significant changes, introducing uncertainty into the approval process. The Department of Health and Human Services (HHS) has recently mandated a comprehensive overhaul of the vaccine approval process, requiring all new vaccines to undergo placebo-controlled trials before being granted approval.
While many experimental vaccines, including the initial COVID-19 vaccines, undergo placebo testing, the scope of this new policy remains unclear. Specifically, questions arise regarding its applicability to vaccines that are compared to existing, approved vaccines, such as the combination mRNA-1083 vaccine, or to vaccines that require frequent updates to match rapidly evolving viruses like influenza and COVID-19.
Some vaccine experts have expressed concerns that these policy changes are both unnecessary and potentially unethical. Requiring placebo-controlled trials when effective vaccines already exist could leave some individuals vulnerable to infections that could be prevented through vaccination. Furthermore, the new rule could delay the availability of crucial seasonal vaccines, especially the updated COVID-19 shots designed to target emerging variants.
A significant factor that could impact the approval pathway for mRNA-1083 is the fact that no mRNA-based vaccine for influenza is currently approved. This reality could provide the FDA with the rationale to demand further placebo-controlled trials, even if the combination vaccine demonstrates superiority over existing, separate vaccines.
Additionally, the current political climate and the skepticism surrounding mRNA-based vaccines held by some officials, including Robert F. Kennedy Jr., could further complicate matters. Kennedy, who has a long history of anti-vaccination advocacy, has falsely claimed that the mRNA COVID-19 vaccines are the "deadliest vaccines ever made," despite the lack of scientific evidence to support this assertion.
Moderna has already adjusted its expectations for mRNA-1083’s approval timeline. The company stated last week that it does not anticipate the vaccine to be approved before 2026, following the FDA’s request for late-stage data demonstrating the vaccine’s effectiveness specifically against influenza. However, the evolving regulatory landscape and the prevailing political climate raise concerns about whether even this timeline is now at risk.
The combination mRNA-1083 vaccine holds the potential to streamline vaccination efforts and enhance protection against both influenza and COVID-19. Its success in clinical trials demonstrates the promise of mRNA technology in developing innovative vaccines. However, the future of this vaccine and other similar innovations depends on navigating the shifting sands of regulatory policy and overcoming the skepticism surrounding mRNA technology.
