FDA advisers unanimously recommend Johnson & Johnson’s Covid-19 vaccine

A panel of expert advisers to the Food and Drug Administration (FDA) voted unanimously on Friday afternoon to recommend the one-dose Covid-19 vaccine developed by Johnson & Johnson for an emergency use authorization. The next step is for the FDA to accept the recommendation, which could happen as soon as this weekend, clearing the way for distribution.

Earlier this week, the FDA posted a briefing going over the results of the phase 3 clinical trials of the Johnson & Johnson vaccine, which included 40,000 participants in several countries divided randomly into placebo and treatment groups.

The most important finding: The vaccine was 100 percent effective after 28 days at preventing deaths and hospitalizations from Covid-19 among the clinical trial participants who received the treatment. (Two vaccine recipients were hospitalized with Covid-19 two weeks after receiving the injection.)

The vaccine was also 66.1 percent effective at preventing symptomatic Covid-19 illness after four weeks, with consistent results across all age groups. When looking at blocking severe and critical cases of Covid-19, the Johnson & Johnson vaccine was 85.4 percent effective.

Mathai Mammen, global head of research and development for Janssen Pharmaceutical Companies, said during a press conference last month that the vaccine also had “plain vanilla safety results,” with the vast majority of recipients experiencing no problems. Most of the reported symptoms were mild, including fatigue, arm pain, and fever.

The efficacy levels against severe to critical Covid-19 changed depending on where the vaccine was tested. It was 85.9 percent in the United States after four weeks, while in South Africa, where a coronavirus variant with worrisome mutations that help it escape vaccines has been spreading widely, efficacy against severe disease was reduced to 81.7 percent.

Health officials say that while the Johnson & Johnson efficacy results are not as high as those from Moderna and Pfizer/BioNTech, the two vaccines that have already received emergency use authorizations from the FDA, the new vaccine’s performance is still superb.

“If this had occurred in the absence of a prior announcement and implementation of a 94, 95 percent efficacy [vaccine], one would have said this is an absolutely spectacular result,” said Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, during the press conference last month. The vaccine was developed by Janssen Pharmaceuticals, a division of Johnson & Johnson based in Belgium, together with Boston’s Beth Israel Deaconess Medical Center.

But unlike the vaccines from Moderna and Pfizer/BioNTech, Johnson & Johnson’s doesn’t require a booster shot, circumventing the two-dose problems posed by its competitors. There’s no need to track people down for their second dose, which means more people could be vaccinated faster. The shots also don’t require deep-cold storage, which means they’re less costly and somewhat easier to distribute.

“It’s a complete game changer,” said Georgetown University health law professor Lawrence Gostin. “It completely changes the equation.”

The Johnson & Johnson vaccine is also different in another way. It uses an adenovirus vector to deliver instructions for making the spike protein of the coronavirus, which is also less expensive to manufacture than the mRNA platform used for the other vaccines. (It’s estimated to cost around $10 per vaccine dose — roughly half the cost of the Pfizer/BioNTech vaccine.)

Johnson & Johnson has promised enough vaccines for 20 million Americans by the end of March and 100 million Americans by the end of June despite production challenges. It would be a huge boost to the 65 million Covid-19 vaccine doses that have been administered in the US so far.

So even with an overall efficacy level that’s lower than the two other vaccines on the US market, the Johnson & Johnson vaccine could become a major player. It’s the vaccine that “can increase equity,” said Saad Omer, the director of the Yale Institute for Global Health, particularly “if it’s deployed strategically in nations that are hard to reach and where that would be a particular challenge under a two-dose schedule.” Johnson & Johnson expects to distribute a billion doses of its vaccine worldwide this year.

But as amazing as it is to see several effective Covid-19 vaccines developed in record time, it’s now clear that the technology alone won’t save the day. An orchestra of supply chains, manufacturing, logistics, staff, and public trust needs to harmonize in order to actually get billions of shots into arms around the world and finally draw the pandemic to a close. And we also have other hurdles to overcome: controlling the spread of variants that seem to be threatening the effectiveness of all the vaccines we have.

What we learned about the safety and efficacy of the Johnson & Johnson Covid-19 vaccine

Johnson & Johnson launched separate clinical trials testing both a one-dose and a two-dose regimen to see how well these strategies provided long-term protection against Covid-19. The one-dose phase 3 trial arm yielded efficacy results first.

But hints that this vaccine could be safe and effective have been trickling out for months. The company published some of its early phase 1 and phase 2 trial data in a preprint paper in September, and the final version of the paper in January, in the New England Journal of Medicine. The papers showed the vaccine was well tolerated among the participants, and seemingly very effective: With one dose, after 29 days, the vaccine ensured that 90 percent of participants had enough antibodies required to neutralize the virus. After 57 days, that number reached 100 percent.

“When I looked at that, I thought, wow, this Johnson & Johnson product is very powerful after the first dose in terms of immunogenicity,” said Monica Gandhi, a professor of global medicine at the University of California San Francisco. “The Pfizer and Moderna vaccines needed two doses to get that level of [virus] neutralization.”

Like Pfizer/BioNTech, Johnson & Johnson “didn’t rush to phase 3 [trials],” said Hilda Bastian, a scientist who has been tracking the global vaccine race. Instead, it tested multiple vaccine doses and candidates at the outset to figure out which might perform the best in humans, and then proceeded through clinical trials.

The vaccine was also tested in nine countries — the largest single international phase 3 trial in the world, with more than 60,000 participants — meaning many ethnic groups were represented in the data, Bastian said. “As if all that’s not enough, it’s one of the ones that could be manufactured in South Africa and other places,” since Johnson & Johnson has manufacturing capacity around the world, even in countries hard-hit by the pandemic that have been waiting for vaccine supplies, she added.

The day this vaccine gets approval “is going to be a big day for the future of this pandemic [and] a ticket out of this disease for a larger part of the world,” said Nicholas Lusiani, a senior adviser at Oxfam America.

How adenovirus vector vaccines work

Part of the appeal of this vaccine lies in the technology behind it. Adenoviruses are a family of viruses that can cause a range of illnesses in humans, including the common cold. They’re very efficient at getting their DNA into a cell’s nucleus. Scientists reasoned that if they could snip out the right sections of an adenovirus’s genome and insert another piece of DNA code (in this case, for a fragment of the new coronavirus), they could have a powerful system to deliver instructions to cells.

For decades, scientists have experimented with adenovirus vectors as a platform for gene therapy and to treat certain cancers, using the virus to modify or replace genes in host cells. More recently, researchers have found success using adenoviruses as vaccines. Already, an adenovirus vector vaccine has been developed for the Ebola virus.

In addition to Johnson & Johnson and AstraZeneca/Oxford, CanSino Biologics of China is also developing an adenovirus vector Covid-19 vaccine; Russia’s Sputnik V Covid-19 vaccine uses this platform, too.

To make one of these vaccines, the adenovirus is modified so that it can’t reproduce but can carry the instructions for making a component of a virus. In the case of Covid-19, most adenovirus vector vaccines code for the spike protein of SARS-CoV-2, the part the virus uses to begin an infection.

Human cells then read those instructions delivered by the adenovirus and begin manufacturing the spike protein. The immune system recognizes the spike proteins as a threat and begins to build up its defenses.

Since adenoviruses exist naturally, they tend to be more temperature-stable than the synthetic lipid nanoparticles that are used to deliver the mRNA in the Moderna and Pfizer/BioNTech vaccines.

“The nice thing about the adenovirus vector vaccines is that they’re a little more tolerant to a longer shelf life, to the conditions of storage,” said Angela Rasmussen, a virologist at Georgetown University. Adenovirus vector vaccines can be stored at refrigerator temperatures, while mRNA vaccines need freezers, with Pfizer/BioNTech’s vaccine requiring temperatures of minus 80 degrees Celsius.

This helps lower the cost and complexity of manufacturing, distribution, and administration of adenovirus vector vaccines compared to other platforms. And simply having another vaccine on the market, made by a major pharmaceutical company with its own manufacturing infrastructure, is a big step forward. “The more vaccine doses we can have, the better,” Rasmussen said.

What comes next

The next challenge for Johnson & Johnson, after getting a green light from the FDA, is actually delivering doses to millions of arms.

But with three vaccines eventually on the market, should people hold out for any one vaccine in particular?

“Right now when people ask me, which, you know, which vaccine should I get? It’s pretty easy to answer that question because it’s whichever one you get offered,” said Paul Sax, a professor of medicine at Harvard Medical School. Vaccine supplies are limited, the transmission of the virus is high, and hospitals are close to capacity, so few people can be picky about what they get.

On the other hand, once vaccine supplies stabilize, having multiple vaccines with different characteristics could allow doctors and public health officials to optimize how the shots are distributed. “If the efficacy [of a given vaccine] is lower but still pretty good, there may be a scenario that one vaccine is recommended for low-risk populations and another one is for a high-risk population,” Omer said.

Though the Johnson & Johnson vaccine does have some key advantages over its competitors, it could face some of the same distribution snags that have hit other vaccines, like miscommunication between the government and hospitals, and production hurdles.

Researchers say that all the manufacturers also need to start working to get vaccines to the rest of the world. The new variants that have emerged in the UK, Brazil, and South Africa and have been detected in other parts of the world are reminders that the virus continues to evolve, and that a partially vaccinated population could exert more selection pressures that accelerate these mutations. So vaccination has to happen fast, and globally — and Johnson & Johnson’s vaccine may be a critical tool to do this.

“Long term, we need to be thinking about getting vaccines out equitably to the entire world, and having vaccines that are easier to distribute in terms of the cold chain requirements is going to be huge in that regard,” Rasmussen said.

But even as these vaccines roll out, there’s still more to learn: how long protection from vaccines last, whether there are any rare complications to consider, whether they prevent transmission as well as disease, and how well these vaccines work against the new variants. There are already some troubling signs of how these variants might eventually be able to evade vaccines. Continuing clinical trials will be critical, Sax said.

“You know, we’ve got millions of people who’ve received these vaccines already, which is exciting,” he added. “We’re on our way.”

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