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FDA advisers back Johnson & Johnson vaccine booster

Data show second shot is safe but FDA couldn't verify studies

Colored tape on the floor guides COVID-19 vaccine recipients at a neighborhood vaccination center in Washington earlier this year.
Colored tape on the floor guides COVID-19 vaccine recipients at a neighborhood vaccination center in Washington earlier this year. (Bill Clark/CQ Roll Call)

Advisers to the Food and Drug Administration voted, 19-0, to authorize a Johnson & Johnson COVID-19 booster shot at least two months after the first dose, providing some reassurance to the 14 million Americans who received its vaccine and face a higher risk of mild cases than other vaccinated people.

The Vaccines and Related Biological Products Advisory Committee recommended the second shot after parsing the data for five hours. The panel also showed some support at its meeting Friday for allowing people to get a booster shot made by a different manufacturer than the vaccine they originally received.

FDA and Centers for Disease Control and Prevention officials said at the meeting that real-world evidence suggests the single dose shot is less effective than the Pfizer-BioNTech and Moderna vaccines, including against hospitalization. Johnson & Johnson argued two doses of its vaccine would ramp up efficacy to 94 percent, comparable to those other authorized vaccines.

The company also said its vaccine provided more durable immunity than the mRNA vaccines, but that immunity has seen a dangerous decline due to variants like delta.

The company’s studies suggested a second dose of the vaccine would boost antibody levels by 1.5-fold to 4.5-fold.

The committee found evidence suggesting declining immunity and the safety of a second shot compelling, while also critiquing major gaps in the data and FDA’s analysis.

The next step in making a booster available is for the FDA to formally issue an emergency use authorization. The agency usually follows its advisers’ recommendations. After that, independent advisers to the CDC will evaluate the FDA’s emergency use authorization, and CDC Director Rochelle Walensky will offer guidance after hearing her own advisers’ recommendations.

Limited analysis

The debate on boosters was also penned in by restrictions imposed by the FDA and the pharmaceutical company.

Johnson & Johnson recipients may potentially be getting an inferior booster because the committee was not given the opportunity to vote on the merits of boosting with one of the two mRNA vaccines, which a recent preprint study backed by the National Institutes of Health suggested would be seven to 10 times more powerful.

Center for Biologics Evaluation and Research Director Peter Marks said “it’s possible” that the FDA could authorize Moderna and Pfizer-BioNTech vaccines for the single shot group, but did not offer details.

Some panelists nearly rejected allowing a second Johnson & Johnson shot because the studies were small and the FDA faced an arbitrary deadline to complete its review, hobbling the independent verification of the company’s analysis and data that the FDA typically conducts. That practice makes the agency a “gold standard” among drug regulatory agencies around the world.

“This is still a public health imperative,” said Archana Chatterjee, dean of the Chicago Medical School. “Even though I remain concerned about the very limited number of participants in the safety and effectiveness data, I would say I’m in agreement … that this second dose, booster, whatever you call it, is necessary to boost immunity into the 90-percent range.”

Chatterjee said she nearly voted down the recommendation because of the paltry evidence from Johnson & Johnson, but evidence from the CDC on the risk of hospitalization among some Johnson & Johnson recipients changed her thinking.

The company did not submit the necessary data to the FDA until recently, said one agency official.

The FDA could not independently verify results on immunogenicity — the level of antibody levels in the blood — except in a study that looked at 17 people who got a booster shot six months after the first shot.

“Datasets for the studies were not submitted in time for FDA to conduct an independent review to verify [Johnson & Johnson’s] analyses,” said FDA medical officer Rachel Zhang, except the immunogenicity assessments of the six-month booster interval.

The agency also flagged the method Johnson & Johnson used to measure neutralizing antibody levels in some of its analyses as prone to error, and said the company may have undercounted the number of neutralizing antibodies people had in their bloodstream before a boost.

“The interpretation of this data is limited by the small sample sizes,” said FDA medical officer Timothy Brennan.

The company watched for side effects after a boost for 36 days in its most robust safety study, less than the two months typical with COVID-19 vaccines, which hampered the FDA’s analysis.

The confusion prompted tough questions from the committee.

“FDA recognized that there was intense public interest and a sense of urgency to provide a second dose,” said Doran Fink, the FDA’s deputy clinical director in the division of vaccines and related products applications. “An advisory committee meeting was scheduled to review the data available… Datasets were not submitted to FDA until just recently.”

Neither FDA official mentioned the early departures of the two top vaccinologists at the Office of Vaccines Research and Review, reportedly in protest of the speed of the booster rollout. Some former FDA drug reviewers had expressed concern that Marks’ takeover of the vaccines office would jeopardize the strength of the agency’s analysis.

Later in the meeting, Ofer Levy, director of the precision vaccines program at Boston Children’s Hospital, asked Marks how long it would require to decipher the small immunogenicity studies that were not analyzed by FDA. The agency did not provide specifics.

Marks also conceded that the FDA should have analyzed and presented more real-world data showing waning immunity.

About 33.5 million Johnson & Johnson doses have been administered around the world.

Safety data

Johnson & Johnson and the FDA also presented safety data suggesting severe side effects from the viral vector vaccine are extremely rare.

The Johnson & Johnson vaccine has had a turbulent run in the U.S. following a pause while the FDA investigated reports of thrombosis with thrombocytopenia, or blood clotting.

Public health agencies reported a decline in demand for the vaccine. The vaccine, which was easier to use than the mRNA vaccines requiring storage at very low temperatures, sat on the shelf. The FDA determined it could extend the expiration date of doses twice, and yet, hundreds of thousands of doses are at risk of being tossed out.

Johnson & Johnson said the rate of thrombosis with thrombocytopenia occurs at a rate of 2.1 cases per million doses, with an increased risk in women in their mid-thirties through their mid-sixties.

Another condition, Guillain-Barré syndrome, occurs at a rate of 7.5 cases per million doses. And capillary leak syndrome occurs at a rate of 0.2 cases per million doses.

Support for switching vaccines

The committee signaled some support for mixing and matching vaccines during a general discussion of the NIH-backed study after the vote.

Michael Kurilla, director of the division of clinical innovation at NIH’s National Center for Advancing Translational Sciences, expressed some exasperation that allowing Johnson & Johnson recipients to get a different vaccine to boost their immunity might require more nine-hour committee meetings. Kurilla suggested moving the Moderna and Johnson & Johnson products through full approval more quickly so they could be used more flexibly.

“Trying to parse it out with each particular combination? We’re going to be having VRBPAC meetings nonstop for the next several months if we do this,” he said.

But Amanda Cohn, executive secretary of the CDC’s committee of advisers, suggested that the FDA could append Johnson & Johnson’s emergency use authorization with language to allow for some flexibility.

“From a public health perspective, there is in some situations a clear need for individuals to receive a different vaccine,” Cohn said.

This flexibility would be helpful for vaccinating hard-to-reach populations, including nursing home residents, according to Melinda Wharton, an associate director at the CDC’s National Center for Immunization and Respiratory Diseases.

Even after two all-day meetings on additional shots this week, the Biden administration’s goals for booster shots remains somewhat vague, according to some committee members.

“What exactly are we trying to accomplish?” said Kurilla. “If we’re trying to drive to zero COVID, I don’t think that’s going to work.”

“We don’t want to have a wave of COVID-19 before we deploy boosters,” Marks replied. “I agree we can’t prevent every single case of COVID . . . I think there is a risk-benefit analysis here.”

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