• Myron J Levin, Andrew Ustianowski, Stéphane De Wit, Odile Launay, Miles Avila, Alison Templeton, Yuan Yuan, Seth Seegobin, Adam Ellery, Dennis J Levinson, Philip Ambery, Rosalinda H Arends, Rohini Beavon, Kanika Dey, Pedro Garbes, Elizabeth J Kelly, KohGavin C K WGCKWFrom the University of Colorado School of Medicine, Aurora (M.J.L.); North Manchester General Hospital, Manchester (A.U.), Biometrics (A.T., S.S.) and Clinical Development (R.B., G.C.K.W.K.), Vaccines and Immune Therapies, Biopharmaceuti, Karen A Near, Kelly W Padilla, Konstantina Psachoulia, Audrey Sharbaugh, Katie Streicher, Menelas N Pangalos, Mark T Esser, and PROVENT Study Group.
• From the University of Colorado School of Medicine, Aurora (M.J.L.); North Manchester General Hospital, Manchester (A.U.), Biometrics (A.T., S.S.) and Clinical Development (R.B., G.C.K.W.K.), Vaccines and Immune Therapies, Biopharmaceuticals Research and Development (M.N.P.), AstraZeneca, Cambridge, and Mounts Bay Medical, Penzance (A.E.) - all in the United Kingdom; the Division of Infectious Diseases, Saint-Pierre University Hospital, Université Libre de Bruxelles, Brussels (S.D.W.); Université de Paris, INSERM French Clinical Research Infrastructure Network, Innovative Clinical Research Network in Vaccinology, Assistance Publique-Hôpitaux de Paris, Paris (O.L.); Chicago Clinical Research Institute, Chicago (D.J.L.); Clinical Development, Late-Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals Research and Development, AstraZeneca, Gothenburg, Sweden (P.A.); Clinical Pharmacology and Quantitative Pharmacology (R.H.A.), Clinical Development (K.D., P.G., K.A.N., K.P.), Biometrics (M.A., Y.Y.), Translational Medicine (E.J.K., K.S.), and Vaccines and Immune Therapies (M.T.E.), Biopharmaceuticals Research and Development, AstraZeneca, Gaithersburg, MD; and Clinical Development, Vaccines and Immune Therapies, Biopharmaceuticals Research and Development, AstraZeneca, Durham, NC (K.W.P., A.S.).
• N. Engl. J. Med. 2022 Jun 9; 386 (23): 218822002188-2200.

BackgroundThe monoclonal-antibody combination AZD7442 is composed of tixagevimab and cilgavimab, two neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that have an extended half-life and have been shown to have prophylactic and therapeutic effects in animal models. Pharmacokinetic data in humans indicate that AZD7442 has an extended half-life of approximately 90 days.MethodsIn an ongoing phase 3 trial, we 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. Participants were randomly assigned in a 2:1 ratio 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, and they were followed for up to 183 days in the primary analysis. The primary safety end point was the incidence of adverse events after a single dose of AZD7442. The primary efficacy end point was symptomatic Covid-19 (SARS-CoV-2 infection confirmed by means of reverse-transcriptase-polymerase-chain-reaction assay) occurring after administration of AZD7442 or placebo and on or before day 183.ResultsA 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%; 95% confidence interval [CI], 46.0 to 90.0; P<0.001); extended follow-up at a median of 6 months showed a relative risk reduction of 82.8% (95% CI, 65.8 to 91.4). Five cases of severe or critical Covid-19 and two Covid-19-related deaths occurred, all in the placebo group.ConclusionsA single dose of AZD7442 had efficacy for the prevention of Covid-19, without evident safety concerns. (Funded by AstraZeneca and the U.S. government; PROVENT ClinicalTrials.gov number, NCT04625725.).Copyright © 2022 Massachusetts Medical Society.

31 keywords...

hide…