Repeat subcutaneous administration of casirivimab and imdevimab in adults is well-tolerated and prevents the occurrence of COVID-19.

A phase 1, double-blind, placebo-controlled trial was conducted to evaluate the safety, tolerability, and exploratory efficacy of repeat monthly doses of subcutaneous (SC) casirivimab and imdevimab (CAS+IMD) in uninfected adult volunteers. Participants were randomized (3:1) to SC CAS+IMD 1200 mg or placebo every 4 weeks for up to six doses. Primary and secondary end points evaluated safety, pharmacokinetics, and immunogenicity. Exploratory efficacy was evaluated by the incidence of COVID-19 or SARS-CoV-2 seroconversion. In total, 969 participants received CAS+IMD. Repeat monthly dosing of SC CAS+IMD led to a 92.4% relative risk reduction in clinically defined COVID-19 compared with 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 occurred in a small proportion of participants (<5%). No grade ≥3 injection-site reactions (ISRs) or hypersensitivity reactions were reported. Slightly more participants reported treatment-emergent adverse events with CAS+IMD (54.9%) than with placebo (48.3%), a finding that was due to grade 1-2 ISRs. Serious adverse events were rare. No deaths were reported in the 6-month treatment period. Repeat monthly administration of 1200 mg SC CAS+IMD was well-tolerated, demonstrated low immunogenicity, and showed a substantial risk reduction in COVID-19 occurrence.

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Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declarations of competing interest FI, MPO, KCT, SG, JDH, and GAH are Regeneron employees/stockholders and have a patent pending, which has been licensed and receiving royalties, with Regeneron. EF-N, JM, WZ, LF, NS, BJM, SB, AM, AD, YK, BK, YS, GPG, LL, NB, and DMW are Regeneron employees/stockholders. CB reports grants or contracts from Gilead, Lilly, and GlaxoSmithKline for clinical trials. IH is a Regeneron consultant and Merck & Co. stockholder. ATH is a Regeneron employee/stockholder and former Pfizer employee and current stockholder. GDY is a Regeneron employee/stockholder and has issued patents (US Patent Nos. 10,787,501, 10,954,289, and 10,975,139) and pending patents, which have been licensed and receiving royalties, with Regeneron. SR, DA, MO, and SF have no conflicts to declare.