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

• Published in: International journal of infectious diseases Vol. 122; pp. 585 - 592
• Main Authors: Isa, Flonza, Forleo-Neto, Eduardo, Meyer, Jonathan, Zheng, Wenjun, Rasmussen, Scott, Armas, Danielle, Oshita, Masaru, Brinson, Cynthia, Folkerth, Steven, Faria, Lori, Heirman, Ingeborg, Sarkar, Neena, Musser, Bret J., Bansal, Shikha, O'Brien, Meagan P., Turner, Kenneth C., Ganguly, Samit, Mahmood, Adnan, Dupljak, Ajla, Hooper, Andrea T., Hamilton, Jennifer D., Kim, Yunji, Kowal, Bari, Soo, Yuhwen, Geba, Gregory P., Lipsich, Leah, Braunstein, Ned, Yancopoulos, George D., Weinreich, David M., Herman, Gary A.
• Format: Journal Article
• Language: English
• Published: Canada Elsevier Ltd 01.09.2022; The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases; Elsevier
• Subjects: Adult; Antibodies, Monoclonal, Humanized; Casirivimab; COVID-19; COVID-19 - prevention & control; COVID-19 Drug Treatment; Double-Blind Method; Humans; Imdevimab; Monoclonal antibody; SARS-CoV-2; COVID-19; SARS-CoV-2; Imdevimab; Monoclonal antibody; Casirivimab
• ISSN: 1201-9712; 1878-3511; 1878-3511
• DOI: 10.1016/j.ijid.2022.06.045

•Phase 1 study assessed monthly casirivimab+imdevimab (CAS+IMD) in uninfected adults•Repeat monthly CAS+IMD (1200 mg subcutaneously [SC]) was well-tolerated, with low immunogenicity•CAS+IMD (1200 mg SC) showed a substantial risk reduction in COVID-19 occurrence 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. [Display omitted]