A group of advisers to the Food and Drug Administration met on Friday to discuss whether the agency should clear Johnson & Johnson's coronavirus vaccine for emergency use.
Results from a large international study of roughly 40,000 volunteers found the shot was 66% effective in preventing moderate or severe COVID-19, although protection appeared weaker against a virus variant first detected in South Africa. FDA scientists reviewing the vaccine affirmed J&J's findings in documents published Wednesday.
The committee found J&J's and FDA's presentations convincing, voting 21-0 in support of the vaccine's benefit-risk profile.
While the positive review was expected, the gathered vaccine and infectious disease experts still had much to debate. BioPharma Dive tracked the day-long meeting and reported on the discussion here. The most recent entries are listed first.
Updated Monday, March 1, 1:30 pm
On Monday, the FDA confirmed to BioPharma Dive a corrected vote tally of 21-0 in support of J&J's vaccine, rather than the 22-0 reported at meeting.
"One individual accidentally selected the voting pod, but that vote was not read aloud for the record," an agency spokeperson said in an emailed statement.
The committee's 22-0 vote was non-controversial, with members expressing a growing comfort with the accelerated process of authorizing a vaccine for emergency use.
By contrast, the vote in December on Pfizer and BioNTech's vaccine was disrupted at the last minute over whether to support use for 16- to 18-year-olds. The Moderna vote also saw one member abstain based on the language of the FDA's voting question.
"It's a relatively easy call," said committee member Eric Rubin, editor-in-chief of the New England Journal of Medicine, of the decision on J&J. "It is a bit challenging how to use it clinically right now, but the demand is so large that it clearly has its place."
If the FDA's follows its past practices, an authorization decision will be issued late Saturday, with J&J ready to ship 3 to 4 million doses immediately and 20 million by the end of March. The Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices has scheduled an emergency meeting Sunday to review the vaccine.
Cody Meissner, a pediatric infectious diseases physician at Tufts Medical Center, left FDA reviewers with one final caution: "I think it's important that people don't believe one vaccine is better than the other," he said. "Hopefully, [CDC] will emphasize there is no preference for one vaccine over another." — Jonathan Gardner
J&J's vaccine is likely to be cleared by regulators imminently.
Asked whether the benefits of J&J's vaccine outweigh the risks in adults 18 and older, the committee voted 22-0 in unanimous support of the shot.
The vote should pave the way for an FDA authorization that could come as soon as Saturday. Both Pfizer's and Moderna's vaccines were cleared one day after positive recommendations from their FDA advisory panels. Both of those meetings took place on a Thursday, however, allowing a next-day decision to still be made during the work week. — Ben Fidler
Questioned by panelist Steven Pergam of the Seattle Cancer Care Alliance on its plans to address emerging variants, J&J appeared to take a similar stance as Moderna and Pfizer. It's confident in its shot, but preparing a backup plan.
Van Hoof pointed to the vaccine's apparent ability to prevent severe disease in people infected with the B.1.351 variant, and data suggesting the vaccine's protection might strengthen with time.
"The jury is still out" on whether J&J needs a modified vaccine, van Hoof said.
Nonetheless, J&J does have a variant-specific shot in the works that should be ready for Phase 1 testing "by the summer," he said. — Ben Fidler
Multiple panelists echoed Offit's concerns earlier in the day: What should be done if two shots of J&J's vaccine prove to be better than one in an ongoing trial?
Eric Rubin, an adjunct professor of infectious disease and immunology at Harvard, noted that this could occur after a "large number of people" have gotten a single dose, including clinical trial participants. "We want to have a way of capturing them," Rubin said. But it "seems like a big logistical problem."
After a few others chimed in, Marion Gruber, the director of the FDA's vaccine review division, described the issue more about logistics than anything else. The FDA has the ability to amend its emergency use authorization to allow for two doses, Gruber said.
"I understand there are logistical and operational issues that need to be sorted out," she said. "But from a regulatory perspective, we have the means to address this." — Ben Fidler
One concern about viral vector vaccines like J&J's has been whether people who receive one develop immunity against the vector, which could render the subsequent doses ineffective. (This point is also relevant to debate over redosing with gene therapies that use adeno-associated virus vectors.)
This appeared to occur in an early study of a vaccine developed by China's CanSino Biologics, which uses a different viral vector than J&J.
Under questioning from committee members, J&J's van Hoof cited examples from other vaccines based on its adenovirus platform, including a four-shot HIV vaccine regimen in which "you see a continuous rise in antibody levels," as well as a prototype HIV vaccine that was boosted several years later. "It seems that there's no problem at all to get a booster response," said van Hoof.
While he acknowledged that viral vector vaccine boosters could be undermined by immune response, "overall, the viral load that you give with the vaccine is sufficient to overcome this defense." — Jonathan Gardner
One unique aspect of J&J's trial was how the drugmaker counted cases of COVID-19. When measuring efficacy, J&J evaluated whether its shot prevented moderate or severe COVID-19, whereas Pfizer and Moderna sought to count all symptomatic cases in their respective studies.
The definitions are more similar than they are different, however. In each case, drugmakers were looking for at least one or two mild symptoms, like fever, or more serious ones, such as shortness of breath, alongside a positive coronavirus test result.
In the end, only four COVID-19 cases fell outside of the moderate or severe categories in J&J's trial, committee chair Arnold Monto noted.
"So can we conclude that really the moderate and severe case definition is just about equivalent to all symptomatic cases?" he asked FDA scientists.
FDA vaccine reviewer Rachel Zhang agreed, noting that the descriptions were "basically the same."
The agency's presentation, meanwhile, didn't contain any surprises that weren't addressed in briefing documents earlier this week. Zhang did note, though, that it was difficult to interpret the apparently weaker protection in certain groups, such as those 60 and older, because of small sample sizes. — Ben Fidler
The afternoon began with an open hearing, a forum for doctors, advocates, researchers and the general public to comment on J&J's vaccine and the FDA's review.
Most supported an emergency authorization, citing limited vaccine supplies and the ongoing pandemic threat. But there were a range of concerns voiced, including vaccine safety in pregnant women, unequal distribution of doses and continued follow-up for shots that receive emergency clearance.
One important voice of support came from Public Citizen's Sidney Wolfe, who frequently attends advisory committee meetings and can be critical of the FDA.
Several weren't happy with how the FDA has handled advisory committee meetings for coronavirus vaccines, however. As with Pfizer's and Moderna's shots, the perception is that J&J's vaccine is likely to be authorized regardless of the day's discussion.
Meetings for those vaccines featured some pushback from the committee on how the FDA asked for their recommendations, and the day-long meetings limit open debate among members to a roughly two-hour period in the afternoon. — Ned Pagliarulo
The vaccines authorized so far are for use in adults and adolescents over 16 only, at least until more data are available. J&J, however, was eager to point out that its technology — which uses an adenovirus vector to stimulate an immune response — has been used in children as young as 4 months old in clinical trials, giving some support for starting a pediatric trial of the coronavirus vaccine.
A trial in adolescents is due to begin next week, and will enroll younger age groups over the next few months, Johan van Hoof, head of vaccines R&D at J&J, told the advisory committee members.
He said J&J's experience with vaccines in children was a stronger immune response that led to more frequent side effects like fever, but characterized them as "manageable."
"We feel that the platform experience encourages us to start fast with our pediatric program," he said. — Jonathan Gardner
The chief advantage of J&J's vaccine, compared to others already authorized, is its one-dose regimen. A vaccine that can protect against COVID-19 after only one shot eases many of the distribution challenges countries now face, and helps stretch supply further.
But J&J is also running a large study testing two doses of its vaccine, with results expected later this year. What if a second shot provides even better protection?
Paul Offit, a vaccine expert from the Children's Hospital of Philadelphia, pressed J&J on this point, asking what would then happen to individuals who had received a single dose.
Johan van Hoof, who leads J&J's vaccine R&D, didn't have a straight answer, acknowledging the study could show higher efficacy. But he emphasized the protection offered by a single shot.
"It's clear in the situation of an outbreak, a raging epidemic, the big challenge is to get the epidemic under control," van Hoof said. "That's where a single dose vaccine with rapid onset of protection is preferred."
Offit pushed J&J to think through how it might communicate the results from the two-dose study, when they're available. "It's a messaging challenge," he said. — Ned Pagliarulo
During its presentation, J&J methodically broke down how its vaccine performed across a wide range of participant groups. For most groups, the vaccine was similarly effective against COVID-19.
Among adults 60 years and older who had one or more underlying risk factors, however, efficacy was noticeably lower, at 42% a month after vaccination. That figure is based on 41 cases of COVID-19, a relatively small number.
In its briefing documents, FDA scientists noted this apparently weaker protection, but said the estimate may be imprecise due to the sample size and could change if more cases are included.
"Our assessment is aligned with that of the FDA, that there's an observed trend of increasing efficacy with narrower confidence intervals, as numbers of cases in the analysis increase," said Macaya Douoguih, the head of one of J&J's vaccine divisions.
The company believes individuals 60 years and older with comorbidities are, in fact, similar to other groups and would likewise benefit from vaccination, Douoguih said. — Ned Pagliarulo
For more vaccines to quickly get to market — or for the existing ones to become available to children and, eventually, infants — determining how much of an immune response is needed to confer protection is a critical step. Identifying these so-called correlates of protection would help developers predict whether their shots are effective and avoid lengthier trials.
Variants, however, appear to have made that objective more difficult, because each might require different levels of neutralization, Meissner said. "The threshold of immunity will probably vary depending on the vaccine, and depending on the variants that circulate," he said.
MacNeil, the CDC official, agreed. A correlate of protection is now "a moving target," he acknowledged.
"The fundamental question as the outbreak progresses is, how is this virus going to behave?" he asked. "Are we going to need annual updates, like influenza … or will we have broad enough protection to use, what's in essence, a steady-state vaccine?"
For their part, Moderna and Pfizer have already begun preparing for a worst-case scenario by readying boosters or modified shots. J&J hasn't yet disclosed its plans. — Ben Fidler
Adam MacNeil, a deputy director within the CDC's immunization safety office, outlined what the agency refers to as "variants of concern." They are evolved versions of the coronavirus that have shown evidence of an impact on drugs or diagnostics; increased transmissibility or disease severity; and the potential to evade an immune response triggered by previous infection or vaccination.
The three variants of concern so far are well-known: B.1.1.7, first detected in the U.K.; B.1.351, which originated in South Africa; and P.1, which was first found in Brazil. B.1.1.7 is more transmissible than the original virus, while B.1.351 has a mutation to the coronavirus's spike protein that appears to reduce vaccine potency. P.1 has the same alteration, but hasn't been proven yet to affect vaccines.
MacNeil said the CDC is conducting surveillance and investigation of variants in the U.S., looking in particular for vaccine "breakthroughs," when infections occur despite immunization. The agency has seen roughly 1,600 cases caused by B.1.1.7; 22 cases of B.1.351; and 5 of P.1.
B.1.1.7 is expected to become the "dominant" strain in mid- to late-March, MacNeil said. But because it doesn't appear to affect vaccine potency, its impact could be substantially blunted by an aggressive uptick in vaccinations. — Ben Fidler
Since the advisory committee last met to vote on Moderna's vaccine, concerns over coronavirus variants have become much more acute. In particular, the B.1.351 variant, first identified in South Africa, has been shown to limit the potency of several vaccines, weakening the immune response to Moderna's and resulting in lower efficacy in Johnson & Johnson's trial sites in South Africa.
Committee member Cody Meissner, a pediatric infectious diseases physician at Tufts Medical Center, asked if the FDA had considered changing trial endpoints to account for the new variants.
Maria Allende, chief of the FDA unit in charge of J&J's application, said the current endpoint, which compares COVID-19 incidence in vaccinated volunteers against unvaccinated people, remains the best measure. Clinical trial investigators don't have other options until scientists can establish a clear biological measure that can predict whether a vaccine will protect against disease, Allende said.
However, she added the FDA is working on new measures. "We are engaged in several conversations to implement strategies to monitor and address the issue of variants that are circulating," Allende told committee members. — Jonathan Gardner
Maria Allende, a branch chief within the FDA's vaccine review division, began the meeting with a sobering statistic. Though COVID-19 cases, hospitalizations and deaths have all declined substantially, there were still over 400,000 cases in the U.S. over the week ending Feb. 24 and more than 2,000 deaths each day.
Those numbers are the lowest the U.S. has reported for months. But they're also far higher than what was reported for most of last year. It's a reminder of the urgent need for another vaccine, as well as for continued mitigation strategies. — Ben Fidler
Arnold Monto, an epidemiologist and professor at the University of Michigan, opened the meeting as chair of the 22-member advisory committee that will be reviewing J&J's vaccine today.
Most of the committee members are the same as those who reviewed Pfizer's and Moderna's vaccine in December. But there are a few changes. Sheldon Toubman, a Connecticut lawyer and consumer representative in past meetings, has been replaced by Jay Portnoy, a University of Missouri professor and allergist at Children's Mercy Hospital in Kansas City. Two other members from the Dec. 17 meeting on Moderna's vaccine have also been replaced.
In the morning, the FDA will review its emergency use authorization framework, while a CDC official will give an update on the epidemiology of new coronavirus variants. Another official, Tom Shimabukuro, will discuss safety data that's been collected since immunizations with Pfizer's and Moderna's vaccines began.
J&J will present just before lunch, which will be followed by an open public hearing and the FDA's presentation. Much of both presentations will go over documents released on Wednesday.
The most important part of the meeting comes at 3:10 pm ET, when the committee will begin its debate over whether to recommend use of J&J's shot. Panel members to watch include Archana Chatterjee, Michael Kurilla, A. Oveta Fuller and H. Cody Meissner, all of whom were more vocal in raising concerns and questions during the December votes on Pfizer's and Moderna's vaccines. — Ned Pagliarulo
J&J's shot uses a virus to shuttle a DNA sequence for the coronavirus's spike protein into the body, while Moderna's and Pfizer's rely on tiny lipid bubbles carrying messenger RNA. J&J's is given as a single dose, rather than a two-dose regimen. It's also easier to store and ship than the others.
All three offer near-complete protection against severe COVID-19, hospitalization or death — a significant finding now reported for several vaccines.
Beyond that result, it's harder to compare J&J's vaccine directly to the others. Moderna's and Pfizer's shots were nearly 95% effective at preventing COVID-19, but those results came late last year and were recorded before the spread of new variants that appear to weaken vaccine potency.
J&J's shot was 66% effective, but it was tested later and performed worse against the so-called B.1.351 variant, which originated in South Africa and has since spread to other countries, including the U.S. Testing also hasn't gone on long enough to determine whether one shot offers long-lasting protection.
What's more, J&J counted COVID-19 cases slightly differently than Moderna and Pfizer, adding a wrinkle to any direct comparison. — Ben Fidler
The FDA is widely expected to authorize J&J's vaccine soon after the meeting, potentially making the day's discussion less dramatic. But the virtual gathering is nonetheless a critical forum to discuss emerging pandemic issues, most notably coronavirus variants and how to combat them.
One high-ranking official from the Centers for Disease Control and Prevention will give a briefing later today on the variants that have recently spread across the globe. That discussion will come after a week in which the FDA released guidelines for updating vaccines to address new viral strains, and Moderna and Pfizer both progressed plans to test boosters or modified shots.
Experts will also get the most detailed look to date at the impact of the B.1.351 variant. J&J has the most efficacy data against B.1.351 of any vaccine developer, and its shot's protection against COVID-19 was clearly diminished by the variant. The vaccine seemed to still protect volunteers against severe disease comparably well regardless of variant, however. — Ben Fidler
Distribution of the two available coronavirus vaccines has ramped up considerably after a slow start, with some 46 million Americans, or about 14% of the population, having received at least one dose as of Wednesday, according to data from the Centers for Disease Control and Prevention. But supply remains a bottleneck, as most of the doses the U.S. preordered from Moderna and Pfizer won't be delivered until between April and July.
The imminent authorization of J&J's shot will help, though as with Moderna and Pfizer, only a fraction of the 100 million doses the U.S. ordered will be available right away. A J&J executive testifying before Congress this week said the company could deliver roughly 4 million doses upon FDA clearance, and 20 million by the end of March. J&J has promised to ship all 100 million doses by the end of June. — Ben Fidler