FDA VRBPAC Vote Avoids Mass Booster Vaccine Scenario but Approves for Elderly, At Risk, & Immunocompromised on Weak Moderna Evidence
Moderna sent a rosy message to investors that the U.S. Food and Drug Administration (FDA) Advisory Committee unanimously voted in support of Emergency Use Authorization for a booster dose of the company’s mRNA-based vaccine called mRNA-1273 for COVID-19. However, even though the company submitted limited data, the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) voted 19-9 that the overall benefits of the mRNA-1273 vaccine-based booster dose outweighs any prospective risks in population cohorts including those age 65 and up as well as younger people with high-risk medical conditions and those in cohorts deemed at risk due to occupation. What Moderna didn’t tout was that given the lack of a benefit and risk assessment, VRBPAC was not keen on recommending the greenlight of a vast mass booster campaign for all adults. This of course limits the number of vaccines the company can sell in America. The takeaway is that VRBPAC becomes much more discriminating in terms of who should receive a booster while some on the committee wondered aloud about the sponsor’s “thin” submission package. Moderna did inform investors that given the positive vote for the booster at the 50 ug level—assuming subsequent approval—could lead to an additional 1 billion doses available for distribution in 2022—of course this translates into significant revenue.
The company noted in its press release that VRBPAC recommended that the FDA grant an EUA for the booster dose of mRNA-1273 at the 50 ug dose level for the following:
People aged 65-up
People 18 to 64 who are at a high risk of severe COVID-19 complications or severe illness
The vote was unanimous in that all 19 VRBPAC members recommended the EUA under the above conditions. They recommended that the booster dose be administered at least six months after completion of the primary series.
Thin’ Evidence
Moderna shared that the VRBPAC recommendation was based on scientific evidence including analyzed data from a Phase 2 clinical study (P201) investigating mRNA-1273 booster dose at the 50-µg dose level boosting naturalizing titers significantly above the Phase 3 benchmark. They reported that after a booster dose, a comparable level of neutralizing titers was observed across age groups but particularly noticeable among those 65 and above. They reported that the safety profile for the booster was comparable for dose 2 of mRNA-1273.
Not all were fully impressed with the data. Molly Walker writing for MedPage Today reported recently that while there were no safety concerns the recent Moderna Phase 2 study yielded a “small sample size” and “no efficacy data.”
Of the 149 adults receiving the two-dose regimen, FDA staff went on the record “Immunobridging analyses against the D614G strain met with the pre-specified success criteria for the [geometric mean titers] ration.” Moreover, the staff noted that in association to seroresponse rates post the booster jab “the pre-specified success criteria was not.”
MedPage Today’s Ms. Walker reported that Patrick Moore, MD with the University of Pittsburgh Cancer Institute shared his concern with the “poor quality data submitted by the sponsor. He was quoted “I’ve got real issues with this vote…[it’s] more of a gut feeling rather than truly serious data,” and declared “I think it’s very important that companies coming to VRBPAC…really take seriously that we need to see good, solid data, and it needs to be explained well.”
Non-Binding Recommendation
Advisory committees to the FDA, such as VRBPAC provide non-binding recommendations. This means the FDA takes the recommendation into consideration while they prepare to make a final decision on authorization of the booster. Once the FDA made its decision, the U.S. Centers for Disease Control, and the Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) met to discuss a recommendation for the use of COVID-19 boosters.
Separate Approval in August
Moderna reported in their recent press release that on August 13, the FDA approved an update to the EUA for mRNA-1273 to include a third dose at the 100 ug dose level for immunocompromised people aged 18 years and up in the United States who have undergone solid organ transplantation, or who are diagnosed with conditions that are considered to have an equivalent level of immunocompromise.