Saturday, April 17, 2021

FDA review confirms safety, efficacy of single-shot Johnson & Johnson coronavirus vaccine, especially against severe cases

Feb 25. 2021
Sean Kirk, executive vice president of manufacturing and technical operation, visits employees in a lab at Emergent Biosolutions, which is manufacturing vaccines for AstraZeneca and Johnson & Johnson, on Feb. 8, 2021 in Baltimore. MUST CREDIT: Washington Post photo by Michael Robinson Chavez
Sean Kirk, executive vice president of manufacturing and technical operation, visits employees in a lab at Emergent Biosolutions, which is manufacturing vaccines for AstraZeneca and Johnson & Johnson, on Feb. 8, 2021 in Baltimore. MUST CREDIT: Washington Post photo by Michael Robinson Chavez
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By The Washington Post · Carolyn Y. Johnson, Laurie McGinley

WASHINGTON - 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 manufacturing 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 one-shot 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% effective at preventing severe illness, including in areas of the world where concerning variants are circulating, but only 66% 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% - 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% 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% 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% effective in a British trial, but that protection fell to about 50% in South Africa. The vaccine developed by AstraZeneca and the University of Oxford, which was estimated to be 76% 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 laboratory 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.

Barouch's work in monkeys provides a clue as to why the vaccine's protection may have remained robust against the variant. Studies have shown that antibodies triggered by various vaccines are less effective against the variant first detected in South Africa, leading to fear that vaccines would no longer be protective. But those antibody tests don't capture the full immune response, and his work showed that the response from another prong of the immune system, T cells, is triggered strongly by the Johnson & Johnson vaccine in animals.

"The J & J vaccine, if it is approved by the FDA, is going to increase vaccine supply for the country and the world," Barouch said. "That's incredibly important, because we need to immunize our country and our world as quickly as possible to end this pandemic and to prevent the emergence of new variants in the future that might be even more concerning than the current ones."

The results suggest that the protection generated by the vaccine will prevent people from the worst outcomes, even if it allows some cases of coughs and fevers to slip by. The vaccine was more than 80% effective at preventing severe illness in South Africa.

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% the threat of asymptomatic infection.

The FDA, which on Monday issued new guidance to manufacturers on how to deal with variants, has emphasized being ready to possibly update vaccines. To streamline the process for getting clearance for modified vaccines, the FDA said, companies will be able to submit smaller studies testing immune responses in people's bodies rather than lengthy, large trials in which researchers give half the participants a placebo and wait to see if people get sick or not.

Several manufacturers, including Johnson & Johnson, are studying potential modifications to their vaccines to counter variants such as those first detected in the United Kingdom and South Africa.

The FDA described the vaccine as having a "favorable safety profile," with the most common side effects including pain at the injection site, headache and fatigue. It said one patient had a "serious event of a hypersensitivity reaction" - an allergic reaction that was not classified as anaphylaxis - two days following vaccination.

If an emergency use authorization is granted, about 2 million doses are expected to be shipped to states next week, while another 1 million to 2 million doses could be sent directly to pharmacies and other sites, federal officials said. That will make only a slight dent in the vaccine shortage affecting the nation. But supply will ramp up quickly in April.

In Europe, where the vaccine from AstraZeneca and the University of Oxford is available in addition to Pfizer-BioNTech and Moderna, societal debate has flared over whether people should be able to choose which vaccine they get.

"We have a really important job to do on how we message this," said E. John Wherry, an immunologist at the University of Pennsylvania. "The day that an individual has a choice on which vaccine to get - that's a great day, but probably won't be until summer." Until then, he said, people should take the vaccine they can get, because all are robustly effective.

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