An advisory panel on Friday recommended the Food and Drug Administration grant an emergency use authorization for Johnson & Johnson’s Covid-19 vaccine developed by Johnson & Johnson, which would become the third vaccine authorized in the United States and the first to require a single shot.

In a statement issued shortly after the vote, the FDA said it has told the company regulators “will rapidly work toward finalization and issuance of an emergency use authorization.” The agency also said it has notified federal partners involved in vaccine distribution “so they can execute their plans for timely vaccine distribution.”

Authorization of J&J’s vaccine could be a potential game changer, at least in some areas. Made by J&J’s vaccine division, Janssen Pharmaceuticals, the single-dose vaccine does not need to be frozen when it is shipped and distributed. The vaccine is what’s known as “fridge stable,” meaning it can be shipped and stored at the temperature of a regular refrigerator. Both those characteristics will make this vaccine much easier to deploy if the FDA authorizes its use. The two vaccines already in use in the United States, from Moderna and the Pfizer-BioNTech partnership, are both two-dose vaccines with onerous cold-chain requirements.

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Although the FDA does not have to follow the recommendation of the panel, known as the Vaccines and Related Biological Products Advisory Committee or VRBPAC, it is widely expected to do so.

The J&J vaccine hasn’t been tested yet in children and teens under the age of 18, so it will not be authorized for use in them.

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The J&J vaccine was found to reduce cases of moderate to severe Covid infection by 66.1%, starting 28 days after the single shot. (It takes a while for the protection of the vaccine to build up.) Results released in late January suggested the vaccine worked better in some areas than others; in the U.S., the vaccine was 72% protective.

An FDA analysis of the J&J data, released on Wednesday, suggested the vaccine was a little less effective against a virus variant first spotted in South Africa, known as B.1.351. But its protection did not appear to be eroded by a variant first spotted in Brazil, known as P.2.

The United States has purchased 100 million doses of the J&J vaccine, but supplies are expected to be scarce until at least April.

STAT’s coverage of the meeting is below, with updates and analysis posted in reverse chronological order.

What the vote means, according to the panelists

6:05 p.m.: The committee evaluating J&J’s vaccine voted 22-0 that its benefits outweigh its risks. That compares to a 17-4 vote for the first authorized Covid-19 vaccine, made by Pfizer and BioNTech, and a 21-0 vote, with one abstention, for Moderna’s vaccine.

That doesn’t mean, however, that this vaccine is the best one, according to public comments made by panelists themselves after they voted. Rather, several said the vote represents an increased confidence on their part in the FDA’s emergency use authorization process, and a feeling that the system is working thanks to the success of those earlier vaccines.

Patrick Moore of the University of Pittsburgh noted that when the Pfizer/BioNTech vaccine was the first to go through the EUA process, there were data from 45,000 volunteers, about the same amount now available for the J&J vaccine. But 55 million people have now received one of the two available vaccines, he said, and “things are looking good.” He added: “This process does seem to have worked despite my concerns about it six months ago.” 

Moore said he wanted the public to know that experts are thinking hard about these decisions during the health emergency. Arnold Monto, a University of Michigan professor and chair of the panel, agreed.

“The increased confidence in the process should be measured by the changing votes that we’ve had in subsequent reviews,” Monto said.  “We’re very comfortable with the procedure as well as the vaccines we are approving.”

— Matthew Herper

The vote
5:05 p.m.: The panel voted on only a single question: Based on the totality of scientific evidence available, do the benefits of the Janssen Covid-19 vaccine outweigh its risks for individuals 18 years of age and older?

The results were unanimous — all 22 panelists voted yes. Now, there will be a discussion on why the panelists voted the way they did, which could be as important as the vote in determining how the vaccine is authorized.

— Matthew Herper

The elephant in the room didn’t garner much discussion

4:50 p.m.: J&J’s data on the one-dose vaccine’s effectiveness in older adults aren’t spectacular; they really didn’t have that much, especially for adults 75 and older. It doesn’t mean the vaccine doesn’t work in older adults; it may. But the trial didn’t prove it. In the FDA’s analysis of the J&J data, posted online earlier this week, the agency said the data in people 75 and older had “limited interpretability” because of small numbers.

Their analysts didn’t even try to calculate a vaccine efficacy ratio for people in that age for the period of 28 days and later after vaccination. And some of J&J’s data raises questions about how well the vaccine works in adults 60 and older who have comorbidities, or underlying medical conditions. (Comorbidities are not rare in adults over the age of 60.) Looking at adults 60 and older with comorbidities from 28 days after vaccination, the vaccine efficacy estimate was 42%, but that lower figure could just due to chance given the smaller number of Covid cases in that group.

Yet there were surprisingly few questions about the lack of evidence for the vaccine’s efficacy in older adults. Even FDA’s Peter Marks, director of the Center for Biologics Evaluation and Review, seemed taken aback — he jumped into the discussion at a point to ask committee members to give FDA some indication of how comfortable they were about the evidence to support use of the vaccine in the older adults and the elderly.

“It would be good to hear some comments about that,” Marks noted.He didn’t get much in reply.

Panelist Mark Sawyer, a professor of pediatrics at the University of California San Diego, asked if J&J could peek at data being generated in its ongoing trial testing two doses. (Not currently, the company said. The trial is double blinded.) Panelist Melinda Wharton, director of CDC’s immunization services division, asked if there had been additional data generated by the one-dose study that could shed more light on the question. (Yes, said the company. But it is also still blinded.)

And that was that.

— Helen Branswell

One dose or two doses, Part 2

4:35 p.m.: To understand what’s coming next, you need to know that J&J has been conducting two clinical trials in the United States, a 44,000-person trial testing one dose, and a 30,000-person trial testing two doses. The amount of antigen used in the one-dose trial is higher than the amount used in the individual doses in the two-dose trial.

Ofer Levy, a Harvard University vaccinologist, asked Janssen’s Johan Van Hoof whether the company considered testing an intermediate dose, or testing whether an adjuvant — a compound that boosts the response to a vaccine — could improve the vaccine’s effectiveness.

Van Hoof said the company is actually studying whether giving “a very late boost” with “a small amount of antigen” to people who got the one-dose regimen would heighten the protection they get from the vaccine. He didn’t provide any details on how late late is, or how small small is. The work is ongoing, Van Hoof said.

— Helen Branswell

Is this really a one-dose vaccine? Or a two-dose vaccine?

4:10 p.m.: As Matt noted earlier, there are questions being raised about whether the J&J vaccine is a one-dose vaccine or whether a 30,000-person trial still under way is going to show the vaccine really should be given in two doses. That trial isn’t expected to report until some time in May.

Marion Gruber, FDA’s director of the Office of Vaccines Research and Review, jumped into the discussion a few minutes ago, possibly to avert problems later on in the voting.

Gruber noted that the application before the FDA at this point is for an emergency use authorization of a one-dose vaccine. If data that come in down the road suggest two doses of this vaccine are needed or at least better, that issue could be addressed when J&J applies for full licensure of the vaccine.

— Helen Branswell

Will being vaccinated make people less sick if they get Covid?

3:50 p.m.: James Hildreth, a panelist and the CEO of Meharry Medical College, asked if there was any evidence that people who develop Covid after receiving the vaccine experience milder illness than those who developed Covid in the placebo group.

Johan Van Hoof, from J&J, referred him to page 65 of the company’s briefing document. According to that document, the score on a questionnaire about symptoms was reduced 24% on day one for those who received vaccine compared to those in the placebo group on day one of the infection, and by 55% on day 14. Those who received the vaccine reported four to six symptoms, while those in the placebo group reported seven to nine symptoms. Those last two numbers are from a post-hoc, or after-the-fact, analysis, which makes them less reliable. Still, Hildreth said, this is an important thing to communicate to the public.

— Matthew Herper

Analysis of adverse events

3:30 p.m.: The FDA’s analysis of side effects from vaccination focused on clotting disorders, tinnitus (buzzing or ringing in the ears), and urticaria, better known as hives.

For all three conditions, the agency’s scientists concluded there might be a link between receipt of the vaccine and the side effects, though the numbers were very small. For two — the clotting conditions and tinnitus — they said vaccine could not be ruled out as a possible contributing cause; for urticaria, they said there was a plausible relationship to vaccination.

When you read these numbers, keep in mind that this was a study involving 44,000 people.

There were six cases of tinnitus among people who got vaccine versus none in the placebo arm of the trial. Half of the tinnitus cases occurred within two days of vaccination, the other three began within 12 to 22 days of vaccination.

Among the clotting events, there were six cases of deep vein thrombosis in the vaccine arm, compared to two in the placebo arm. There were four pulmonary embolisms — clots in the lungs — in vaccine recipients, compared to one in a person in the placebo arm. And there was one case of sinus venous thrombosis, a blood clot in the brain’s venous sinuses, in a vaccine recipient.

With both the clotting events and the tinnitus, the FDA said the people involved had other health problems that made it difficult to determine whether receipt of the vaccine might have played a role.

There were eight cases of hives among vaccine recipients, compared to three among placebo recipients.

The FDA also concluded three serious adverse events were likely linked to receipt of the vaccine. A 42-year-old man had a hypersensitivity event — he developed a widespread rash and his lips swelled within a few days of vaccination, and a 30-year-old man had injection site pain that spread to include more of his arm. Finally, a 35-year-old man developed extreme generalized weakness, fever, and a headache on day 2 post injection and was hospitalized but recovered.

— Helen Branswell

Communicating with the public about vaccines is about get more difficult

2:55 p.m.: One thing that’s been clear from the panel discussion about J&J’s vaccine: The job of communicating with the public about Covid-19 vaccines, already a minefield, is about to get more treacherous.

During late morning discussion, Paul Offit, a panelist and a well-known vaccine researcher at Children’s Hospital of Philadelphia, asked how J&J plans to shift its communication if, in the end, this ends up being a two-dose vaccine. In its first trial, the company tested a single dose. But a second, 30,000-patient trial aims to test a two-dose regimen.

Offit’s question: What if the two-dose regimen works better? How do we explain that to the public?

Questions like that are going to be more fraught, and Offit, who has written at length about the way discussion about the vaccine preservative thimerasol backfired and led to unwarranted vaccine skepticism, is well aware of it.

In the open public hearing, Diana Zuckerman of the National Center for Health Policy Research made a different point. Many public health experts are emphasizing that the vaccines prevent severe Covid or death. But the number of severe cases is small, and the number of deaths is even smaller. It’s misleading, she said,  to tell the public that nobody who got the vaccine was hospitalized unless you also tell them that only five people were hospitalized.

Nabarun Dasgupta, a senior scientist at the University of North Carolina, made a plea for apps being used to track side effects to offer more to users, lest those people don’t participate in research. But he made another complicated point. Right now, people don’t get a choice of which vaccine they are going to receive. But for groups that are vaccine hesitant, he argued, the ability to choose which vaccine they receive could make them more willing to get vaccinated, because it will give them a sense of agency.

Nobody said it would be easy.

—Matthew Herper

Anaphylaxis again rears its head

12:35 p.m.: Cases of anaphylaxis have been reported after receipt of both the Pfizer and the Moderna vaccines. There had been no reports of this severe, life-threatening allergic reaction in people who have received the J&J vaccine. Up until now.

Macaya Douoguih, head of clinical development and medical affairs for Janssen, J&J’s vaccines division, told the panel that on Wednesday, the company was informed that someone who was taking part in an open-label study in South Africa developed anaphylaxis after receiving the vaccine. (In an open-label study, both participants and researchers know whether a participant is getting vaccine or a placebo.)

Anaphylaxis requires rapid administration of epinephrine to combat the closure of airways that the reaction triggers. The CDC requires people administering Covid vaccines to monitor people for 15 minutes after vaccination, and 30 minutes for people in whom the risk of anaphylaxis after vaccination is high.

The CDC has been monitoring anaphylaxis events in the vaccine rollout. In a presentation earlier today CDC’s Tom Shimabukuro reported that to date it is seen at a rate of about 4.7 cases per one million doses of the Pfizer vaccine and 2.5 cases per one million doses of the Moderna vaccine.

— Helen Branswell

How J&J’s vaccine works

12:20 p.m.: Hanneke Schuitemaker, J&J’s global head of viral vaccine discovery, presented a discussion of how the J&J vaccine works and how it was developed.

The vaccine is a modified cold virus, known as an adenovirus. The modified virus, known as a vector, is called Ad.26. One gene was deleted to make Ad.26 unable to replicate in humans. A second gene was deleted to make room for a synthetic gene, called a transgene, that is added to the virus. The FDA classifies the vector as non-replicating, meaning that this won’t change the DNA of the volunteer’s cells.

Instead, the virus infects cells in the vaccine recipient and makes lots of copies of a protein coded by this transgene, which the immune system then learns to recognize and attack. In this case, as with other Covid-19 vaccines, this is a copy of the spike protein, which SARS-CoV-2 uses to enter human cells. J&J tried multiple versions of this spike protein to create a vaccine with what Schuitemaker called “optimal stabilization, expression, immunogenicity, efficacy.”

The vaccine prevented non-human primates from being infected through their lungs, and almost eliminated SARS-CoV-2 virus in their noses.

A single dose of the vaccine also clearly reduces cases in humans. Macaya Douoguih, another J&J scientist, presented data from J&J’s clinical trials which showed the vaccine reduced the risk of severe disease. Still, the numbers are small. There appear to have been 6 deaths from Covid-19 observed in the study, none of them in patients who received the vaccine. All of them were in South Africa, where the B.1.351 strain has become prevalent.

—Matthew Herper

J&J plans for studying its vaccine in special populations

11:40 a.m.: Johan Van Hoof, managing director of Janssen Vaccines, J&J’s vaccine division, told the panel that a trial to study the safety and efficacy of the company’s vaccine will begin in late March or early April. It plans to study the vaccine in children under the age of 17, with a trial in adolescents to start soon.

The company also plans to study the safety and efficacy of the vaccine in people who are immunocompromised in the third quarter of this year.

— Helen Branswell

So far so good on data during pregnancy

11:15 a.m.: There was good news for pregnant people reported in a presentation on the safety data that are emerging from use of Covid vaccines.

Tom Shimabukuro from the Centers for Disease Control and Prevention reported on the monitoring of people who received a Covid vaccine while pregnant. The safety of the vaccines hasn’t yet been proven in this population because pregnant people were excluded from the clinical trials. Pfizer announced earlier this month it had started a Phase 2/3 trial to determine whether its vaccine is safe and effective in this important population group.

Shimabukuro said to date there have been 154 adverse events reported by pregnant people in the Vaccine Adverse Event Reporting System, which is operated by the CDC and the FDA. About half of those people report having been vaccinated in the first 13 weeks of their pregnancies.

Most of the adverse events reported were not related to pregnancy — things like headache, fatigue, chills, and reactions at the injection site, Shimabukuro said. There were 29 spontaneous abortions or miscarriages reported, but about 10% to 20% of all pregnancies end through spontaneous abortions or miscarriages, he noted.

“The number was not concerning considering the expected background rate,” Shimabukuro said.

The CDC, through its V-safe vaccine safety surveillance system, is maintaining a registry of people who report they were pregnant following vaccination. They are being followed, with check-ins every three months and another three months after the birth of the baby. There are 1,815 people in the pregnancy registry so far.

Overall, Shimabukuro’s update suggested no concerning safety signals have emerged so far related to the Covid vaccines currently in use in the United States. “Anaphylaxis does occur, though rarely, and there are no safety signals for any serious adverse events,” he told the panel.

— Helen Branswell

New data drive home the threat from coronavirus variants

10:30 a.m.: Adam MacNeil, an epidemiologist at the Centers for Disease Control and Prevention, showed the panel new data on the three SARS-CoV-2 variants researchers have been most worried about: B.1.1,7, B.135.1, and P.1. The grim message: Variant strains of the virus are dangerous and widespread.

All three of those variants have been detected in the U.S.  “We have to assume in the absence of other information that these variants probably could exist throughout the entire U.S.,” he said.

The B.1.1.7 variant has become the predominant strain in the U.K. and in much of Europe. MacNeil presented conclusions from unpublished data reviewed by the New and Emerging Viruses Threats Advisory Group that deaths and hospitalizations were 1.7 times higher with the new variant, which are thought to have arrived in the U.S. in November. In models, a scaling up of vaccination could blunt the increase in cases from the variant.

B.135.1 is worrisome because it has shown the potential to reinfect previously infected or vaccinated people in some cases. (This means that the vaccines would become less effective, but would still protect against Covid-19.) MacNeil showed data from Zambia in which the B.135.1 variant, previously undetected, drove a 16-fold increase in cases in one month.

P.1. also seems to be able to overcome immunity. He described the experience in Manaus, Brazil, where an epidemic resulted in 76% of people having been infected. The emergence of P.1 resulted in a new spike in hospitalizations there, despite this apparent herd immunity.

MacNeil also said that right now, the U.S. is “nowhere close” to having herd immunity. The U.S. surveillance effort is scaling up, but it is still not at the scale needed to quickly identify new variants. He also emphasized that current strategies, like masking and social distancing, work and that vaccines, even with decreased effectiveness, vaccinations could still provide partial protection.

—Matthew Herper

Ho-hum?

9:35 a.m.: Has the excitement gone out of the prospects of emergency use authorizations for new Covid-19 vaccines? I ask because there are about 1,900 people watching the J&J hearing right now.

During the first VRBPAC hearing for a Covid vaccine, the Dec. 10 meeting on Pfizer and BioNTech’s vaccine, there were more than 15,000 people watching at points in the day.

— Helen Branswell

The path forward

8:10 a.m.: It seems a sure bet the VRBPAC will recommend that the FDA authorizes the J&J vaccine, and that FDA will do it quickly — as early as Saturday, perhaps.

Why do we think so? For one thing, the agency moved rapidly to issue EUAs for the Pfizer and Moderna vaccines. For another, the expert panel that issues recommendations to the Centers for Disease Control and Prevention on how vaccines should be used is meeting in an emergency session on Sunday to discuss the J&J vaccine. That group, the Advisory Committee on Immunization Practices, or ACIP, makes recommendations only after the FDA authorizes use of a vaccine. So, its Sunday meeting is a pretty solid clue.

If the FDA authorizes the J&J vaccine on Saturday and ACIP issues recommendations on Sunday, supplies of the vaccine could start to ship almost immediately. But as we said earlier, J&J doesn’t have a ton of vaccine to plug into the pipeline at this point. We’re hearing amounts in the very low millions of doses until April.

The vaccine will be entering the distribution program at a time when 46 million Americans have had a least one dose of vaccine and 21.5 million have received two doses — 8.4% of the population over 18 years of age.

It also comes at a time when new cases are declining and shortly after the country hit an ignominious mark — the U.S. death toll from Covid topped 500,000 people.

— Helen Branswell

VRBPAC’s agenda

7 a.m.: Good morning, STAT readers.

Your VRBPAC live-bloggers today are Matthew Herper and me, Helen Branswell.

For starters, let’s introduce you to the committee members. The FDA has a very strict conflict of interest policy for VRBPAC members. Anyone involved in any of the Covid-19 clinical trials — even a member who works at a university that is a trial site is “conflicted out,” which means that temporary replacements who are equally stringently vetted are named to sit in their place. Most of the members of today’s panel sat when VRBPAC evaluated the earlier two Covid vaccines.

The early part of the meeting, which begins at 9 a.m. EST, is mostly housekeeping. There’s a presentation on what emergency use authorizations are, and one on what surveillance data are indicating about the safety of the two Covid vaccines currently in use. There is also a session on the various virus variants — say that three times fast! — that are circulating and raising concerns about vaccine efficacy.

At 11:10 a.m. EST, a team from J&J will present their take on the data on their vaccine and will be questioned on it by committee members. After lunch — if there is a lunch break, VRBPAC meeting sessions often run long — FDA scientists will present their review of the data. And then VRBPAC members will be asked one or several questions by the FDA and will take one or several votes.

The meeting is meant to conclude at 5:30 pm. EST. We’ll see.

— Helen Branswell

Correction: An earlier version of this story misstated the number of Americans who have received at least one dose of Covid vaccine.

Source: STATNEWS.COM

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