J&J adcomm live blog: Committee votes 22-0 to recommend an FDA OK for the J&J vaccine, setting up 3rd US Covid-19 jab
The US could have a third authorized Covid-19 vaccine within hours.
The FDA’s advisory committee voted unanimously — 22-0 — to recommend the agency issue an emergency use authorization for J&J’s vaccine. If they follow the precedent of the Pfizer and Moderna vaccine, the FDA will likely authorize the vaccine by Saturday, immediately adding a few million doses to the US supply and adding a 100 million by June. An authorization would give the world its first single-dose vaccine, a major weapon in the effort to vaccinate the world and bring the virus to heel, particularly in rural and developing areas.
“I think it was a relatively easy call,” observed Eric Rubin, New England Journal of Medicine editor-in-chief and committee member.
One key concern throughout the day’s discussions centered around one subgroup in J&J’s trial: The shot appeared only 42% effective in adults over the age of 60 with comorbidities 28 days after vaccination. But committee members agreed that it was too small a population to draw sweeping conclusions from. Other evidence pointed to higher efficacy and the public health concern was too great.
“Despite the concerns that were raised in the discussion, we are still in the midst of this deadly pandemic,” Archana Chatterjee, dean of Chicago Medical School and a committee member said. “There is a shortage of vaccines that were authorized and I think this vaccine will help meet the need at the moment.”
FDA VRBPAC just finished reviewing Janssen Biotech (J&) COVID-19 vaccine and voted unanimously to approve issuing EUA. Definition of case severity was an issue but data clearly showed benefits outweighed risks as required for EUA.
— James E.K. Hildreth (@JamesEKHildreth) February 26, 2021
Multiple advisors emphasized that people should get whatever vaccine becomes available to them when it becomes available to them.
“In this environment, whatever you can get, get,” Committee chair Arnold Monto said.
J&J working on vaccine for variants, trial scheduled for summer
This week, Moderna announced it would begin testing a modified version of their mRNA vaccine to tackle the vaccine-resistant B1.351 variant that popped up in South Africa. Pfizer said it would test giving people an extra boost of its original vaccine to accomplish the same.
J&J revealed at the adcomm that they, too, have been working on a modified vaccine to tackle emerging variants.
The company didn’t reveal much detail, including how they modified the vaccine or if they were targeting the same B1.351 variant, but Johan van Hoof said they would begin testing a new construct in the summer. The FDA has said they would allow modified vaccines for variants to be authorized after quick immunological studies that track whether the vaccine elicits antibodies against the new variant.
4:15 J&J faces questions on older adults, asymptomatic infection, long-term immunity
The FDA adcomm has advanced to the free-for-all question stage of the hearing and, as they did for Moderna and Pfizer, committee members are raising questions about the lingering issues surrounding the vaccine.
In J&J’s case, one of those unknowns is a group of participants who appeared to respond worse to the vaccine: those over 60 with comorbidities. In that group, the vaccine was only 42% effective at stopping disease starting 28 days after vaccination.
Both J&J and the FDA avoided making any conclusions about the number, cautioning that there weren’t many people in that subgroup and it could just be a result of a too-small sample size. Still, Stanley Perlman, a coronavirus expert at the University of Iowa, questioned whether people in that group who receive the shot will feel like they’re receiving a second-class vaccine. (Moderna and Pfizer both saw around 90% in older adults.)
“People who receive this will feel like they’re getting a vaccine that doesn’t work as well,” Perlman said. “We don’t want to have two classes of participants and feel like we’re increasing health inequities.”
J&J’s Johan van Hoof noted in response that the vaccine was more than 60% effective in that group between day 14 and 28 and that the vaccine still appeared able to protect against severe disease, including death. The difference could just be a result of the placebo group.
“There’s no evidence of statistical significance,” he said.
Members also asked about how long protection lasts and how effective it is against asymptomatic infection. These questions also loomed over the Pfizer or Moderna for vaccine, although they differ for the J&J vaccine in a couple ways.
For one, J&J — unlike Pfizer and Moderna — has already collected data on asymptomatic infection from about 1,500 participants in both the placebo and treatment arms, offering preliminary data that the vaccine can reduce asymptomatic infection by around 70%. An actual answer, though, may lag significantly: J&J won’t make the final calculation until they have 6 months followup on 15,000 participants.
The technology behind J&J’s vaccine also changes the calculus for the long-term response. J&J uses a harmless adenovirus to deliver a gene for the coronavirus spike protein. But each time a person is exposed to that adenovirus, they develop antibodies against it — antibodies that might prevent booster shots from restoring immunity if it wanes in subsequent years.
Van Hoof, however, said they expect protection to last at least one to two years. And in trials for Ebola and HIV vaccines that use the same platform, they had little trouble upping antibody levels with shots in subsequent years.
“It seems to have no problem at all to get that booster response,” he said.
J&J is also testing a two-dose vaccine. What happens if it’s more effective?
J&J has spent the day touting the data behind their Covid-19 vaccine, but one advisor pointed that, in a few months, another batch of data could force them into a curious dilemma.
J&J was the only major vaccine developer to attempt to produce a single-dose vaccine, a huge asset when trying to rapidly inoculate the world against an ongoing public health threat, but they hedged their bets. Alongside their main Phase III trial, they also launched another that would test two doses, each spaced two months apart.
Results from the first trial are in: The vaccine is 66% effective at preventing mild illness and 85% effective against severe disease. As both the FDA and J&J have argued, that’s enough to provide a major weapon in the fight to bring Covid-19 under control.
The second trial hasn’t read out yet, though. What happens if it turns out that two doses are more effective than one?
“If we move forward with this vaccine and find that with two doses we have a better clinical response, does this then become a two dose vaccine?” Paul Offit, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia, asked. If positive data eventually come in, should people who get the vaccine in the coming weeks “come back for a second dose?”
J&J vaccine executive Johan van Hoof didn’t directly answer the question but he touted repeatedly the potential public health benefits of a single-dose shot.
“In the situation of an outbreak, in a raging epidemic, the big challenge is to get the epidemic under control,” Hoof said. “And that is where a single-dose vaccine with rapid onset of protection is highly preferred.”
Offit agreed, but he said J&J may face a messaging problem if people hear that a second dose will be more effective.
1:26 New case report means anaphylaxis concerns aren’t going away
When the UK and the US authorized the Pfizer and Moderna vaccines and a tiny handful of recipients developed anaphylactic reactions, researchers theorized that the culprit may have been the lipid nanoparticle — the tiny bubble of fat used to encase and deliver mRNA into cells.
At the FDA hearing, though, J&J’s head of medical affairs Macaya Douoguih revealed that on Wednesday, the company was informed that one of the participants in a new open-label study in South Africa went into anaphylactic shock after receiving a dose of their vaccine, which uses a different technology that doesn’t involve lipid nanoparticles.
While serious, anaphylactic reactions are both exceptionally rare (about 2.5 per million for Moderna and 11.1 per million for Pfizer, according to a recent JAMA study) and easy to handle: Recipients are monitored for 15 minutes after injection and, in the unlikely event there’s a reaction, given epinephrin.
Still, the new report means the issue is one doctors and officials will have to consider for perhaps all vaccines and for the lengthy remainder of the global vaccination effort.
11:10 Will variants impede a long-sought goal for Covid-19 research?
The Covid-19 vaccine trials have been an all-but unmitigated success, laying the basis for vaccines that have since brought the virus to heel in locations where they’ve been rolled out. But they are also long and laborious and will be increasingly difficult to run as more people become eligible for an authorized vaccine and unwilling to risk getting a placebo.
That’s why vaccinologists have been working all year to establish an immune correlate of protection — a precise mix of antibodies that, with a simple blood test, can determine whether someone will be protected. It’s how new flu vaccines are approved and it could allow new Covid-19 vaccines to reach market at a far brisker pace.
As CDC epidemiologist Adam MacNeil presented on new variants, though, FDA committee members questioned whether mutated versions of the virus could jeopardize that goal. If new variants, such as the B1.351 one that emerged in South Africa, escape the mix of antibodies induced by current vaccines, wouldn’t that make it difficult to find a single standard for how many and what kind of antibodies offers protection?
“It may be a moving target,” MacNeil said.
It’s a question, MacNeil said, that will loom over the coming years as researchers monitor a virus that is not going to vanish and try to determine whether and how to update vaccines.
“Will we need annual updates like influenza?” he said. “Will we need annual updates every five years? Or will we have broad enough protection to in essence use a steady-state vaccine?”
10:21 Panelists question EUA endpoints as new variants emerge
Greetings from the first technical difficulties of the FDA advisory committee for J&J’s Covid-19 shot.
The audio went out on the live stream at about 9:30am and after about 5 minutes of unhalted discussion, they sent viewers to a “time for a break” page. While they sort that out — occasionally acting chair Arnold Monto’s voice breaks through the indie hold music, so could be soon — we’ll fill you in on the hearing so far.
The first hour or so of an adcomm is largely logistics, including introducing the committee and outlining the legal basis for emergency use authorization members. Before the audio dropped, though, a few committee members were able to ask questions and they centered in part over what the right endpoints should be for an EUA.
Over the summer and fall, the FDA issued guidelines that any vaccine developer would have to prove their vaccine was at least 50% effective at stopping disease and follow trial participants for at least two months for safety. With two mRNA vaccines already authorized and hugely effective, Monto asked, have those standards changed at all?
Cody Meissner, head of pediatric infectious disease at Tufts Medical Center, put the question differently: J&J’s vaccine proved less effective — 66% compared to 95% — at preventing mild disease than the mRNA vaccines, but they conducted the trial at a time when new variants of the virus had arisen, including a variant in South Africa that has proven vaccine-resistant. At the same time, the J&J vaccine still proved highly effective at preventing hospitalization and death.
“Because the strains of SARS-CoV-2 that are circulating now may be somewhat different than the ones that were circulating during the trials for the messenger RNA, and so the efficacy at preventing relatively mild or even moderate disease might be different,” Meissner said. “But all the vaccine seem to be equally effective same for severe disease and death. Has the FDA considered that perhaps different endpoints should be considered in terms of granting an EUA in the future, as new vaccines apply for EUA?”
For now, the answer is no. Maria Allende, an FDA medical officer, said the FDA would keep the current endpoints until they can find immune correlate of protection — a blood test to see if participants have the right mixture of antibodies to protect against disease — and they would use surveillance and real-world monitoring mechanisms to track how well the vaccines work against new variants.
The standards for full approval have not changed either, she said in response to another question. The FDA would like 6 months of followup on trial participants to fully approve a vaccine, a benchmark that would put Moderna and Pfizer on the path to an approval application in the next couple of months.