木瓜直播

Will an suggest that the agency go slow on COVID-19 vaccine reviews? Or will members recommend putting the pedal to the metal?

Those are the questions to which everyone eagerly anticipates answers by day's end, as the FDA's Vaccines and Related Biological Products Advisory Committee (VRBPAC) discusses... well, it's not known exactly what, outside the agency.

Unlike most so-called FDA AdComms, this one doesn't come with a list of discussion and/or voting questions posted ahead of time. In this case, the agency said VRBPAC "will meet in open session, to discuss, in general, the development, authorization and/or licensure of vaccines to prevent COVID-19. No specific application will be discussed at this meeting."

A further states that the committee will discuss studies needed to evaluate safety and efficacy, "including in special populations" such as children and pregnant women, "and to further evaluate the immunogenicity and duration of effectiveness of these vaccines." Such studies could be required prior to formal approval and/or afterward.

"Furthermore, the committee will be asked to discuss what would be necessary for active safety follow up in order to permit an ongoing assessment of the benefits and risks of a COVID-19 vaccine following issuance of an EUA," or emergency use authorization, the briefing document said.

However, one bit of news was included in the briefing document: a promise to hold additional VRBPAC meetings before issuing an EUA for each and every vaccine candidate.

"This discussion will be specific to the particular vaccine that is the subject of the EUA request and will be separate from, and in addition to, any general discussion by the VRBPAC regarding the development, authorization and/or licensure of vaccines to prevent COVID-19."

In June, the FDA had for COVID-19 vaccines. That was updated recently, in off-the-record conversations with individual developers, the FDA said in the briefing document. "For example, FDA has explained that sponsors should submit data from at least one well-designed Phase 3 clinical trial to support a determination by FDA that the investigational vaccine's benefits outweigh its risks. FDA also has provided detailed advice to sponsors regarding the clinical safety data and manufacturing information that should be included in an EUA request for a COVID-19 vaccine."

The agency did release a summary of the advice provided to sponsors (an appendix in the briefing document). It said, for example, that placebo-controlled trials should demonstrate vaccine efficacy of at least 50%, with 30% as the lower bound for "the appropriately alpha-adjusted confidence interval."

As has been reported previously, the agency also demands median follow-up of at least 2 months for adverse events, including COVID-19 cases "occurring during the timeframe when adaptive (rather than innate) and memory immune responses to the vaccine would be responsible for a protective effect."

Sponsors seeking EUA should also obtain enough data to show that vaccine-induced enhanced respiratory disease (ERD) is not a concern, the FDA said. To determine this statistically, at least five patients in the placebo group must develop severe COVID-19, the agency said, "to assess whether the... split between vaccine vs. placebo groups supports a favorable benefit-risk profile or conversely raises a concern about ERD."

Other requirements generally appeared typical for novel vaccines.

The two front-runners in the U.S. -- the Pfizer/BioNTech collaboration and Moderna -- have both set late November as likely targets for submitting EUA applications. AstraZeneca's phase III trial in the U.S. remains on hold after a small number of severe adverse events turned up; and a variety of other vaccines are further back in the pipeline.

Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, is expected to be part of the team that will review EUA requests. He has said he expects the first to be OK'd by the end of this year.

Comment