Advisory committee meeting reflected internal tensions among FDA staff on need for boosters and adequacy of the data; mRNA vaccine Comirnaty should be authorized for a third dose in populations at high risk for severe disease or exposure, panel says after overwhelmingly rejecting Pfizer's bid for booster approval in the 16-and-older population. 

If regulators agree with Pfizer’s conclusions – and briefing documents suggest that’s a big if – about real-world studies showing Comirnaty’s effectiveness waning over time, thereby justifying the need for a booster dose, it could be part of a historical moment for FDA’s use of RWE.

Lack of reference standards inhibits ability to make comparisons between products or set caps for total vector genome dose or total capsid dose, advisory committee says; panelists suggest other approaches to prevent and mitigate toxicities, including running longer-term animal studies and investigating the efficacy of immunosuppression prophylaxis and treatment strategies.

US FDA showed some regulatory flexibility by relying on longer-term follow-up from Merck’s original single-arm trial, rather than additional confirmatory studies, to retain the first-line claim, but it narrowed the target population to those with the greatest unmet need; Keytruda indication was one of six 'dangling' accelerated approvals re-examined by Oncologic Drugs Advisory Committee in April.

FDA seeks advice on screening patients potentially at higher risk for liver and other injuries, strategies to implement before or after gene therapy administration to head off or mitigate potential adverse events, and whether upper limits should be set for the total vector genome dose and total capsid dose.

For males 16-17 years old, excess cases of myocarditis/pericarditis from Comirnaty would exceed COVID-19 hospitalizations and deaths under ‘worst case’ scenario modeled by US FDA; agency nevertheless deemed approval warranted in this subpopulation, citing prevention of nonhospitalized COVID cases and public health benefits from vaccination.