In a series of memos last week, Center for Biologics Evaluation and Research Director Vinay Prasad outlined the FDA’s thinking on the recent limited approvals for updated COVID-19 vaccines.
Back from his 10-day hiatus, Center for Biologics Evaluation and Research Director Vinay Prasad is picking up where he left off: Shifting regulatory policy toward more stringent approval guidelines for vaccines.
In a series of memos dated Aug. 28, Prasad explains the recent FDA approvals for updated COVID-19 shots from Moderna, Novavax and Pfizer. The regulator signed off on four such vaccines last week for the upcoming respiratory virus season, but with key restrictions according to the patients’ age and risk profile for severe disease.
Regarding the Pfizer decision, Prasad noted that in reviewing the application for Comirnaty, the FDA questioned whether there is “substantial certainty of a net clinical benefit . . . to vaccinating healthy persons with this mRNA vaccine.” CBER, according to Prasad, decided that the answer to this question, “with best available information,” was no, suggesting that for this population, the benefits of the vaccine do not outweigh its harms.
Nevertheless, the regulator agreed that for at-risk patients, the risk/benefit equation came out in Comirnaty’s favor.
Prasad’s comments also put the use of immunogenicity as an outcome measure under the spotlight. Many companies use this endpoint, which measures the body’s capacity to produce antibodies against the target virus, as the basis for their regulatory submissions.
“Make no mistake,” Prasad wrote in his memo to Pfizer, “antibody titers are a surrogate endpoint.” He concedes that they “can and do” indicate clinical outcomes in certain cases, “but not all circumstances.” Concluding that a vaccine has a net clinical benefit because it increases antibody levels in patients “is not gold standard science,” Prasad stated.
The CBER director’s memos for Moderna’s mNEXSPIKE and Spikevax and Novavax’s Nuvaxovid were shorter, each just two pages in length. In all three cases, the FDA has required post-marketing commitments from the companies, which requires them to conduct additional trials to confirm the clinical benefit of their vaccines, as well as beef up their safety evidence.
According to Prasad’s memos, the three vaccines were granted approval under CBER’s “prior standard,” which was to accept “small immunogenicity studies using human sera.” Prasad argued, however, that this can only capture “numerical improvements” in the production of antibodies against the virus. “These studies lacked formal statistical prespecification and power to test a clear scientific hypothesis,” he said, claiming that companies have used such studies to justify updating strains for their vaccines, “even while there has been substantial uncertainty” that such changes are needed.
Moving forward, “CBER will demand studies roughly 5 to 10 times larger than historically accepted,” Prasad wrote.
Prasad’s memos fall in line with the broader changes that Health Secretary Robert F. Kennedy Jr. has been pushing for regarding COVID-19 vaccination. In May, Kennedy officially removed these shots from the CDC’s routine immunization guidelines for healthy children and healthy pregnant women. Then, last week, The Daily Beast reported that Kennedy and President Donald Trump could completely ban COVID-19 vaccines from the U.S. “within months.”
In a post on his Truth Social platform on Monday, Trump requested that pharma companies release data pertaining to the success of the COVID-19 “drugs” in order to “clear up this mess” at the CDC. The mess to which Trump is referring is very likely the firing of director Susan Monarez last week and the subsequent resignation of three other senior level CDC officials.
