FDA advisers recommend Pfizer-BioNTech coronavirus vaccine; agency action expected soon

The thumbs' up from the FDA's vaccine advisory committee was the culmination of an all-day meeting during which the panel heard presentations on the safety and effectiveness of the vaccine, including plans to monitor its longer-term safety.

The key moment came at the end of the meeting, just after 5:30 p.m. Eastern, when the agency asked its independent advisers: "Based on the totality of scientific evidence available, do the benefits of the Pfizer-BioNTech COVID-19 Vaccine outweigh its risks for use in individuals 16 years of age and older?"

The committee voted yes, 17 in favor, four against and one abstained. Panel members did not have an opportunity to explain their votes, but at least two dissenters objected to inclusion of 16- and 17-year-olds, given the low risk of severe disease in that age group and how few had participated.

"My 'no' vote was because of the inclusion of 16- 17-year-olds," said David Kim, director of the division of Vaccines in the Office of Infectious Disease and HIV/AIDS Policy. "I would have voted 'yes' most enthusiastically had the language been '. . . 18 years of age and older.' "

Panel member Paul Offit, a pediatrician and vaccine expert at the Children's Hospital of Philadelphia, vehemently that argument.

"Kids in our hospital have had cardiac anomalies," he said. "We have clear evidence of benefit, and all we have on the other side is theoretical risk."

If as expected, the FDA follows quickly with an emergency authorization, the shots will start being moved to the states within 24 hours, according to officials at Operation Warp Speed, the Trump administration's effort to accelerate the development and delivery of vaccines. Inoculations could begin early next week.

After the FDA authorization, an advisory committee to the Centers for Disease Control and Prevention will vote on whether to recommend the vaccine and for which groups. First in line to be inoculated are health care personnel and residents and staff of long-term care facilities, according to previous recommendations from the CDC panel. But states will have the final say on who gets the first shots and where they are administered. Those considerations are complicated by extreme logistics challenges, including the sub-Antarctic storage temperatures the vaccine requires.

Kathrin Jansen, Pfizer's head of vaccine research and development, told the panel that "with the high efficacy and good safety profile shown for our vaccine, and the pandemic essentially out of control, vaccine introduction is an urgent need,"

During the meeting, committee members pressed the FDA on the safety of the vaccine, including raising questions about the allergic reactions that a new issue that cropped up on Wednesday when British regulators ordered hospitals to avoid giving the shots to people who have a history of "significant" allergic reactions. That directive came after two health care workers had adverse reactions after receiving the first dose of the vaccine, which British regulators authorized last week. British authorities said both workers have a history of serious allergies.

Susan Wollersheim, a medical officer in the FDA's Office of Vaccines Research and Review, said the FDA has asked Pfizer to monitor vaccine recipients for "anaphylactic reactions" as a potential risk following the British reports.

Much remains unknown about the cases in the United Kingdom, and experts said more data was urgently needed. A specific study could be done to see if the vaccine carried risk to people with severe allergies.

"There are tens of millions of people in this country that carry EpiPens because they have peanut allergies and egg allergies. They are going to believe that they can't get this vaccine. That is a lot of people," Offit said.

In its review, the FDA found a slightly higher number of adverse events - "potentially representing allergic reactions" - in the group that received the vaccine, compared with those who got the placebo. There were 137 "hypersensitivity-related" reactions to the vaccine, compared with 111 such events in the placebo group. But there were no cases of anaphylactic reactions in the trial.

Pregnant women have been excluded from coronavirus vaccine trials, but FDA's limited data doesn't suggest a specific risk to pregnant women or a fetus. Doran Fink, deputy director of the FDA's Division of Vaccines and Related Products Applications, said the agency is expecting later this month a developmental and reproductive toxicity study in animals that could help elucidate any risks, but will likely allow pregnant women and their doctors to decide whether or not to take the vaccine.

An authorization for Pfizer-BioNTech is the first of what health experts hope will be several vaccines to cross the finish line. Next to be considered is Moderna's vaccine. The FDA will release its assessment of that vaccine on Tuesday. If it gets favorable evaluations are favorable, as expected, the FDA is likely to authorize that vaccine within days. Between the two vaccines, government officials project having 40 million doses by the end of the year - enough to fully vaccinate 20 million people with the two-shot regimen.

Canada's health regulator on Wednesday approved Pfizer's coronavirus vaccine, days ahead of possible approval in the United States. Canadian officials expect to administer them within days. Britain began vaccinations on Tuesday, after authorizing the shots last week. While some have wondered whether the FDA could have acted more quickly, Fink said the agency has been working nonstop to review the companies' data.

"The American public demands and deserves a rigorous, comprehensive and independent review of the data," Fink said. "That is what FDA physicians and scientists, all of us career public health servants, have been doing over days, nights, weekends and, yes, over the Thanksgiving holiday. This is in addition to months of review work already completed."

Besides Canada and Britain, Saudi Arabia and Bahrain also have cleared the vaccine.

There was extensive debate over how to handle the difficult issue of when to give participants who received a placebo access to the vaccine. Some participants have called for it, but the FDA has expressed concerns that "unblinding" could hurt efforts to collect longer-term safety data.

Pfizer officials on Thursday proposed to FDA that participants in the placebo group be eligible to receive the vaccine when they become eligible due to age or other risk factors if they were not in the trial. Eligibility would be determined by local and national guidelines.

In preparation for the meeting, the FDA on Tuesday published a 53-page evaluation saying the vaccine appears to meet the standards it laid out in recent months for emergency authorization. The agency has said a vaccine must be at least 50% effective; its own scientists confirmed Pfizer's assessment that the vaccine regimen was 95% effective at preventing covid-19 in a large clinical trial.

On safety, the FDA found that the vaccine has "a favorable safety profile, with no specific safety concerns identified that would preclude issuance of an [emergency authorization]." The vaccine caused several side effects, including sore arms, fatigue, headaches, muscle pain and chills, but they typically disappeared after a day or two. Pfizer provided the agency with a median of two months of follow-up on 38,000 participants in the trial.

The one surprise in the Tuesday report was that the first shot in the two-dose regimen was 52% protective against covid-19 in the three weeks between the two shots. But the FDA noted that there wasn't enough data to draw firm conclusions about the efficacy of a single shot. Government officials have said they plan to hold back supplies for the second shots, which must be given three weeks later, to ensure sufficient supply of the shot that provides people get complete protection. But the signal of early protection from a single dose has led some to suggest that may not be the best way to use limited doses in the midst of amid surging cases.

University of Michigan epidemiologist Arnold Monto is temporary chairman of the 24-person panel, whose official name is the Vaccines and Related Biological Products Advisory Committee, which also includes a consumer representative and a nonvoting member who represents the pharmaceutical industry.

The independent panel of almost 24 members, includes experts on immunology, virology and infectious diseases. They Other Members include HIV researcher James Hildreth, dean of Nashville's Meharry Medical College, one of the nation's few historically black medical schools, and Paul Offit, director of the Vaccine Education Center at the Children's Hospital of Philadelphia and co-developer of a rotavirus vaccine. The panel, whose official name is the Vaccines and Related Biological Products Advisory Committee, also includes a consumer representative and a nonvoting member who represents the pharmaceutical industry.

During the portion of the FDA's advisory committee meeting for the general public, some people expressed concerns about the authorization of a vaccine that was so rapidly developed and reviewed. But Evan Fein told the panel he was a clinical trial participant at New York University and strongly urged quick action.

He said he is certain he got the vaccine last summer - not a placebo - because he had fatigue, fever and muscle aches after the second shot. But he said there were no longer-term side effects.

He said it would be "immoral and unethical" to not authorize the vaccine.