Evusheld protects against COVID-19 in at-risk adults
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A single dose of Evusheld appears effective at preventing COVID-19 infection, without notable safety concerns, in patients at risk for infection or vaccine nonresponse, according to data published in the New England Journal of Medicine.
“AZD7442 has been shown to neutralize SARS-CoV-2 and its variants of concern in vitro and has prophylactic and therapeutic effects in nonhuman primates,” Myron J. Levin, MD, of the University of Colorado School of Medicine in Aurora, and co-authors wrote. “In a phase 1 study, intramuscular administration of 300 mg of AZD7442 provided higher SARS-CoV-2 serum neutralizing titers than those associated with convalescent serum.”
To examine efficacy and safety of a single dose of AZD7442 (Evusheld, AstraZeneca), consisting of two consecutive intramuscular injections — tixagevimab and cilgavimab — Levin and colleagues conducted the PROVENT trial, an ongoing, double-blind, parallel-group, randomized, placebo-controlled, multicenter study. Patients were eligible to participate in the trial if they were aged 18 years or older and had an increased chance of disease exposure or of mounting an “inadequate” response to COVID-19 vaccination, or both.
Participants also were required to demonstrate a negative point-of-care SARS-CoV-2 serologic test at screening. Patients were excluded from the study if they had a history of SARS-CoV-2 infection, a positive test result at screening, if they previously received a vaccine or other therapy intended to prevent infection, or if they had an allergy to the drug in question.
The primary safety endpoint was the presence and rate of adverse events following Evusheld administration, compared with placebo. Researchers investigated adverse events, serious adverse events, medically attended adverse events and adverse events of special interest. Meanwhile, the primary efficacy endpoint was the first appearance of symptomatic disease, as confirmed by a reverse-transcriptase–polymerase-chain-reaction test, following administration and before day 183.
A qualifying event was established if patients presented with qualifying symptoms and had a positive test between 5 days before and 10 days after symptoms began.
A total of 5,197 participants were randomized. Of those, 3,460 received the AZD7442 dose and 1,737 received placebo. According to the researchers, 1,221 patients treated with the AZD7442 dose (35.3%) and 593 who received placebo (34.2%) reported at least one adverse event, most of which were characterized as mild or moderate. Meanwhile, eight participants who received AZD7442 (0.2%) and 17 in the placebo group (1%) developed symptomatic COVID-19.
The drug demonstrated a relative risk reduction of 76.5% (95% CI, 46-90), according to the researchers. Extended follow-up increased relative risk reduction to 82.8% (95% CI, 65.8-91.4), they added. There were five cases of “severe” or “critical” COVID-19 and two COVID-19-related deaths, all of which were in the placebo group, the authors wrote.
“Clinical and pharmacokinetic assessments from this trial are expected to continue for at least 12 months, with studies under way to evaluate the effectiveness of AZD7442 in immunocompromised persons who receive this agent as immunoprophylaxis under emergency use authorization,” Levin and colleagues wrote. “The results of this trial support the use of a single dose of AZD7442 (two consecutive intramuscular injections) for the prevention of symptomatic and severe COVID-19.”
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