Preprint data from a real-world evidence assessment, as well as preliminary reports from a 2-dose trial, support the company's pursuit for FDA authorization of a second COVID-19 vaccine dose.
Johnson & Johnson announced to-be-published phase 3 data from a real-world evidence trial showing their single-dose adenovirus-based COVID-19 vaccine Ad26.COV2.S was associated with 79% overall efficacy for the prevention of COVID-19 and 81% effective for the prevention of hospitalizations associated with the virus.
The new data from the company’s pivotal ENSEMBLE trial program also included data from ENSEMBLE 2, an assessment of a two-dose regimen of Ad26.COV2.S. A booster dose provided 56 days after the first dose was associated with a 94% efficacy in preventing symptomatic COVID-19 in the US, and 75% efficacy worldwide.
The company is now seeking US Food and Drug Administration (FDA) authorization of their booster dose regimen on the basis of this data, which has yet to be peer-reviewed.
In the preprint data from Johnson & Johnson’s cohort assessment of nearly 400,000 participants vaccinated with Ad26.COV2.S, investigators sought to observe the single-dose vaccine’s effectiveness in preventing COVID-19 and related hospitalizations in US clinical practice. They additionally wanted to observe its duration of protection over a longer, real-world observation, as well as its efficacy in preventing infection via more transmissible Delta variants.
Trial participants were newly vaccinated adults aged ≥18 years old, matched with up to 10 unvaccinated persons with similar demographics and COVID-19 risk factors. Vaccine effectiveness was estimated for observed COVID-19 infections and related hospitalizations, and was stratified by age, immunocompromised status, calendar time, and regions/states with greater incidence of the circulating Delta variant.
The trial population included 390,517 vaccinated and 1,524,153 unvaccinated individuals.
Estimated vaccine effectiveness was 79% (95% CI, 77 – 80) for COVID-19 and 81% (95% CI, 79 – 84) for COVID-19 hospitalizations. An assessment of calendar months from March – July 2021 showed overall vaccine effectiveness did not “meaningfully” vary over time:
Investigators additionally observed a greater vaccine effectiveness in persons aged <50 years (83%; 95% CI, 81 – 85), and a lower effectiveness in immunocompromised patients (64%; 95% CI, 57 – 70).
Among participants in states with high incidence of Delta variant infection, COVID-19 prevalence was greater among both vaccinated and unvaccinated cohorts. Investigators observed, however, an overall vaccine effectiveness of 79% (95% CI, 75 – 83) and 78% effectiveness versus hospitalization (95% CI, 73 – 82) in these states during June and July—the observed months when Delta variant incidence was at its greatest.
That said, this estimated data does not entail sequence-specific information, meaning there is no specific certainty of the vaccine effectiveness of Ad.COV2.S in preventing Delta variant-driven infection.
Nonetheless, investigators concluded the population-based US data demonstrates the “high and stable effectiveness” of the single-dose COVID-19 vaccine across both high-risk patient subpopulations, as well as residents in areas more adversely affected by the Delta variant.
“As the COVID-19 pandemic continues and variants evolve the observed effectiveness may change in the future as new variants emerge,” they concluded. “Our data and data to be generated over the coming months using this system of claims data contribute important and otherwise unattainable evidence to policymakers, physicians, and patients.”
The phase 3 ENSEMBLE 2 trial is a randomized, double-blind, placebo-controlled clinical trial assessing the efficacy and safety of 2-dose Ad26.COV2.S regimen administered at a 56-day interval, versus placebo among an international population of adults with varying risk for severe COVID-19.
Median follow-up in the trial, according to Johnson & Johnson, was 36 days since the second dose administration; just 29% of trial participants had ≥2 months of follow-up data after receiving the investigative booster dose.
Investigators observed 100% vaccine effectiveness (95% CI, 33 – 100) against severe or critical COVID-19 in ≥14 days post-booster dose. They additionally observed 75% overall effectiveness (95% CI, 55 – 87) versus symptomatic COVID-19 in patients globally, and 94% overall effectiveness (95% CI, 58 – 100) in US patients.
The company stated that a booster dose of Ad26.COV2.S was associated with a 4- to 6-fold increase in antibody titers versus a lone single-dose administration at 2 months. At 6 months, the booster dose was associated with a 12-fold increase in antibodies.
Johnson & Johnson intend to submit the full ENSEMBLE 2 study data for publication in the coming months.
In a statement accompanying the reported data, Paul Stoffels, MD, Johnson & Johnson Vice Chairman of the Executive Committee and Chief Scientific Officer, called it “critical” to prioritize prevention of hospitalization and death during the continued COVID-19 pandemic.
“A single-shot COVID-19 vaccine that is easy to use, distribute and administer, and that provides strong and long-lasting protection is crucial to vaccinating the global population,” Stoffels said. “At the same time, we now have generated evidence that a booster shot further increases protection against COVID-19 and is expected to extend the duration of protection significantly.”