Antibody combo of Tixagevimab and Cilgavimab effectively prevents COVID-19: NEJM
UK: Single dose of AZD7442 (Tixagevimab-Cilgavimab) is effective for COVID-19 prevention sans any evident safety concerns. Further administration of Monoclonal antibody combination tixagevimab-cilgavimab (Evusheld) maintained efficacy up to 6 months in high risk of COVID-19 patients, showed PROVENT trial.
The study has been published in the New England Journal of Medicine.
The study showed the incidences of symptomatic RT-PCR–positive SARS-CoV-2 infection and severe disease among infected participants to be lower in the AZD7442 group than in the placebo group, and there were no evident safety concerns.
The monoclonal-antibody combination AZD7442 is comprised of two monoclonal neutralizing antibodies, tixagevimab and cilgavimab that are derived from isolated B cells obtained from persons infected with SARS-CoV-2. They have an extended half-life and have been shown to have prophylactic and therapeutic effects in animal models. In humans, pharmacokinetic data indicate that AZD7442 has an extended half-life of approximately 90 days.
In the study, Myron J. Levin, and colleagues reported results from the ongoing, phase 3 PROVENT trial, which evaluated AZD7442 for the prevention of symptomatic and severe Covid-19 in adults.
The trial enrolled adults (≥18 years of age) who had an increased risk of an inadequate response to vaccination against coronavirus disease 2019 (Covid-19), an increased risk of exposure to SARS-CoV-2, or both. They were randomly assigned in a ratio of 2:1 to receive a single dose (two consecutive intramuscular injections, one containing tixagevimab and the other containing cilgavimab) of either 300 mg of AZD7442 or saline placebo. They were followed up to 183 days in the primary analysis.
The incidence of adverse events after a single dose of AZD7442 was the primary safety endpoint. The primary efficacy endpoint was symptomatic Covid-19 occurring after administration of AZD7442 or placebo and on or before day 183. SARS-CoV-2 infection was confirmed by means of reverse-transcriptase–polymerase-chain-reaction assay.
The study led to the following findings:
· A total of 5197 participants underwent randomization and received one dose of AZD7442 or placebo (3460 in the AZD7442 group and 1737 in the placebo group).
· The primary analysis was conducted after 30% of the participants had become aware of their randomized assignment.
· In total, 1221 of 3461 participants (35.3%) in the AZD7442 group and 593 of 1736 participants (34.2%) in the placebo group reported having at least one adverse event, most of which were mild or moderate in severity.
· Symptomatic Covid-19 occurred in 8 of 3441 participants (0.2%) in the AZD7442 group and in 17 of 1731 participants (1.0%) in the placebo group (relative risk reduction, 76.7%); extended follow-up at a median of 6 months showed a relative risk reduction of 82.8%.
· Five cases of severe or critical Covid-19 and two Covid-19–related deaths occurred, all in the placebo group.
To conclude, "the data reported here provide support for the use of AZD7442 as immunoprophylaxis to prevent Covid-19."
"Pharmacokinetic data showed AZD7442 persistence in serum for 6 months after administration, which resulted in SARS-CoV-2–neutralizing antibody titers that remained higher at days 8 and 29 than those reported in convalescent serum," the researchers wrote.
Reference:
Levin MJ, Ustianowski A, De Wit S, Launay O, Avila M, Templeton A, Yuan Y, Seegobin S, Ellery A, Levinson DJ, Ambery P, Arends RH, Beavon R, Dey K, Garbes P, Kelly EJ, Koh GCKW, Near KA, Padilla KW, Psachoulia K, Sharbaugh A, Streicher K, Pangalos MN, Esser MT; PROVENT Study Group. Intramuscular AZD7442 (Tixagevimab-Cilgavimab) for Prevention of Covid-19. N Engl J Med. 2022 Apr 20. doi: 10.1056/NEJMoa2116620. Epub ahead of print. PMID: 35443106.
