The FDA briefing document says the vaccine has ‘a favorable safety profile with no specific safety concerns identified that would preclude issuance of an EUA’.
In support of its EUA request, submitted on February 4 and due to be assessed by the vacines committee tomorrow, J&J has provided the FDA with safety and efficacy data from an ongoing multi-national Phase 3 randomized, double-blind and placebo-controlled trial of Ad26.COV2.S in around 40,000 participants.
The candidate is a replication-incompetent adenovirus type 26 (Ad26)- vectored vaccine encoding a stabilized variant of the SARS-CoV-2 S protein, to prevent COVID-19 in individuals 18 years of age and older. The Ad26.COV2.S vaccine is administered as a single intramuscular injection of 5×1010 vp.
The vaccine is based on Janssen’s Ad26 vector platform, which is already used with other vaccines.
“Clinical experience with the Ad26 platform consists of the Ad26.ZEBOV/MVA-BN-Filo Ebola vaccine regimen (approved by the European Medicines Agency on July 1, 2020) and investigational vaccines against Zika, filovirus, HIV, HPV, malaria, and respiratory syncytial virus,” notes the FDA in a briefing document for tomorrow’s meeting. “As of 31 December 2020, Ad26-based vaccines have been used to vaccinate 193,831 participants in clinical studies and vaccination programs. Overall, these vaccines have been shown to have an acceptable clinical safety profile to date.”
The FDA has assessed safety data from the COVID-19 vaccine's clinical trials up to January 22, 2021, covering 43,783 participants with a 2-month median follow-up. “The analysis supported a favorable safety profile with no specific safety concerns identified that would preclude issuance of an EUA,” says the FDA.
J&J's Phase 3 study has reported the candidate has 66% efficacy in preventing moderate to severe COVID-19.
The Phase 3 study reported 193 cases of COVID-19 in the placebo group 28 days after administration; and 66 in the vaccinated group.
As of February 5, 2021, there were seven COVID-19 related deaths in the study in the placebo group and no COVID-19 related deaths in the vaccine group.
“In general, vaccine efficacy among the subgroups (age, comorbidity, race, ethnicity) appears to be similar to the vaccine efficacy in the overall study population,” notes the FDA.
“The vaccine is administered as a single dose, which provides operational benefits to mass vaccination campaigns.”
The vaccine has also demonstrated protection against multiple virus variants, including the South Africa B.1.351 lineage (15% of the study’s participants were based in South Africa).
“To explore the possible impact of circulation of variant strains on vaccine efficacy, a subgroup analysis of vaccine efficacy against moderate to severe/critical and severe/critical COVID-19 was done for the United States, South Africa, and Brazil," notes the FDA.
"There was a lower efficacy against moderate to severe/critical disease endpoints observed in South Africa [52.0% (95% CI 30.3, 67.4) and 64.0% (95% CI 41.2, 78.7) starting 14 days and 28 days after vaccination, respectively] compared to the United States (74.4% (65.0, 81.6) and 72.0% (58.2, 81.7) starting 14 days and 28 days after vaccination, respectively), but vaccine efficacy against severe/critical COVID-19 at the two timepoints were similarly high in all 3 countries.”
The vaccine is supplied as a multidose vial (5 doses) containing a refrigerated suspension with a shelf life of 3 months when stored at 2º to 8º C.
Pregnancy study to follow
J&J will conduct long-term follow-up of participants in the ongoing clinical trials. It has also submitted a protocol to the FDA for a multi-country study of the vaccine in pregnant women.
While the Phase 3 trial excluded women who were pregnant or planning to become pregnant, two pregnancies in the vaccine group are ongoing.
“A combined developmental and perinatal/postnatal reproductive toxicity study of Ad26.COV2.S in rabbits was submitted to FDA on January 19, 2021,” notes the FDA. “Our review of this study concluded that Ad26.COV.S given prior to mating and during gestation periods at dose of 1x1011 vp (2 times the human dose) did not have any adverse effects on female reproduction, fetal/embryonal development, or postnatal development.”
South Africa has already started rolling out the vaccine to health workers, after the country's regulator approved the vaccine under a Phase 3b trial program.
J&J has also submitted an application for Conditional Marketing Authorisation in Europe.