FDA Staff Find Few Faults With J&J COVID Vaccine

 Johnson & Johnson's one-dose COVID-19 vaccine candidate seemed to meet criteria for emergency use authorization, according to FDA briefing documents released on Wednesday.

On Friday, Johnson & Johnson's vaccine, Ad26.COV2.S, which uses an adenovirus vector for SARS-CoV-2 genetic elements, will be reviewed by the FDA's Vaccines and Related Biological Products Advisory Committee (VRBPAC). This is the third COVID-19 vaccine candidate slated for review, as VRBPAC previously gave favorable recommendations to the Pfizer/BioNTech and Moderna vaccines, both of which were granted emergency authorization in December.

Similar to the previous two meetings, VRBPAC will decide whether, based on the totality of scientific evidence, the benefits of this vaccine outweigh the risks for adults ages 18 and older.

Based on the briefing documents, FDA technical staff found limited issues with the vaccine's efficacy or safety. Johnson & Johnson's phase III trial was dubbed "Study 3001," and included 43,783 participants in the U.S., Latin America, and South Africa randomized 1:1 to receive the active vaccine or placebo.

Notably, the co-primary endpoints of moderate to severe COVID-19 at 14 and 28 days following vaccination differed slightly from Pfizer and Moderna. Moderate COVID was defined 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 bpm; or two or more systemic symptoms suggestive of COVID-19. Moderna and Pfizer defined cases more liberally; a cough plus positive PCR test was enough to count toward the primary endpoints.

Topline data was released by the manufacturer and NIAID, which partially funded the trial, on Jan. 29, though it has yet to be published in a peer-reviewed journal. Data reviewed by FDA technical staff found 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.

Buried in the middle of page 38 was vaccine efficacy in the U.S., which was 74.4% at 14 days following vaccination and 72% at 28 days following vaccination.

Vaccine 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.

FDA technical staff noted that efficacy estimates were lower among adults ages 60 and older with comorbidities, though confidence intervals across subgroups "generally overlapped" and efficacy estimates in older participants with comorbidities increased with the number of cases in the analysis. Two hospitalizations in the vaccine group 14 days after vaccination occurred in participants older than age 60 with comorbidities.

The vaccine had lower efficacy in South Africa (52% after 14 days, and 64% after 28 days). Researchers sequenced 72% of the strains in primary efficacy analyses and found nearly all strains in South Africa were from the B.1.351 variant. There were no cases involving the Brazilian (P.1) or U.K. (B.1.1.7) variants in the trial.

Overall, the mean age of study participants was 51, while 55% were men and two-thirds were ages 18-59. About 59% were white, with 45% of Hispanic or Latino ethnicity, and 44% were from the U.S. About 40% had one or more comorbidities.

In terms of 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.

FDA technical staff analyzed imbalances in adverse events of clinical interest and concluded that a numerical imbalance in events of arthritis and peripheral neuropathy potentially represented vaccine reactogenicity. An imbalance in urticaria (five events in the vaccine group vs one in the placebo group within 7 days of vaccination) was determined to be "possibly" related to the vaccine based on temporal association and biologic plausibility.

However, there was insufficient evidence to determine casual relationships to the vaccine for vaccine versus placebo imbalances in thromboembolic events (15 vs 0, respectively) and tinnitus (6 vs 0), FDA technical staff said.

Three of seven serious adverse events in the vaccine group were considered vaccine-related, including one hypersensitivity reaction not classified as anaphylaxis, one severe injection site pain, and one severe systemic reactogenicity.

As of Jan. 22, 19 deaths were reported -- three in the vaccine group and 16 in the placebo group. Two deaths in the vaccine group were secondary to respiratory infections unrelated to COVID-19, and one was in a participant with HIV. The third died of unknown causes after waking up with shortness of breath.

Johnson & Johnson included a plan for continuing follow-up, which had been an issue at the other two COVID-19 vaccine advisory committees, allowing all participants who received placebo to receive the vaccine when permissible but remain in the trial.

There are currently insufficient data to make determinations about safety in children, pregnant women, and immunocompromised individuals, FDA technical staff noted.

https://www.medpagetoday.com/infectiousdisease/covid19/91343