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Randomized Controlled Trial
. 2022 Sep:122:585-592.
doi: 10.1016/j.ijid.2022.06.045. Epub 2022 Jul 2.

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

Flonza Isa  1 , Eduardo Forleo-Neto  2 , Jonathan Meyer  3 , Wenjun Zheng  3 , Scott Rasmussen  4 , Danielle Armas  5 , Masaru Oshita  6 , Cynthia Brinson  7 , Steven Folkerth  8 , Lori Faria  3 , Ingeborg Heirman  3 , Neena Sarkar  3 , Bret J Musser  3 , Shikha Bansal  3 , Meagan P O'Brien  3 , Kenneth C Turner  3 , Samit Ganguly  3 , Adnan Mahmood  3 , Ajla Dupljak  3 , Andrea T Hooper  3 , Jennifer D Hamilton  3 , Yunji Kim  3 , Bari Kowal  3 , Yuhwen Soo  3 , Gregory P Geba  3 , Leah Lipsich  3 , Ned Braunstein  3 , George D Yancopoulos  3 , David M Weinreich  3 , Gary A Herman  3 ; for the COVID-19 Multi-dose Trial Team
Affiliations
Randomized Controlled Trial

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

Flonza Isa et al. Int J Infect Dis. 2022 Sep.

Abstract

Objectives: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: COVID-19; Casirivimab; Imdevimab; Monoclonal antibody; SARS-CoV-2.

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Conflict of interest statement

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.

Figures

Image, graphical abstract
Graphical abstract
Figure 1
Figure 1
Cumulative incidence of symptomatic SARS-CoV-2 infection during the treatment period. COVID-19, coronavirus disease 2019; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2. The proportion of participants with the reported adverse event of SARS-CoV-2 infection compared with the number of participants at risk for infection in the CAS+IMD group and placebo group is shown by study day. Symptomatic SARS-CoV-2 (COVID-19) determination was made by the investigator on the basis of clinical assessment.
Figure 2
Figure 2
Concentrations of casirivimab, imdevimab, and casirivimab+imdevimab in serum over time. D, day; LLOQ, lower limit of quantification; SC, subcutaneous. Serum concentration of casirivimab, imdevimab, and casirivimab+imdevimab (CAS+IMD) in serum are depicted by study day. Sample collection visits on day 91 and day 208 were included in the original version of the protocol but were removed in protocol amendment 3.
See this image and copyright information in PMC

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