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Johnson & Johnson's COVID-19 one-dose vaccine candidate was 66% effective overall against moderate to severe COVID-19 in a multinational phase III trial, and 72% effective in the U.S. cohort, the company said on Friday.

Interim data showed 468 symptomatic cases of COVID-19 from 43,783 adult volunteers in the U.S., Latin America and South Africa, who comprised the phase 3 ENSEMBLE trial. The one-dose vaccine met its co-primary endpoints, which was protection against symptomatic COVID-19 at day 14 and day 28 following vaccination.

Notably, however, the primary outcome did not count mild COVID-19 cases, whereas the vaccines now in distribution from Pfizer/BioNTech and Moderna did while achieving efficacy rates close to 95%. The new trial had co-primary endpoints of moderate-severe illness assessed at 14 days and 28 days after dosing.

Specifically, J&J's defined moderate COVID as a positive PCR test plus at least one of the following: evidence of pneumonia, deep vein thrombosis, shortness of breath or abnormal blood oxygen saturation above 93%, or respiratory rate ≥20); or two or more systemic symptoms suggestive of COVID-19. Moderna and Pfizer, on the other hand, defined cases more liberally; a cough plus positive PCR test was enough to count toward their primary endpoints.

Criteria for severe COVID-19 in ENSEMBLE included "signs consistent with severe systemic illness, admission to an intensive care unit, respiratory failure, shock, organ failure or death, among other factors," as well as a positive PCR test, the company said.

There were no deaths in the vaccine group, and five deaths in the placebo group related to COVID-19, and 13 deaths in the placebo group and three deaths in the vaccine group overall.

The product, developed by Johnson & Johnson's Janssen unit, uses an adenoviral vector to deliver genetic material encoding coronavirus spike protein elements. It is stable for months at refrigerator temperatures. The company is also conducting another phase III trial called in which participants will receive two doses, about 2 months apart.

Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, which partially funded the trial, said in a media briefing that if there had not been vaccine candidates showing 94% and 95% efficacy, "one would've said this [72% efficacy] was an absolutely spectacular result."

For combined endpoints, protection in the U.S. was 72%, with 66% in Latin American countries and 57% in South Africa, where most cases were due to the South African variant.

Fauci emphasized that the vaccine reportedly showed 85% protection against severe disease, even in regions such as South Africa with variants, and said this had "important domestic and public health implications." Until now, he said, and until Thursday's news about Novavax, the effect of variants on vaccine protection had been mainly seen through in vitro studies.

"What we've learned now ... is antigenic variation has clinical consequences," he said. "Now we have real-world clinical consequences and see we're going to be challenged. It's really a wake-up call for us to be nimble and for us to adjust as this virus will continue ... as we get more ... immunological pressure."

Fauci stressed the importance of vaccinating the public as quickly as possible, as, "the best way to prevent further evolution of a virus is to prevent it from replicating."

Mathai Mammen, MD, PhD, of Johnson & Johnson, said the vaccine provided "100% protection against hospitalization and death" post-day 28 of vaccination. It also showed "continued, sustained holding of immunity at 28 days, and may get better with time." He added the vaccine showed protection across all age groups, comorbidities, races and ethnicities in the trial.

When asked if the vaccine prevented against asymptomatic disease, Mammen said they had been collecting blood samples to see how many people seroconverted and said "the total number of cases is small, but we're directionally pleased with what we see." He said the results would be shared in upcoming months.

The U.S. government purchased 100 million doses of vaccine from Johnson & Johnson to be delivered by the end of June, which committed to producing up to one billion doses this year.

Matt Hepburn, MD, the COVID-19 Response Vaccine Team Lead, said the U.S. government would be looking at how best to use this single-dose vaccine to "augment the current vaccination roll-out that we see" in this country.

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