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An FDA advisory committee voted unanimously Friday to recommend the Johnson & Johnson COVID-19 vaccine (Ad26.COV2.S) for use in adults 18 and older.

Based on the totality of scientific evidence available, the FDA's Vaccines and Related Biological Products Advisory Committee (VRBPAC) voted 22-0 that benefits of the vaccine "outweigh its risks for use in individuals 18 years of age and older," so the vaccine should qualify for FDA emergency use authorization (EUA). Most members focused on the importance of getting out another vaccine against the virus, given the rising number of variants threatening to curtail progress against the pandemic.

"This was a relatively easy call," said Eric Rubin, MD, PhD, of Harvard T.H. Chan School of Public Health in Boston, and editor-in-chief of the New England Journal of Medicine. "It's a bit challenging to understand how to use it clinically right now, but it still has a place."

Part of the confusion may have arisen from the presentation from Johnson & Johnson's Janssen Biotech division, which mentioned a two-dose study currently in progress.

VRBPAC acting chair Arnold Monto, MD, of the University of Michigan, implied that was a question for CDC's Advisory Committee on Immunization Practices, "especially if the two-dose formulation ... appears to be more efficacious." The FDA panel could only review the vaccine as a one-dose regimen at the Friday meeting, since that was what Johnson & Johnson had applied for.

FDA staff confirmed if an EUA was issued, and two doses subsequently prove to be more effective, the authorization could be amended.

Data supporting the current EUA application (the same as presented in pre-meeting briefing documents) were primarily from the phase III multi-national randomized, placebo-controlled trial dubbed ENSEMBLE by Johnson and Johnson, and sponsored in part by the National Institute of Allergy and Infectious Diseases. They showed 66.9% efficacy (95% CI 59.0%-73.4%) against moderate to severe COVID-19 at 14 days and 66.1% (95% CI 55.0-74.8%) at 28 days following vaccination. Vaccine efficacy in the U.S., which was 74.4% at 14 days following vaccination and 72% at 28 days following vaccination.

While the vaccine was mostly effective across demographic groups, FDA technical staff noted efficacy was lower among adults 60 and older with comorbidities versus healthier seniors. The two medically attended COVID-19 cases in the vaccine group were among older adults with comorbidities.

Peter Marks, MD, PhD, director of FDA's Center for Biologics Evaluation and Research, jumped into the discussion, asking whether the committee was comfortable with the reduced efficacy in that group, as "people may be looking at that with a lot of scrutiny." However, panel members demurred, appearing satisfied with the explanation that the follow-up period was shorter for those participants and as more cases accrued, the product's efficacy for that subgroup would become clearer.

Another issue for the committee was how the manufacturer defined moderate to severe COVID-19, with David Kim, MD, an HHS official, taking up the issue initially raised in the open public hearing. He pointed out that the manufacturer defined "moderate" COVID-19 as two symptoms plus a positive PCR test, with "mild" COVID as one symptom plus a positive PCR test, leading to "a total lack of mild COVID cases in the study."

Kim said the manufacturer needed to be "consistent" with definitions currently used by FDA, CDC and the other two vaccine manufacturers, and state their claim of 67% vaccine effectiveness "applies to symptomatic COVID."

Efficacy against severe COVID-19 for the entire cohort was 76.7% (95% CI 54.6%-89.1%) 14 days after vaccination and 85.4% (95% CI 54.2%-96.9%) at least 28 days after vaccination. A post-hoc analysis found two COVID-related hospitalizations in the vaccine group and 29 in the placebo group after 14 days, with 0 and 16 cases after 28 days, respectively.

Despite lower efficacy than the 95% boasted by Pfizer and Moderna, committee members wanted to be clear that one vaccine was not better than the other. In fact, this vaccine offered its own advantages, with Ofer Levy, MD, PhD, of Boston Children's Hospital, noting that the 4º C storage temperature makes it a practical choice for a variety of locales, including rural areas and globally.

Experience in children with Ad26 adenovirus platforms for other vaccines, such as for Ebola, could aid in bringing a pediatric indication for J&J's COVID vaccine, Levy added.

Examining safety, injection site pain was the most common local adverse reaction in the vaccine group (49%), while headache (39%) and fatigue (38%) were the most common systemic reactions. As with other vaccines, these were reported more frequently by younger participants.

While cases of confirmed anaphylaxis were not reported in the briefing documents, Janssen Biotech staff said during the meeting that two cases of severe allergic reaction had occurred in the past week during an ongoing clinical trial in South Africa, including one case of anaphylaxis. Those were still rare events, they stressed.

The FDA does not have to follow the advice of its advisory committees, but it often does.

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