FDA Panel Rejects Pfizer Proposal For Universal Covid Booster Shots

Pfizer had been pushing universal booster shots hard, raising questions about to what degree its motives were financial rather than medical.

The panel's recommendation still means that tens of millions should get boosters, including seniors, those with autoimmune conditions and health workers, first responders or others with jobs that put them at risk. JL  

Sharon LaFraniere and Noah Weiland report in the New York Times:

A key advisory panel to the FDA overwhelmingly rejected recommending Pfizer booster shots for most recipients of the company’s coronavirus vaccine, endorsing them only for people who are 65 or older or at high risk of severe Covid-19. Health workers, emergency responders and others at special risk should also be eligible for the shots. Committee members appeared dismissive of the argument that the general population needed booster shots.

A key advisory panel to the Food and Drug Administration overwhelmingly rejected recommending Pfizer booster shots for most recipients of the company’s coronavirus vaccine, instead endorsing them only for people who are 65 or older or at high risk of severe Covid-19, and received their second dose at least six months ago.

The vote — the first on boosters in the United States — was a blow to the Biden administration’s strategy to make extra shots available to most fully vaccinated adults in the United States eight months after they received a second dose. The broader rollout was to start next week.

Committee members appeared dismissive of the argument that the general population needed booster shots, saying the data from Pfizer and elsewhere still seemed to show two shots protected against severe disease or hospitalization and did not prove a third shot would stem the spread of infection. Some also criticized a lack of data that an additional injection would be safe for younger people.

“It’s unclear that everyone needs to be boosted, other than a subset of the population that clearly would be at high risk for serious disease,” said Dr. Michael G. Kurilla, a committee member and official at the National Institutes of Health.

But the panel’s final recommendation left some room for the White House to argue that the core of its booster strategy remained intact. Depending on how “at high risk” is defined, tens of millions of Americans could conceivably wind up eligible for additional shots of the Pfizer vaccine.

The committee of largely outside experts voted 16 to 2 against a Pfizer booster for people 16 and older after a tense daylong public discussion that put divisions in the agency and the administration on public display. Officials from the Centers for Disease Control and Prevention and the National Institutes of Health joined infectious disease experts and doctors in voting against additional shots for such a broad swath of the population.

Dr. Paul A. Offit, a committee member and the director of the Vaccine Education Center at Children’s Hospital of Philadelphia, questioned whether extra shots would do much at all to change the arc of the pandemic. “We all agree that if we really want to impact this pandemic, we need to vaccinate the unvaccinated,” he said.

But the panel unanimously embraced a fallback position to limit additional shots to older adults and others at high risk of severe Covid illness. Then, after an informal poll pushed by a senior F.D.A. official, committee members specified that health care workers, emergency responders and others whose jobs put them at special risk should also be eligible for the booster shots. The official — Dr. Peter Marks, who oversees the F.D.A.’s vaccine division — said the at-risk group would also include teachers.

Aides in the Biden administration noted that under the White House’s plan to offer booster shots eight months after the second injections, many in that same group would have been first in line because they were vaccinated earliest.

The F.D.A. has the final word on vaccine approvals, and while it is not obliged to follow the committee’s recommendations, it typically does. The agency is likely to issue a decision by early next week.

An advisory committee of the C.D.C. is scheduled to meet Wednesday and Thursday to discuss booster shots before that agency, which sets vaccine policy, issues recommendations on who exactly should receive them.

In a statement about Friday’s vote, Kathrin U. Jansen, senior vice president and head of vaccine research and development at Pfizer, said, “We thank the committee for their thoughtful review of the data and will work with the F.D.A. following today’s meeting to address the committee’s questions, as we continue to believe in the benefits of a booster dose for a broader population.”

Those who have criticized the administration’s booster strategy as overly broad or premature said the advisory committee acted as a necessary check on Friday.

The meeting “put the F.D.A. back in the driver’s seat,” said Dr. Luciana Borio, a former acting chief scientist at the agency. The expert panel, she said, “was allowed to maintain its scientific independence. It understood there were significant limitations with the data presented and that the F.D.A. needs to review the data carefully before making a decision.

The committee’s rejection of boosters for everyone over 16 was the latest setback for the plan that Mr. Biden announced a month ago. The announcement prompted weeks of criticism from public health experts, who accused the administration of trying to set booster policy before F.D.A. and C.D.C. clearance. Regulators were forced to try to gather and analyze data at top speed, aiming to meet a deadline of next week that they had not set.

Two weeks after Mr. Biden’s announcement, leaders of the F.D.A. and the C.D.C. told the White House that it would be impossible to authorize booster shots for recipients of the Moderna vaccine that soon.

Then, in a remarkable public display of internal dissension, two F.D.A. scientists wrote a medical journal article this week arguing that there was no credible evidence yet in support of boosters for the general population. Those officials, who are leaving the agency this fall, joined outside experts at the Friday meeting in casting doubt on whether Pfizer’s request should be approved.

Dr. Marks, their boss, also addressed the committee, noting that many well-known vaccines required booster shots. He also suggested that the committee consider the importance not just of preventing severe disease but also of curbing the spread of infection.

The panel listened to hours of contradictory presentations by officials from Pfizer, the C.D.C., the Israeli government and independent experts about the waning effectiveness of Pfizer and other vaccines over time.

Dr. Sara Oliver of the C.D.C. presented data showing that vaccines continue to strongly protect against severe forms of Covid-19 in the United States, even in people 75 and older.

Jonathan Sterne, a professor of medical statistics and epidemiology in Britain, said he had analyzed 76 different studies on the vaccines’ real-world effectiveness and found that multiple factors could skew the results, including how many unvaccinated people in a study had natural immunity from prior infection. He also warned against drawing conclusions from short-term results from booster shots; data from Israel, for example, only included a follow-up period of several weeks for older adults.

Israeli experts made a different argument, telling the committee that they believed third Pfizer shots helped dampen a fourth wave of transmission as the Delta variant swept the nation this summer. The Israeli government, which has relied almost entirely on the Pfizer vaccine, began offering booster shots in late July, starting with the older adults.

Dr. Sharon Alroy-Preis, Israel’s head of public health services, said the summer’s rise in the number of hospitalized patients who had been fully vaccinated with Pfizer’s vaccine was “scary.” She said 60 percent of severely or critically ill patients and 45 percent of those who died during what she called the fourth surge had received two injections of Pfizer’s vaccine.

After offering boosters to the general population, she said, Israel was now averaging about half as many severe or critically ill patients as anticipated. She said boosters not only helped curb the spread of infection, but also “actually saved lives.”

Dr. William C. Gruber, a senior Pfizer vice president in charge of vaccine development, suggested that if the United States does not follow Israel’s lead, it could face more than five million more infections a year among people who received their second dose 10 months earlier, compared to those who got the second shot five months earlier.

“Israel could portend the U.S. Covid-19 future, and soon,” he said.

He said Pfizer’s data showed that a third shot elicited a robust antibody immune response that equaled or greatly exceeded the response after the second dose. Data also show, he argued, that breakthrough infections among vaccinated Americans are linked more to the ebbing power of the vaccine over time than to the Delta variant.

But committee members and some government officials appeared deeply skeptical. Dr. Philip Krause, one of the F.D.A. vaccine experts who wrote the medical journal review, criticized Pfizer’s presentation of data that had not been peer-reviewed or evaluated by the F.D.A., arguing that problems in the modeling in a study underpinning the company’s case understated the vaccine’s efficacy.

Dr. Oliver, the C.D.C. official, questioned attempts to draw a parallel between the United States and Israel, noting that Israel has only nine million residents and is less diverse than the United States. Notably, she also said that Israel defines a severe case of Covid-19 more broadly than the United States does, which might help explain why Israel reports more serious breakthrough infections among its vaccinated residents.

Another C.D.C. official, Dr. Amanda Cohn, asked Israeli officials why the spread of the virus there had recently intensified, despite a broad rollout of boosters. Dr. Alroy-Preis said that the Jewish holidays, along with the start of the school year, had contributed to what she suggested would be a temporary surge in cases.

Committee members also said they were concerned about a paucity of safety data in younger recipients of a booster dose, since studies have shown a higher risk of myocarditis, an inflammation of the heart muscle, in young men who received Pfizer-BioNTech’s vaccine. Several asked whether it would be better to wait for a booster vaccine devised specifically to fend off the Delta variant of the virus.

One study apparently came too late for the discussion, underscoring the rapid flurry of changing data on vaccine potency. Released by the C.D.C. hours before the committee’s vote, it found that the Pfizer vaccine’s level of protection against coronavirus hospitalizations dropped significantly four months after the second shot.

The study found that two weeks to four months after recipients got their second dose, the Pfizer vaccine was 91 percent effective in preventing hospitalization. After 120 days, though, its effectiveness fell to 77 percent. Moderna’s vaccine showed no comparable decrease in protection over the same time frame. The vaccinated patients in the study tended to be older; the Pfizer cohort had a median age of 68.