Johnson & Johnson Announces Real-World Evidence and Phase 3 Data Confirming Strong and Durable Protection of Single-Dose COVID-19 Vaccine in the U.S.

New Data Indicate Booster Doses Enhance Protection

In the United States, following the first vaccination

Booster vaccination at two months provided 94% protection.

Antibody Levels Increase Fourfold Two Months After Booster Vaccination

Antibody levels can increase 12-fold when a booster dose is administered at six months.

On September 21, Johnson & Johnson announced the latest data, further confirming the robust and durable protection provided by its COVID-19 vaccine. The updated data also demonstrate that administering a booster dose of the Johnson & Johnson vaccine can further enhance protection against COVID-19. When administered as a booster, the vaccine's safety profile remained consistent and was generally well-tolerated.

“Our extensive real-world evidence and Phase 3 studies confirm that the Johnson & Johnson single-dose vaccine provides robust and durable protection against COVID-19-related hospitalizations. Furthermore, our Phase 3 trial data further demonstrate the vaccine's protection against COVID-19-related deaths,” said Dr. Mathai Mammen, Global Head of R&D at Janssen, Johnson & Johnson’s pharmaceutical company. “Our single-dose vaccine elicits a robust immune response and durable immune memory. Meanwhile, receiving a Johnson & Johnson COVID-19 vaccine booster can further enhance protection against COVID-19.”

Dr. Paul Stoffels, Executive Vice Chairman of the Executive Committee and Chief Scientific Officer of Johnson & Johnson, stated: “Given the ongoing spread of COVID-19, it is imperative to prevent the resulting hospitalizations and deaths in as many people as possible. A single-dose COVID-19 vaccine that is easy to use, distribute, and administer, and that provides robust and long-lasting protection, is critical to vaccinating the global population. At the same time, the evidence we now have indicates that a booster dose can further enhance protection against COVID-19 and is expected to significantly extend the duration of that protection.”

The company has provided the existing data to the U.S. Food and Drug Administration (FDA) and plans to submit these data to other regulatory authorities worldwide, the World Health Organization (WHO), and National Immunization Technical Advisory Groups (NITAGs) in various countries, as necessary, to inform decision-making for local vaccination strategies.

Data overview is as follows:

Johnson & Johnson's single-dose vaccine has shown in the real world

Strong and Long-Lasting Protection

The largest real-world evidence study of a COVID-19 vaccine reported in the United States to date indicates that the vaccine maintained a consistent effectiveness of 79% (confidence interval, 77%–80%) against COVID-19-related infection and 81% (confidence interval, 79%–84%) against COVID-19-related hospitalization. There was no evidence that effectiveness waned over the course of the study, including during the period when the Delta variant became the dominant strain in the United States. No sequencing data are currently available for analysis. From March through late July 2021, the study included 390,000 recipients of the Johnson & Johnson COVID-19 vaccine and approximately 1.52 million unvaccinated individuals matched by age, sex, calendar time, 3-digit ZIP code, and comorbidities and predictive factors for COVID-19 severity.

These data are consistent with the data from the Phase 3 ENSEMBLE trial, in which robust protection against severe/critical disease and death was observed at least 28 days after the final vaccination:

- Across all age cohorts and all countries included in this study, the overall efficacy against severe/critical COVID-19 was 75% (confidence interval, 65%-82%).

- In the United States, the efficacy against severe/critical COVID-19 was 74% (confidence interval, 39%–91%); the efficacy against hospitalization was 89% (confidence interval, 24%–100%); and the efficacy against COVID-19-related death was 83% (confidence interval, 41%–97%).

In the United States, administration of a booster dose at 2 months played a role in

94% efficacy against COVID-19

The Phase 3 ENSEMBLE2 study showed that a second dose of the Johnson & Johnson COVID-19 vaccine administered 56 days after the first dose may provide:

- 100% efficacy against severe/critical COVID-19 (confidence interval, 33%–100%) – at least 14 days after completion of vaccination.

- Globally, demonstrates 75% efficacy against symptomatic (moderate to severe/critical) COVID-19 (confidence interval: 55%–87%).

- In the United States, it demonstrated 94% efficacy against symptomatic (moderate-to-severe/critical) COVID-19 (confidence interval, 58%–100%).

Two months after the initial vaccination, administration of a Johnson & Johnson COVID-19 vaccine booster resulted in antibody levels 4- to 6-fold higher than those observed following a single-dose vaccination.

Antibody levels increased 12-fold at 6 months following booster vaccination.

Six months after the initial dose, administration of a Johnson & Johnson COVID-19 vaccine booster resulted in a ninefold increase in antibody levels at one week post-booster, with levels continuing to rise to 12-fold at four weeks post-booster. All increases were independent of age.

The Johnson & Johnson single-dose COVID-19 vaccine was developed by Janssen Pharmaceuticals, Inc., a subsidiary of Johnson & Johnson. The vaccine received Emergency Use Authorization (EUA) in the United States on February 27, 2021, and Conditional Marketing Authorization (CMA) from the European Commission on March 11, 2021. The World Health Organization (WHO) added the vaccine to its Emergency Use Listing on March 12, 2021, and the company received interim recommendations from the WHO Strategic Advisory Group of Experts on Immunization (SAGE) on March 17, 2021. The Johnson & Johnson COVID-19 vaccine has since been authorized in additional countries worldwide, and regulatory submissions are currently underway.

-Supplementary Notes-

Real-World Evidence Study

In the largest real-world vaccine effectiveness (VE) evidence study to date conducted among recipients of Johnson & Johnson’s single-dose COVID-19 vaccine in the United States, the Janssen Research & Development Data Science team, Harvard University, and Aetion utilized the HealthVerity database, which comprises longitudinal, de-identified patient-level data representative of the US population. This study compared approximately 390,000 individuals who received the company’s single-dose COVID-19 vaccine with approximately 1,520,000 unvaccinated individuals, with the two cohorts matched on age, sex, calendar time, three-digit ZIP codes, comorbidities, and predictors of COVID-19 severity.

This study employed a longitudinal cohort design and utilized a robust propensity score matching method to create a control cohort for evaluating real-world VE. All analyses were conducted using the Aetion Evidence Platform, a scientifically validated software also utilized by regulatory agencies, payers, and health technology assessment organizations to evaluate the safety, effectiveness, and value of medical technologies. All data transformations from the original dataset were retained to ensure complete reproducibility, and an audit trail was provided, including quality checks on the data acquisition process.

In real-world data from the United States, the Johnson & Johnson single-dose COVID-19 vaccine showed a vaccine effectiveness (VE) of 81% against COVID-19-related hospitalization (confidence interval, 79%–84%) and 79% against COVID-19-related infection (confidence interval, 77%–80%) (VE was adjusted to account for misclassification of vaccination status due to insufficient recording of actual vaccination status in healthcare claims data). The unadjusted VE against COVID-19-related infection was 69% (confidence interval, 67%–71%); the VE against COVID-19-related hospitalization was 73% (confidence interval, 69%–76%).

The Johnson & Johnson single-dose COVID-19 vaccine demonstrated a VE of 86% (confidence interval, 83%-89%) against COVID-19-related hospitalization in individuals under 60 years of age, and 78% (confidence interval, 74%-81%) in those aged 60 years and older. For COVID-19 infection, the VE was 81% (confidence interval, 79%-82%) in the population under 60 years of age, and 75% (confidence interval, 73%-78%) in those aged 60 years and older. These results are consistent with those observed in the ENSEMBLE study.

ENSEMBLE1 Study

The Phase 3 ENSEMBLE study is a randomized, double-blind, placebo-controlled clinical trial designed to evaluate the safety and efficacy of a single-dose vaccine versus placebo in adults aged 18 years and older.

The ENSEMBLE study is designed to evaluate the safety and efficacy of the Johnson & Johnson candidate vaccine in preventing moderate to severe/critical COVID-19 disease, with efficacy assessed at ≥14 days and ≥28 days post-vaccination as co-primary endpoints.

In the Phase 3 ENSEMBLE study, at least 28 days after vaccination, the Johnson & Johnson single-dose COVID-19 vaccine demonstrated robust and durable overall efficacy against severe/critical COVID-19 across all age cohorts and all countries/regions included in the study (75%; confidence interval: 65%–82%; vaccine group = 46, placebo group = 176). While efficacy against severe/critical COVID-19 remained very high against the originally circulating SARS-CoV-2 reference strain (93%; confidence interval: 54%–99%; vaccine group = 1, placebo group = 14), it was slightly reduced against variant strains (72%; confidence interval: 56%–82%; vaccine group = 27, placebo group = 93).

The efficacy of the single-dose vaccine against moderate to severe/critical infection was 53% (confidence interval: 47%-58%; vaccine group = 433 cases, placebo group = 883 cases), and against the reference strain was 58% (confidence interval: 35%-74%; vaccine group = 30 cases, placebo group = 69 cases). In the ENSEMBLE trial, the efficacy against COVID-19-related hospitalization was 76% (confidence interval: 54%-88%; vaccine group = 16 cases, placebo group = 64 cases), and against COVID-19-related death was 83% (confidence interval: 41%-97%; vaccine group = 3 cases, placebo group = 17 cases).

In the United States, the ENSEMBLE trial demonstrated that, 28 days after vaccination, vaccine efficacy against moderate/severe or critical COVID-19 infection was 70% (confidence interval: 61%–77%; vaccine group = 77 cases, placebo group n = 239 cases), efficacy against severe/critical infection was 74% (confidence interval: 39%–91%; vaccine group = 7 cases, placebo group = 26 cases), and efficacy against hospitalization was 89% (confidence interval: 24%–100%; vaccine group = 1 case, placebo group = 9 cases).

The median follow-up duration in the ENSEMBLE study was 4 months, with 23% of participants followed for more than 6 months.

Compared with the Phase 1/2 data, the vaccine was generally well tolerated in all participants, with fewer local and systemic adverse reactions.

ENSEMBLE was jointly initiated under Other Transaction Agreement HHSO100201700018C by the Biomedical Advanced Research and Development Authority (BARDA) (within the Office of the Assistant Secretary for Preparedness and Response at the U.S. Department of Health and Human Services (HHS)) and the National Institute of Allergy and Infectious Diseases (NIAID) (within the National Institutes of Health (NIH) at HHS).

Complete data will be submitted for publication within the next few months.

ENSEMBLE2 Study

The Phase 3 ENSEMBLE 2 study is a randomized, double-blind, placebo-controlled clinical trial designed to evaluate the safety and efficacy of a two-dose vaccine regimen with a 56-day dosing interval compared with placebo in adults aged 18 years and older, with or without comorbidities that increase the risk of severe COVID-19.

This study aimed to evaluate the efficacy following the first and second doses of the investigational vaccine, to assess its efficacy in preventing viral infection and the potential incremental benefit during the period of protection conferred by the second dose. In the Phase 3 ENSEMBLE 2 study, solicited and unsolicited adverse events following the second vaccination were similar to those observed in the single-dose study.

Compared with the single-dose results, ENSEMBLE 2 also demonstrated that at least 14 days after the second dose and prior to unblinding, the efficacy of the two-dose regimen against moderate to severe/critical COVID-19 increased to 75% (confidence interval: 55%–87%; vaccine group = 14 cases, placebo group = 52 cases), and efficacy against severe/critical COVID-19 was 100% (confidence interval: 33%–100%; vaccine group = 0 cases, placebo group = 8 cases). In the United States, efficacy against moderate to severe/critical COVID-19 was 94% (confidence interval: 58%–100%; vaccine group = 1 case, placebo group = 14 cases).

In the ENSEMBLE2 study, the median follow-up time was 36 days from the second dose, with 29% of subjects followed for at least 2 months after the second dose.

The vaccine was generally well tolerated when administered as a second dose or booster dose.

The complete data will be submitted for publication within the next few months.

Responsible Editor: Sanqi

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