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Dual mAb Prevents Symptomatic COVID-19 in Household-Exposed Group: Interim Results of Placebo-Controlled Trial
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CROI 2021, Conference on Retroviruses and Opportunistic Infections, March 6-10, 2021
Mark Mascolini
Interim results of an ongoing placebo-controlled trial showed that a combination of two subcutaneously administered monoclonal antibodies (mAb), casirivimab and imdevimab, prevented symptomatic COVID-19 infection, halved the overall infection rate, and lowered viral load and viral shedding in people exposed to SARS-CoV-2 in household contacts [1]. Rates of grade 3 or serious treatment-emergent adverse events were low in both treated and placebo participants.
The FDA gave the double-mAb, REGEN-COV, emergency use authorization for treatment of mild to moderate COVID-19 in people 12 years old or older and weighing at least 40 kg (88 lb) who run a high risk of progression to severe disease or hospital admission [2]. The approved dose is 2400 mg (1200 mg of casirivimab and 1200 mg of imdevimab) infused over at least 60 minutes. Former President Trump got REGEN-COV for this COVID-19 infection [3].
REGEN-COV from Regeneron Pharmaceuticals combines two mAbs that bind to different regions of the SARS-CoV-2 spike protein, which the virus uses to enter cells. Prior research shows that REGEN-COV prevents quick emergence of escape mutations seen with single mAbs [4]. The double-mAb cocktail maintains activity against worrying SARS-CoV-2 mutants spreading from the UK, South Africa, and Brazil [5].
An ongoing phase 3 placebo-controlled trial includes adults and adolescents who are asymptomatic household contacts of a person diagnosed with SARS-CoV-2 infection [6]. Participants get tested for SARS-CoV-2 and assigned to cohort A if negative and to cohort B if positive. This analysis involved cohort A members who completed at least 29 days of the study after being assigned to placebo or REGEN-COV at a dose of 1200 mg (600 mg of each mAb) given within 96 hours of their household contact's positive SARS-CoV-2 test.
The analyzed REGEN-COV group included 186 people and the placebo group 223. The treatment and placebo groups had median ages of 43 (interquartile range [IQR] 28 to 56) and 45 (IQR 30 to 55), 57% and 52% were female, 52% and 46% Hispanic, 78.5% and 78% white, 11% and 14% black, and 3.2% and 2.7% Asian. Median body mass index stood at 29.4 kg/m2 (just below the obesity threshold) in both study arms.
No one in the REGEN-COV arm versus 8 of 223 (3.6%) in the placebo arm acquired symptomatic PCR-positive SARS-CoV-2 infection during follow-up. Proportions with any PCR-positive test, symptomatic or asymptomatic, were 10 of 186 (5.4%) with the mAbs versus 23 of 223 (10.3%) with placebo (odds ratio [OR] 0.49, 95% confidence interval [CI] 0.20 to 1.12, not significant).
No one receiving REGEN-COV versus 13 of 212 (6.1%) getting placebo became SARS-CoV-2-positive with a viral load above 10,000 copies/mL. While 8 of 179 people (4.5%) assigned to REGEN-COV tested positive with a viral load above 1000 copies/mL, 19 of 212 (9%) taking placebo had a viral load that high (OR 0.48, 95% CI 0.18 to 1.17, not significant). The placebo group had an average 100-fold higher peak viral load than the mAb group. Viral shedding lasted about 1 week in people assigned to REGEN-COV, while about 40% in the placebo group had 3 to 4 weeks of viral shedding.
To date, 54 of 267 people (20.2%) taking REGEN-COV had one or more treatment-emergent adverse events, compared with 77 of 286 people (26.9%) taking placebo. Three people (1.1%) assigned to REGEN-COV and 4 (1.4%) assigned to placebo had one or more serious treatment-emergent adverse events. No one taking REGEN-COV and 1 person taking placebo had a treatment-emergent adverse event resulting in withdrawal from the trial or death (cardiac arrest in a seropositive person apparently not related to SARS-CoV-2 infection).
The researchers concluded that this interim analysis of an ongoing phase 3 trial shows that REGEN-COV prevented symptomatic SARS-CoV-2 infection, lowered the overall infection rate, and decreased viral load and viral shedding in people exposed to a SARS-CoV-2-positive household contact. They added that people considered in this interim analysis will not be included in the final efficacy analysis of this trial.
References
1. O'Brien MP, Neto EF, Chen KC, et al. Casirivimab with imdevimab antibody cocktail for COVID-19 prevention: interim results. CROI 2021, Conference on Retroviruses and Opportunistic Infections, March 6-10, 2021. Abstract 123.
2. regeneroneua.com. REGEN-COV™ (casirivimab with imdevimab) Emergency Use Authorization (EUA) https://www.regeneroneua.com/
3. Arthur R. Regeneron's COVID-19 antibody cocktail receives EUA from FDA. BioPharma-Reporter.com. November 23, 2020. https://www.biopharma-reporter.com/Article/2020/11/23/Regeneron-s-COVID-19-antibody-cocktail-receives-EUA-from-FDA
4. Baum A, Fulton BO, Wloga E, et al. Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science. 2020;369:1014-1018. doi: 10.1126/science.abd0831. https://science.sciencemag.org/content/369/6506/1014.long
5. Wang P, Liu L, Iketani S, et al. Increased resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7 to antibody neutralization. bioRxiv. January 26, 2021. doi: https://doi.org/10.1101/2021.01.25.428137
6. ClinicalTrials.gov. COVID-19 study assessing the efficacy and safety of anti-spike SARS CoV-2 monoclonal antibodies for prevention of SARS CoV-2 infection asymptomatic in healthy adults and adolescents who are household contacts to an individual with a positive SARS CoV-2 RT-PCR assay. ClinicalTrials.gov identifier NCT04452318. https://clinicaltrials.gov/ct2/show/NCT04452318
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