FDA analysis suggests J&J has not presented robust evidence for boosters

In a new analysis, the Food and Drug Administration questioned the strength of evidence that Johnson & Johnson provided in its application for booster shots. A key test used by the company was likely not sensitive enough, the agency suggested, adding that it did not have enough time to independently review much of the raw data from the trials.

The document, released before a Friday meeting of the agency’s vaccine advisers, could have significant influence on whether the 15 million Americans who have received the one-dose vaccine will be allowed to get a second shot or if they will instead be urged to get a different brand of vaccine for added protection.

The agency’s analysis follows a report released Tuesday in which Johnson & Johnson argued in favor of a booster, presenting data from a number of trials.

“A booster dose is recommended at six months or later, based on the strength of the immune responses,” the company wrote.

But Wednesday, the FDA said that the test used by the company to measure the immune response of a six-month boost — known as a psVNA assay — is not sensitive enough for the task. The agency also questioned whether the increase in immune response was as big as the data suggested.

“It is likely that the results seen are due to the low sensitivity of the psVNA assay used,” the FDA stated in its report.

The FDA saw a potential improvement in protection from a J&J booster given two months after the first shot, based on a large trial sponsored by the company.

“Although not independently confirmed by FDA from datasets, summaries of the data suggest there may be a benefit in a second dose administered approximately 2 months after the primary dose,” the agency said in its report.

The fact that the FDA had not independently confirmed key data was a departure from past briefing documents for other vaccines. The FDA said that it did not have time to vet much of Johnson & Johnson’s material before the meeting later in the week.

The agency scheduled the meeting of its outside advisers before the company had even submitted its application for a booster dose — an unusual move, some public health experts said.

“Except where noted, datasets were not submitted in sufficient time for FDA to conduct an independent review to verify the Sponsor’s analyses,” the FDA said in its report.

A spokesperson for Johnson & Johnson did not immediately respond to a request for comment.

The FDA has already authorized an additional shot of the Pfizer-BioNTech vaccine for people older than 65 or with health conditions or job exposures that put them at higher risk. Moderna has also submitted an application for a booster that will be evaluated by the FDA’s advisers Thursday. It may also win authorization, despite limited evidence that the protection provided by an initial two doses of Moderna is waning.

When Johnson & Johnson’s vaccine was authorized in February, it had several advantages over the other two. As a single shot, it was more convenient than the two-dose formulation from Moderna and Pfizer-BioNTech. It also did not have to be frozen to stay viable. But it also provided less robust protection.

A clinical trial showed that one dose of J&J had an efficacy rate of 66% against moderate to severe COVID-19 worldwide and 74 per cent in the United States. Its efficacy against either severe or critical disease was stronger, at 85 per cent worldwide.

In its application for a booster, Johnson & Johnson included the results of another large-scale trial that began in November in which they gave half their volunteers a second dose two months after the first. The other half received a placebo.

In August, the company announced that in the portion of the trial that took place in the United States, the efficacy rose to 94 per cent. But in its report, the FDA focused on the worldwide results in which the increase was more modest, rising to 75 per cent.

Against severe to critical COVID-19, two shots had an efficacy of 100 per cent. But regulators warned in the analysis posted Wednesday that there was little data from that trial on the delta variant, which now causes the vast majority of US infections.

“The small number of accrued cases confirmed to be caused by the delta variant precludes any conclusion regarding efficacy against that variant,” they wrote.