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Dual Monoclonal Antibody Cuts COVID Risk in 8-Month Placebo Trial
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2022 CROI, February 12-16 and 22-24, 2022
Mark Mascolini
A single shot of two monoclonal antibodies, casirivimab and imdevimab (CAS/IMD) lowered risk of symptomatic SARS-CoV-2 infection in people exposed to the coronavirus and enrolled in a double-blind, placebo-controlled trial [1]. Researchers from Regeneron Pharmaceuticals, the developer of CAS/IMD, proposed that the antibodies offer "a pre-exposure prophylaxis strategy for individuals who are unlikely to respond or be protected by vaccination."
CAS and IMD are noncompeting neutralizing monoclonal antibodies that bind to different regions of the SARS-CoV-2 spike protein, the key SARS=CoV-2 uses to slip into target cells. Regeneron researchers already reported 28-day results of this phase 3, double-blind, placebo-controlled trial involving household contacts of people with COVID-19: At day 28 a single 1200-mg subcutaneous dose of CAS/IMD cut the risk of symptomatic COVID-19 by 81% and the risk of symptomatic or asymptomatic COVID-19 by 66% [3]. The study took place from July 2020 to October 2021, as COVID vaccines became widely available in the spring of 2021, the SARS-CoV-2 Delta variant became dominant in the summer of 2021, and the Omicron variant had yet to ignite its surge.
Trial participants had to be at least 12 years old, household contacts of someone diagnosed with SARS-CoV-2 infection, and themselves asymptomatic and RT-qPCR-negative for the coronavirus. Researchers randomized them to CAS/IMD or placebo within 96 hours of the index case testing positive.
The 841 people randomized to CAS/IMD and the 842 randomized to placebo were similar in age (averages 42.6 and 42.5), body mass index (28.5 and 28.6 kg/m2), and proportions of males (45.1% and 47.5%), whites (86.7% and 84.6%), Hispanics (40.1% and 44.1%), blacks (8.4% and 10.2%), and Asians (2.9% and 2.6%).
Throughout 8 months of follow-up, CAS/IMD cut the risk of symptomatic COVID 81.2% (odds ratio 0.17, 95% confidence interval [CI] 0.10 to 0.27, P < 0.0001), while trimming the risk of symptomatic or asymptomatic COVID 68.2% (odds ratio 0.27, 95% CI 0.20 to 0.37, P < 0.0001). Month-by-month analysis showed that relative risk reduction for symptomatic and all COVID was greatest with CAS/IMD through month 5 then waned in months 6 to 8, when similar small numbers in the CAS/IMD group and the placebo group became infected.
Adverse event rates were similar or lower with CAS/IMD versus placebo. Proportions in those two groups with 1 or more treatment-emergent adverse events (TEAE) were 28.1% and 35.9%, 1 or more non-COVID TEAE 23.8% and 22.8%, 1 or more serious TEAE 1.7% and 1.6%, and any TEAE resulting in death 0.2% and 0.1%. None of the 5 deaths were attributed to study drug or COVID. The researchers noted that the higher overall TEAE rate in the placebo group probably resulted from the higher number of placebo recipients who acquired COVID.
Regeneron is developing "highly similar next-generation monoclonal antibodies" that remain active against Omicron and other known SARS-CoV-2 variants. The investigators suggested monoclonal antibody combinations may prove effective as SARS-CoV-2 PrEP for people unlikely to respond to vaccination.
References
1. O'Brien MP, Herman G, Forleo Neto E, et al. Casirivimab and imdevimab combination provides long-term protection against COVID-19. 2022 CROI, February 12-16 and 22-24, 2022. Abstract 104.
2. Hansen J, Baum A, Pascal KE, et al. Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail. Science. 2020;369:1010-1014. doi: 10.1126/science.abd0827. https://www.science.org/doi/10.1126/science.abd0827
3. O'Brien MP, Forleo-Neto E, Musser BJ, et al. Subcutaneous REGEN-COV antibody combination to prevent Covid-19. N Engl J Med. 2021;385:1184-1195. doi: 10.1056/NEJMoa2109682. https://www.nejm.org/doi/10.1056/NEJMoa2109682
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