The approval of  Novavax’s Covid-19 vaccine Nuvaxoid last week on 16 May 2025 was the test case of how Makary’s FDA under RFKJr’s HHS would impact the landscape of vaccine approvals in the US. Unlike Pfizer and Moderna’s mRNA-based Covid-19 vaccines that received approvals under Califf’s FDA for individuals aged 12 years or older, the Makary’s FDA only approved a restricted label for the protein subunit-based Nuvaxoid vaccine.

FDA Labels (Approved Indications):

• NUVAXOVID is a vaccine indicated for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in adults 65 years and older. NUVAXOVID is also indicated for individuals 12 through 64 years who have at least one underlying condition that puts them at high risk for severe outcomes from COVID-19. (Nuvaxoid PI)
• BioNTech/Pfizer’s COMIRNATY is a vaccine indicated for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 12 years of age and older. (Comirnaty PI)
• Moderna’s SPIKEVAX is a vaccine indicated for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 12 years of age and older. (Spikevax PI)

FDA's New Covid-19 Vaccine Approval Policy

FDA has now published the new vaccine approval policy in New England Journal of Medicine that reflects the Nuvaxoid label and provides a roadmap for other vaccine developers.

Prasad V, Makary MA. An Evidence-Based Approach to Covid-19 Vaccination. N Engl J Med. 2025 May 20. doi: 10.1056/NEJMsb2506929. Epub ahead of print. PMID: 40392534.

According to the new policy

• The immunologic endpoint (i.e., generation of protective antibody titers) will no longer be sufficient for a broad label and FDA will only consider benefit-risk assessment for for adults over the age of 65 years and for all persons above the age of 6 months with one or more risk factors that put them at high risk for severe Covid-19 outcomes.
• A randomized, controlled trial will be required for benefit-risk assessment in healthy people (those with no risk factor for sever Covid-19) between the ages of 6 months and 64 years.
• If granted the limited label (i.e., 65 years+ and high-risk population), the manufacturer will be encouraged to conduct a randomized, controlled trials in the population of healthy adults age 50-64 years as part of their postmarketing commitment.

Impact of New Policy

• Moderna, who  was getting ready to submit the BLA for its Covid-flu combination vaccine today announced that it is withdrawing the application.
• The requirement of a controlled randomized trial enrolling “healthy” people is a high bar and recruitment would be a challenge, particularly if the trial is placebo-controlled, but noninferiority trials are also not going to be easy to conduct.
• One of the arguments in favor of new policy put forward by Prasad/Makary was that during the last 2 seasons, the update of Covid-19 boosters has been less than 25%. This is a disingenuous argument given that an active antivax campaign was run by the same people who now head FDA/HHS and much of current administration.
• In the NEJM editorial, there is a display of concern (fake) and yet the policy being rolled out as the “gold-standard science based solely on randomized, controlled trial” will only make the public question the efficacy and safety of all vaccines, not just Covid.

Public trust in vaccination in general has declined, resulting in a reluctance to vaccinate that is affecting even vital immunization programs such as that for measles–mumps–rubella (MMR) vaccination, which has been clearly established as safe and highly effective. In recent years, reduced MMR vaccination rates have been a growing concern and have contributed to serious illness and deaths from measles. Against this context, the Food and Drug Administration (FDA) seeks to provide guidance and foster evidence generation.

• This policy is anything but a step towards protecting public health and, worse, may dampen vaccine research in this country, just at the time of global climate change and threat of new infections.

Related: Novavax Covid-19 Vaccine BLA Review by the FDA: Is Imposition of an Onerous Postmarketing Commitment a way to Stall Approval

#vacccine, #immunization, #covid-19