Intramuscular AZD7442 (Tixagevimab–Cilgavimab) for Prevention of Covid-19
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, Gavin C K W Koh, Karen A Near, Kelly W Padilla, Konstantina Psachoulia, Audrey Sharbaugh, Katie Streicher, Menelas N Pangalos, Mark T Esser
New England Journal of Medicine, doi:10.1056/nejmoa2116620
BACKGROUND The 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.
METHODS In 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 reversetranscriptase-polymerase-chain-reaction assay) occurring after administration of AZD7442 or placebo and on or before day 183.
RESULTS 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%; 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-19related deaths occurred, all in the placebo group.
CONCLUSIONS A 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.
SARS-CoV-2 Variants Viral genotypic data collected at illness visits were available for 7 of 11 symptomatic participants in the AZD7442 group and 13 of 31 symptomatic participants in the placebo group. Eleven of these participants were infected with a SARS-CoV-2 vari- A data sharing statement provided by the authors is available with the full text of this article at NEJM.org. We thank the trial participants, their families, and all investigators involved in this trial; the members of the adjudication committee, who assessed deaths that occurred during the trial:
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{ 'given': 'Karen A.',
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{ 'given': 'Audrey',
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'G.C.K.W.K.), Vaccines and Immune Therapies, Biopharmaceuticals '
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'Mounts Bay Medical, Penzance (A.E.) — all in the United Kingdom; '
'the Division of Infectious Diseases, Saint-Pierre University '
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'Université de...'}]},
{ 'given': 'Menelas N.',
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'(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...'}]},
{ 'given': 'Mark T.',
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'G.C.K.W.K.), Vaccines and Immune Therapies, Biopharmaceuticals '
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'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.); '
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'URL': 'http://dx.doi.org/10.1056/nejmoa2116620',
'relation': {},
'ISSN': ['0028-4793', '1533-4406'],
'issn-type': [{'value': '0028-4793', 'type': 'print'}, {'value': '1533-4406', 'type': 'electronic'}],
'subject': ['General Medicine'],
'published': {'date-parts': [[2022, 4, 20]]}}
