Repeat Subcutaneous Administration of REGEN-COV® in Adults is Well-Tolerated and Prevents the Occurrence of COVID-19
MD Flonza Isa, Eduardo Forleo-Neto, Jonathan Meyer, Wenjun Zheng, Scott Rasmussen, Danielle Armas, Masaru Oshita, Cynthia Brinson, Steven Folkerth, Lori Faria, Ingeborg Heirman, Neena Sarkar, Bret J Musser, Shikha Bansal, Meagan P O’brien, Kenneth C Turner, Samit Ganguly, Adnan Mahmood, Ajla Dupljak, Andrea T Hooper, Jennifer D Hamilton, Yunji Kim, Bari Kowal, Yuhwen Soo, Gregory P Geba, Leah Lipsich, Ned Braunstein, George D Yancopoulos, David M Weinreich, Gary A Herman
doi:10.1101/2021.11.10.21265889
Background: Data show that a single dose of casirivimab and imdevimab (REGEN-COV ® ) is effective in treating hospitalized individuals and outpatients with COVID-19 and in post-exposure prophylaxis. We present results from a phase 1, double-blind, placebo-controlled trial evaluating the safety, tolerability, and efficacy of repeat monthly doses of subcutaneous (SC) REGEN-COV in uninfected adult volunteers who were healthy or had chronic stable medical conditions. Methods: Subjects were randomized (3:1) to SC REGEN-COV 1200 mg or placebo dosed every 4 weeks for up to 6 doses. The primary and secondary endpoints evaluated the safety, pharmacokinetics, and immunogenicity of multiple-dose administration of REGEN-COV. Efficacy was evaluated by the incidence of COVID-19 or SARS-CoV-2 seroconversion.
Results: In total, 969 subjects were treated. Repeat monthly dosing of SC REGEN-COV led to a 92.4% relative risk reduction in clinically-defined COVID-19 compared to placebo (3/729 [0.4%] vs 13/240 [5.4%]; odds ratio: 0.07 [95% CI, 0.01-0.27]), and a 100% reduction in laboratory-confirmed COVID-19 (0/729 vs 10/240 [4.2%]; odds ratio 0.00). Development of anti-drug antibodies was low (<5% subjects). No grade ≥3 injection-site reactions (ISRs) or hypersensitivity reactions were reported. A slightly higher percentage of subjects reported TEAEs with REGEN-COV (54.9%) than placebo (48.3%), due to ISRs (all grade 1-2). Serious adverse events were rare and occurred at similar percentages in the REGEN-COV and placebo groups. No deaths were reported in the 6-month treatment period.
Notes
References
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DOI record:
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"abstract": "<jats:p><jats:bold>Background:</jats:bold> Data show that a single dose of casirivimab and imdevimab (REGEN-COV®) is effective in treating hospitalized individuals and outpatients with COVID-19 and in post-exposure prophylaxis. We present results from a phase 1, double-blind, placebo-controlled trial evaluating the safety, tolerability, and efficacy of repeat monthly doses of subcutaneous (SC) REGEN-COV in uninfected adult volunteers who were healthy or had chronic stable medical conditions.\n\n<jats:bold>Methods:</jats:bold> Subjects were randomized (3:1) to SC REGEN-COV 1200 mg or placebo dosed every 4 weeks for up to 6 doses. The primary and secondary endpoints evaluated the safety, pharmacokinetics, and immunogenicity of multiple-dose administration of REGEN-COV. Efficacy was evaluated by the incidence of COVID-19 or SARS-CoV-2 seroconversion.\n\n<jats:bold>Results:</jats:bold> In total, 969 subjects were treated. Repeat monthly dosing of SC REGEN-COV led to a 92.4% relative risk reduction in clinically-defined COVID-19 compared to placebo (3/729 [0.4%] vs 13/240 [5.4%]; odds ratio: 0.07 [95% CI, 0.01–0.27]), and a 100% reduction in laboratory-confirmed COVID-19 (0/729 vs 10/240 [4.2%]; odds ratio 0.00). Development of anti-drug antibodies was low (<5% subjects). No grade ≥3 injection-site reactions (ISRs) or hypersensitivity reactions were reported. A slightly higher percentage of subjects reported TEAEs with REGEN-COV (54.9%) than placebo (48.3%), due to ISRs (all grade 1-2). Serious adverse events were rare and occurred at similar percentages in the REGEN-COV and placebo groups. No deaths were reported in the 6-month treatment period. \n\n<jats:bold>Conclusions:</jats:bold> Repeated monthly administration of 1200 mg SC REGEN-COV was well-tolerated with low immunogenicity, and showed a substantial risk reduction in COVID-19 occurrence.\n\n(ClinicalTrials.gov identifier, <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT04519437\">NCT04519437</jats:ext-link>)</jats:p>",
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