Safety, Tolerability, and Efficacy of Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies for the Treatment of Ambulatory Adult and Pediatric Patients With COVID-19
Summary
Phase 1 * To evaluate the safety and tolerability of REGN10933+REGN10987 compared to placebo * To evaluate the virologic efficacy of REGN10933+REGN10987 compared to placebo in reducing viral load of SARS-CoV-2 Phase 2 • To evaluate the virologic efficacy of REGN10933+REGN10987 compared to placebo in reducing viral load of SARS-CoV-2 Phase 3 * Cohort 1 (≥18 Years Old, Not Pregnant at Randomization) • To evaluate the clinical efficacy of REGN10933+REGN10987 compared to placebo as measured by COVID-19-related hospitalizations or all-cause death * Cohort 2 (\<18 Years Old, Not Pregnant at Randomization) * To evaluate the safety and tolerability of REGN10933+REGN10987 compared to placebo * To further characterize the concentrations of REGN10933 and REGN10987 in serum over time * Cohort 3 (Pregnant at Randomization) • To evaluate the safety and tolerability of REGN10933+REGN10987
Timeline
- Start
- 2020-06-16
- Primary completion
- 2022-01-21
- Completion
- 2022-06-09
Outcome
Met primary endpoint
Stopped: “Emerging SARS-CoV-2 variants impacting susceptibility to study drug”
paper Both REGEN-COV doses reduced viral load faster than placebo; PMID 34587383 ↗
registry analysis (superiority test); Phase 1 + Phase 2 Symptomatic (Placebo) vs Phase 1 + Phase 2 Symptomatic (2.4g IV); p = 0.0006; NCT04425629 ↗
registry analysis (superiority test); Phase 1 + Phase 2 Symptomatic (Placebo) vs Phase 1 + Phase 2 Symptomatic (8.0g IV); p < 0.0001; NCT04425629 ↗
registry analysis (superiority test); Phase 3 Cohort 1 (Placebo) >=18 vs Phase 3 Cohort 1 (1.2g IV) >= 18; p = 0.0024; NCT04425629 ↗
registry analysis (superiority test); Phase 3 Cohort 1 (Placebo) >=18 vs Phase 3 Cohort 1 (2.4g IV) >= 18; p < 0.0001; NCT04425629 ↗
release “clear clinical efficacy on reducing the rate of hospitalization and death with both the 1,200 mg and 2,400 mg doses of REGEN-COV compared to placebo” regeneron.com ↗
release “The phase III outcomes trial in high-risk non-hospitalised patients with COVID-19 met its primary endpoint” roche.com ↗
release “Phase 3 treatment trial in high-risk COVID-19 outpatients. The trial met its primary endpoint, showing that REGEN-COV significantly reduced the risk of hospitalization or death” regeneron.com ↗
release “The trial met its primary and all secondary endpoints and showed treatment with REGEN-COV significantly reduced the risk of hospitalization or death” regeneron.com ↗
release “REGN-COV 2067). The phase III outcomes trial in high-risk non-hospitalised patients with COVID-19 met its primary endpoint” roche.com ↗
release “In March 2021, the Company announced positive top-line results from the Phase 3 treatment trial in high-risk COVID-19 outpatients. The trial met its primary endpoint” regeneron.com ↗
Publications
- Norton TD, Thakur M, Ganguly S, Ali S, Chao J, Waldron A, Xiao J, Patel Y, Turner KC, Davis JD, Irvin SC, Pan C, Atmodjo-Watkins D, Hooper AT, Hamilton JD, Subramaniam D, Bocchini JA, Kowal B, DiCioccio AT, Bhore R, Geba GP, Cox E, Braunstein N, Dakin P, Herman GA. Assessing the safety and pharmacokinetics of casirivimab and imdevimab (CAS+IMD) in a cohort of pregnant outpatients with COVID-19: results from an adaptive, multicentre, randomised, double-blind, phase 1/2/3 study. BMJ Open. 2024 Oct 8;14(10):e087431. doi: 10.1136/bmjopen-2024-087431.
- Rofail D, Hussein M, Naumann U, Podolanczuk AJ, Norton T, Ali S, Mastey V, Ivanescu C, Hirshberg B, Geba GP. Patient-Reported Outcomes in COVID-19 Treatment with Monoclonal Antibodies Reveal Benefits in Return to Usual Activities. Infect Dis Ther. 2024 Aug;13(8):1861-1876. doi: 10.1007/s40121-024-01013-1. Epub 2024 Jul 3.
- Murayama A. Industry Payments to Pediatricians in the United States Between 2013 and 2021. Clin Pediatr (Phila). 2024 Oct;63(9):1308-1317. doi: 10.1177/00099228231218850. Epub 2023 Dec 15.
- Bermejo-Gomez A, Aguilera-Alonso D, Rincon-Lopez EM, Catalan-Alonso P, Bardon-Cancho EJ, Garcia-Morin M, Manrique-Rodriguez S, Navarro-Gomez ML. Use of Monoclonal Antibodies in a Pediatric Patient With Severe Combined Immunodeficiency and Persistent SARS-CoV-2 Infection. Pediatr Infect Dis J. 2023 Aug 1;42(8):e290-e292. doi: 10.1097/INF.0000000000003938. Epub 2023 Apr 27.
- Hirsch C, Park YS, Piechotta V, Chai KL, Estcourt LJ, Monsef I, Salomon S, Wood EM, So-Osman C, McQuilten Z, Spinner CD, Malin JJ, Stegemann M, Skoetz N, Kreuzberger N. SARS-CoV-2-neutralising monoclonal antibodies to prevent COVID-19. Cochrane Database Syst Rev. 2022 Jun 17;6(6):CD014945. doi: 10.1002/14651858.CD014945.pub2.
- Weinreich DM, Sivapalasingam S, Norton T, Ali S, Gao H, Bhore R, Xiao J, Hooper AT, Hamilton JD, Musser BJ, Rofail D, Hussein M, Im J, Atmodjo DY, Perry C, Pan C, Mahmood A, Hosain R, Davis JD, Turner KC, Baum A, Kyratsous CA, Kim Y, Cook A, Kampman W, Roque-Guerrero L, Acloque G, Aazami H, Cannon K, Simon-Campos JA, Bocchini JA, Kowal B, DiCioccio AT, Soo Y, Geba GP, Stahl N, Lipsich L, Braunstein N, Herman G, Yancopoulos GD; Trial Investigators. REGEN-COV Antibody Combination and Outcomes in Outpatients with Covid-19. N Engl J Med. 2021 Dec 2;385(23):e81. doi: 10.1056/NEJMoa2108163. Epub 2021 Sep 29.
- Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.
- Weinreich DM, Sivapalasingam S, Norton T, Ali S, Gao H, Bhore R, Musser BJ, Soo Y, Rofail D, Im J, Perry C, Pan C, Hosain R, Mahmood A, Davis JD, Turner KC, Hooper AT, Hamilton JD, Baum A, Kyratsous CA, Kim Y, Cook A, Kampman W, Kohli A, Sachdeva Y, Graber X, Kowal B, DiCioccio T, Stahl N, Lipsich L, Braunstein N, Herman G, Yancopoulos GD; Trial Investigators. REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19. N Engl J Med. 2021 Jan 21;384(3):238-251. doi: 10.1056/NEJMoa2035002. Epub 2020 Dec 17.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | casirivimab | Monoclonal antibody | — | Intravenous |
| Subject | imdevimab | Monoclonal antibody | — | Intravenous |