As expected, the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) looked favorably upon the latest COVID-19 entry: Ad26.COV2.S, a one-shot product that emerged from the same Johnson & Johnson (J&J) platform, AdVac, that let the firm devise an Ebola vaccine cleared in Europe last year.
Much discussion preceded the vote on a single question: “Based on the totality of scientific evidence available, do the benefits of [Ad26.COV2.S] outweigh its risks for use in individuals 18 years of age and older?” The result was unanimously yes, with 22 ballots. Jay Portnoy, acting consumer rep, is a professor of pediatrics at the University of Missouri Kansas City School of Medicine. “There’s an urgency to get this done,” he said. “We’re in a race [with] the virus mutating, new variants coming out that can cause further disease.” Patrick Moore, professor at the University of Pittsburgh Cancer Institute in Pittsburgh, said that “things are looking good” for now. “That could change tomorrow. My whole point is that this process, the [emergency use authorization, or EUA] process, does seem to have worked, despite my own personal concerns about it, say, six months ago.” Cody Meissner, professor of pediatrics at Tufts University School of Medicine in Boston, said officials should not rank the vaccines. “This falls under the purview of the CDC, the [Advisory Committee on Immunization Practices],” he said. “Hopefully, they will emphasize that there is no preference for one vaccine over another,” so that people will take whatever vaccine becomes available as soon as it does.
Through its Janssen Biotech unit, J&J is requesting an EUA that would let Ad26.COV2.S, an adenovirus serotype 26 vector encoding a full-length and stabilized SARS-CoV-2 spike protein, join mRNA vaccines from Moderna Inc. and Pfizer Inc./Biontech SE in the health care system’s needle box. New York-based Pfizer and Biontech, of Mainz, Germany, have gained EUA status for BNT-162b2. Cambridge, Mass.-based Moderna won the same for mRNA-1273.
With many people still not inoculated as variants of the virus loom, officials are scrambling to distribute injections. Ad26.COV2.S, packaged in a five-dose vial, requires no dilution and can be stored at normal refrigeration temperatures for up to three months, providing a logistical edge over the other two vaccines, though efficacy with the product is somewhat less. J&J has started late-stage trials to evaluate a two-dose regimen, with recruitment expected to finish in March.
In J&J’s trial called Ensemble, among all participants from different geographies – including those infected with an emerging variant – Janssen’s COVID-19 vaccine candidate was 66% effective overall in preventing moderate to severe COVID-19, 28 days after the shot. Both of the other vaccines have yielded 95% efficacy. Top-line safety and efficacy data disclosed Jan. 29 by J&J were based on 43,783 participants accruing 468 symptomatic cases of COVID-19. Ahead of the VRBPAC meeting, Cowen analyst Joshua Jennings said in a report that he was “unable to unearth any controversial disclosures in our review of the panel packets. The primary efficacy analysis met the prespecified success criteria, and we expect the panel to focus on the strong hospitalization (100% prevention after 28 days) and mortality (0%) benefits.”
During an especially substantive stretch of the virtual VRBPAC meeting, peppered with webcam malfunctions and can-you-hear-me exchanges, epidemiologist Adam MacNeil from the CDC described what’s known about the variants, thanks to genomics-enabled investigation. He also described what is not. “We have to acknowledge that only a small proportion of viruses are being sequenced,” he said, estimating the amount only as high as about 10%. “The reality is that we can have a certain degree of evidence, but we may not ever know the full situation in terms of what is going on with the virus.” He cited the inherent time lag between sample collection and results of sequencing, which makes for a slow diagnostic tool with limited clinical utility.
‘Serial formulations’ ahead?
“We know that current mitigation strategies work, and they work against variant viruses,” MacNeil said, urging better adherence with such measures as masking, social distancing and hand washing. More variants, maybe with increased transmissibility, will likely emerge. Several variants already are achieving broad global spread, with containment “thus far unsuccessful,” he said.
Eric Rubin, adjunct professor at Brigham and Women’s Hospital in Boston, who is also editor-in-chief of The New England Journal of Medicine, asked about tracking of the variants. “To find those, you’d have to be systematically sampling the escape mutants – and that means rather intensively – and have a representative sample of the population to compare that with. I wonder about both of those pieces. The 3,000, say, sequences we’re getting [per] week right now, do we know they’re representative?” MacNeil said samples are submitted by health jurisdictions in numbers based on their populations. “It does remain an ongoing challenge,” he said. “We can never hope to be perfectly representative, but I think we are getting relatively close.” The number of sequences done by commercial labs is increasing, too, he said.
Meanwhile, vaccine developers are busy as well. “In contrast to Moderna’s more aggressive (or at least, more public) effort to develop SARS-CoV-2 variant-specific vaccines, Biontech is taking a more measured approach,” SVB Leerink analyst Daina Graybosch said in a Feb. 25 report. She spoke with Biontech CEO Ugur Sahin about his firm’s strategy. “Last February, Biontech acknowledged their work on a vaccine for COVID-19, but the program was in its nascency,” she noted. “Now, after having successfully developed, manufactured, and delivered millions of doses of the first COVID-19 vaccine in record-setting time, the company faces different challenges,” as it figures out “how to manage this rapid growth and best deploy the substantial sums expected from [vaccine] sales.”
Sahin “expressed skepticism that in vitro evidence of decreased vaccine efficacy against variants [such as] B.1.351 would necessarily translate to decreased protection from disease,” Graybosch reported. “While acknowledging a three-fold reduction in neutralization titers with [the vaccine] against B.1.351, he said the magnitude of antibody response remains high and sufficient to provide protection.” Also, in his view, “testing of sera collected within weeks of vaccination may overestimate [the] impact, as affinity maturation could result in improved protection over time.”
SVB Leerink’s Mani Foroohar checked in with Moderna’s chief medical officer, Tal Zaks, exploring the prospect of COVID-19 boosters. The need for them, he said, “may depend on the type of variant affecting the population, along with which subpopulations are at risk in out-years.” In the future, said Zaks – who is leaving the company in September – “there is a need to further understand the type of variants circulating in the population, and whether certain variants are more prevalent, and if the dominant variant is consistently changing, suggesting [that] serial vaccine formulations could be necessary.” Moderna “continues to invest in sequencing of the positive COVID-19 cases from patients in [its] clinical trial, as genotyping will allow for examination and tracking of potential immune escape and breakthrough cases, leading to the ability to understand (re)infection drivers in real time,” he said.
Shares of J&J (NYSE:JNJ) closed $158.46, down $4.30.