FDA Vaccine Rules Challenged as Weak at Advisory Panel Meeting

(Bloomberg) -- U.S. vaccine advisers questioned whether safety and efficacy standards set by Food and Drug Administration officials were high enough to warrant emergency authorization of a shot.

About two dozen outside advisers to the FDA with expertise in infectious diseases met Thursday to weigh in on agency standards that require a vaccine to work in at least 50% of people and for drugmakers to collect two months of safety data on at least half of clinical trial volunteers.

“They haven’t gone far enough” in terms of safety, said Hayley Altman-Gans, a panel member and pediatrics professor at Stanford University Medical Center.

Many panel members and outside researchers who commented during the hearing worried that if a vaccine is rushed out that later turns out to have safety problems or to be less effective than promised, it could backfire in a big way, undermining public confidence in Covid-19 vaccines for years to come.

Archana Chatterjee, advisory panel member and dean of Chicago Medical School, said the public has a lot of concern about safety. Meanwhile, she added, “What we’re being asked to do is to build this plane as we fly it.”

Several panel members expressed concern that the two-month safety follow-up the FDA is calling for before a vaccine gets an emergency authorization is simply not enough. In addition to safety, it means that doctors won’t know whether a vaccine’s efficacy could fade after just a few months.

Panel member Amanda Cohn, who is chief medical officer at the National Center for Immunization and Respiratory Diseases, worried that the efficacy of vaccines that just meet the 50% threshold after two months may see reduced effectiveness a few months later if the shot doesn’t offer a long period of protection.

“Very rarely do we look at [vaccine efficacy] so shortly after completing a series,” according to Cohn, whose organization is part of the Centers for Disease Control and Prevention.

Design Flaws

The advisers weren’t alone in questioning the standards. Diana Zuckerman of the National Center for Health Research told the committee the vaccine trials “have serious design flaws.”

The two-month follow up the FDA has asked for is too short to establish how long a vaccine will work, and the trials are too geared to preventing mild infections, and may not show whether they prevent severe infections and hospitalizations, she said.

Longer follow=up may be especially important because some of the first vaccines, including messenger RNA vaccines from Pfizer Inc. and Moderna Inc., are based on new technologies that have never been used in an approved product.

The debate over the rigor of the FDA guidelines was one of two main issues debated before the committee, which heard comments from regulators, drugmakers and the public. The second questioned whether trial participants on a placebo should be advised when a vaccine is deemed to be safe and effective.

No Advising

Drugmakers developing Covid-19 vaccines shouldn’t advise trial participants they’re getting a placebo, even if the vaccine is preliminarily found to be safe and effective, a federal official said Thursday.

Speaking before the FDA’s vaccine advisory committee, Doran Fink, a deputy director of the agency, said drugmakers that get emergency authorization based on preliminary efficacy data and two months of safety information should seek full agency approval as soon as possible.

To meet the more-stringent approval criteria for full approval, he said, it requires that developers not reveal who is getting a placebo so they can generate more robust data on how well the vaccine works and how long it lasts, though there is a risk of those on a placebo getting ill.

The advisory panel met to discuss what data regulators should seek before and after authorizing a vaccine. No specific product was addressed during the session.

Pfizer, J&J

In comments to the agency ahead of the advisory meeting, Pfizer and Johnson & Johnson both raised questions about the ethics of leaving participants in the trial on placebos when their vaccine has been shown to work.

“If Pfizer’s vaccine is granted Emergency Use Authorization, we would propose to amend our ongoing study to allow cross-over of eligible placebo subjects to the active vaccine arm if they wish to do so at any time,” Peter Honig, senior vice president of global regulatory affairs at Pfizer, wrote in the comments.

Meanwhile, FDA’s Fink said there is discussion about the possibility of comparing vaccines under development to those that have already received emergency authorization if maintaining a placebo group in trials isn’t possible.

Globally, there are about 200 experimental vaccines in development, according to the World Health Organization. Of those, 44 have entered human studies.

The Vanguard

In the U.S., experimental shots from Pfizer in partnership with BioNTech SE, and J&J are among the vanguard, having entered into large, late-stage studies that could read out data before year-end.

Pfizer aims to be the first company to gain FDA authorization for a Covid-19 vaccine. J&J is a few months behind them and said in comments before the meeting it is “evaluating a number of measures aimed at maintaining Phase 3 trial retention, should a COVID-19 vaccine become available before our trial is complete.”

Pfizer Chief Executive Officer Albert Bourla said last week that the drug giant could seek emergency-use approval by late November if the shot is effective in a large late-stage trial.

The FDA often seeks recommendations on approval or rejection of new drugs and devices from outside advisers, and has said such a panel will also meet on specific Covid-19 vaccines once applications for emergency use are received.

©2020 Bloomberg L.P.