FDA REVIEW: ONE-DOSE VACCINE EFFECTIVE AND SAFE

Johnson & Johnson shot shows strong protection against severe illness

A third coronavirus vaccine could soon be available in the United States, a one-shot regimen made by pharmaceutical giant Johnson & Johnson that proved safe and effective in a clinical trial and completely protective against hospitalizations and deaths, according to a Food and Drug Administration review released Wednesday.

The document, posted in advance of an all-day meeting of FDA advisers Friday, sets the stage for a vaccine to be authorized as soon as this weekend. As the threat of virus variants continues to swirl, the prospect of another vaccine that could accelerate immunization efforts and prevent more variants from emerging offers hope in the middle of a pandemic that has killed more than a half-million people in the United States.

Public health officials have eagerly awaited the arrival of the Johnson & Johnson vaccine because it is easier to store and administer and could streamline the logistics of a complicated mass vaccination campaign. But supply will continue to limit the nation’s vaccination efforts in the near term, with the full impact of the Johnson & Johnson vaccine not expected until April as manufac

turing scales up. If the vaccine is authorized this weekend, federal officials predicted that 3 million to 4 million doses could be allocated next week, with an additional 20 million expected in March.

But the FDA review also hinted that a formidable messaging challenge may lie ahead. After the spectacular and relatively straightforward 90-plus percent effectiveness of the first two coronavirus vaccines that were authorized, the Johnson & Johnson results are more nuanced.

Johnson & Johnson’s oneshot vaccine was tested during a more complicated phase of the pandemic, when a variant capable of slipping by some immunity had emerged. It was more than 80 percent effective at preventing severe illness, including in areas of the world where concerning variants are circulating, but only 66 percent protective overall when moderate cases were included.

Experts say people should not insist on getting vaccines with higher efficacy rates, considering that a joint vaccine from pharmaceutical giant Pfizer and German biotech firm BioNTech, and one from biotech company Moderna went through clinical trials earlier, before certain variants emerged. They fear the logistical advantages of Johnson & Johnson’s vaccine could be lost if people decide to defer vaccination until they can access a particular shot. Vaccines that transform the virus from a potentially fatal disease into a nuisance illness could end the pandemic, unless they aren’t widely adopted.

“We know this vaccine prevents 85 percent of the severe disease . . . . It was 100 percent effective in preventing hospitalization and deaths, and that’s really what’s important,” said Nancy Bennett, a professor of medicine and public health sciences at the University of Rochester School of Medicine and Dentistry. “Those facts are the most important thing to recognize.”

The FDA scientists found that the “known benefits” of the vaccine included reducing the risk of symptomatic and severe cases of the disease caused by the virus, COVID-19, at least two weeks after vaccination. The review found vaccine efficacy against severe COVID-19 “was similarly high across the United States, South Africa, and Brazil.”

People working on the logistics of vaccination see clear benefits from the Johnson & Johnson vaccine because it can be stored in a refrigerator for at least three months, making it simpler to use than other vaccines that must be kept frozen. And because it is a single shot, it does not require a follow-up visit for a booster shot.

The vaccine’s efficacy rate was lower — 42 percent — in preventing moderate to severe illness in a subgroup of adults older than 60 who had medical risk factors. But regulators noted that the statistical significance of that finding was uncertain, and no deaths or cases requiring medical intervention were reported a month after those older adults received vaccines. Overall, there were seven deaths in the trial, all in the group that received a placebo.

David Benkeser, a biostatistician at Emory University’s Rollins School of Public Health, said that the lower efficacy in some older study participants warranted additional study but wasn’t yet a huge concern. He noted that the lower efficacy seemed to be driven by older adults with diabetes, and it would be important to check whether their immune responses to the vaccine were lower.

“There’s a chance that this is a bit of bad luck — if you cut the data up many ways, you are bound to find some puzzling results,” Benkeser said in an email. “For now, the news is overall very positive.”

Still, the lower efficacy among higher-risk older adults could be a topic of discussion when outside experts meet Friday to recommend whether the FDA should authorize the shot. If the regulatory deliberations follow the path of the previous two authorized coronavirus vaccines, a decision could come this weekend.

The FDA advisory committee will consider the Johnson & Johnson vaccine at a “very tenuous time,” said Nahid Bhadelia, an infectious-disease doctor at Boston Medical Center. “Nobody knows how to feel.” While hospitalizations and deaths related to COVID-19 are declining, there are concerns that variants could spoil the improving picture.

The Johnson & Johnson results highlight the challenge variants pose to all of the vaccines: The large, international trial found the vaccine was 72 percent effective at preventing cases of moderate to severe COVID-19 in the United States, where variants of concern have only recently begun to be detected. In South Africa, where a variant capable of evading some parts of immunity became dominant late last year, it was 64 percent effective against moderate to severe illness.

That drop-off is smaller than has been seen for some other vaccines. The vaccine developed by Novavax was nearly 90 percent effective in a British trial, but that protection fell to about 50 percent in South Africa. The vaccine developed by AstraZeneca and the University of Oxford, which was estimated to be 76 percent effective in preventing symptomatic infections in trials before variants emerged, was suspended in South Africa after a small study suggested it did not appear to protect against the variant there.

Dan Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center in Boston, whose lab helped design the vaccine, said protection against the variant was “quite good,” although he said that all vaccine developers are preparing for the possibility they will need to redesign vaccines for the variants.

There was also preliminary evidence that the vaccine may protect against asymptomatic infections, a key question about vaccines throughout the pandemic.

Blood tests from 2,650 study participants showed that two months after being vaccinated, 37 trial participants who received the placebo had evidence of asymptomatic infection. But only 10 of the participants who received the vaccine had similar markers in their blood. That suggested the vaccine reduced by 74 percent the threat of asymptomatic infection.