Efficacy and safety of a single dose of casirivimab and imdevimab for the prevention of COVID-19 over an 8-month period: a randomised, double-blind, placebo-controlled trial. Issue 10 (October 2022)

• Record Type: Journal Article
• Authors: Herman, Gary A; O'Brien, Meagan P; Forleo-Neto, Eduardo; Sarkar, Neena; Isa, Flonza; Hou, Peijie; Chan, Kuo-Chen; Bar, Katharine J; Barnabas, Ruanne V; Barouch, Dan H; Cohen, Myron S; Hurt, Christopher B; Burwen, Dale R; Marovich, Mary A; Musser, Bret J; Davis, John D; Turner, Kenneth C; Mahmood, Adnan; Hooper, Andrea T; Hamilton, Jennifer D; Parrino, Janie; Subramaniam, Danise; Baum, Alina; Kyratsous, Christos A; DiCioccio, A Thomas; Stahl, Neil; Braunstein, Ned; Yancopoulos, George D; Weinreich, David M; Chani, Achint; Adepoju, Adebiyi; Mahmood, Adnan; Mortagy, Aisha; Dupljak, Ajla; Baum, Alina; Brown, Alison; Froment, Amy; Hooper, Andrea; Margiotta, Andrea; Bombardier, Andrew; Islam, Anita; Smith, Anne; Dhillon, Arvinder; McMillian, Audra; Breazna, Aurora; Aslam, Ayesha; Carpentino, Barabara; Kowal, Bari; Siliverstein, Barry; Horel, Benjamin; Zhu, Bo; Musser, Bret; Bush, Brian; Head, Brian; Snow, Brian; Zhu, Bryan; Debray, Camille; Phillips, Careta; Simiele, Carmella; Lee, Carol; Nienstedt, Carolyn; Trbovic, Caryn; Chan, Casey (Kuo-Chen); Elliott, Catherine; Fish, Chad; Ni, Charlie; Polidori, Christa; Enciso, Christine; Caira, Christopher; Powell, Christopher; Kyratsous, Christos A.; Baum, Cliff; McDonald, Colin; Leigh, Cynthia; Pan, Cynthia; Wolken, Dana; Manganello, Danielle; Liu, David; Stein, David; Weinreich, David M.; Hassan, Dawlat; Gulabani, Daya; Fix, Deborah; Leonard, Deborah; Sarda, Deepshree; Bonhomme, Denise; Kennedy, Denise; Darcy, Devin; Barron, Dhanalakshmi; Hughes, Diana; Rofail, Diana; Kaur, Dipinder; Ramesh, Divya; Bianco, Dona; Cohen, Donna; Forleo-Neto, Eduardo; Jean-Baptiste, Edward; Bukhari, Ehsan; Doyle, Eileen; Bucknam, Elizabeth; Labriola-Tomkins, Emily; Nanna, Emily; Huffman O'Keefe, Esther; Gasparino, Evelyn; Fung, Evonne; Isa, Flonza; To, Fung-Yee; Herman, Gary; Yancopoulos, George D.; Bellingham, Georgia; Sumner, Giane; Moggan, Grainne; Power, Grainne; Zeng, Haixia; Mariveles, Hazel; Gonzalez, Heath; Kang, Helen; Noor, Hibo; Minns, Ian; Heirman, Ingeborg; Peszek, Izabella; Donohue, James; Rusconi, Jamie; Austin, Janice; Parrino, Janie; Yo, Jeannie; McDonnell, Jenna; Hamilton, Jennifer D.; Boarder, Jessica; Wei, Jianguo; Yu, Jingchun; Malia, Joanne; Tucciarone, Joanne; Tyler-Gale, Jodie; Davis, John D.; Strein, John; Cohen, Jonathan; Meyer, Jonathan; Ursino, Jordan; Im, Joseph; Tramaglini, Joseph; Wolken, Joseph; Potter, Kaitlyn; Scacalossi, Kaitlyn; Naidu, Kamala; Browning, Karen; Rutkowski, Karen; Yau, Karen; Woloshin, Katherine; Lewis-Amezcua, Kelly; Turner, Kenneth; Dornheim, Kimberly; Chiu, Kit; Mohan, Kosalai; McGuire, Kristina; Macci, Kristy; Ringleben, Kurt; Mohammadi, Kusha; Foster, Kyle; Knighton, Latora; Lipsich, Leah; Darling, Lindsay; Boersma, Lisa; Cowen, Lisa; Hersh, Lisa; Jackson, Lisa; Purcell, Lisa; Sherpinsky, Lisa; Lai, Livia; Faria, Lori; Geissler, Lori; Boppert, Louise; Fiske, Lyra; Dickens, Marc; Mancini, Marco; Leigh, Maria C.; O'Brien, Meagan P.; Batchelder, Michael; Klinger, Michael; Partridge, Michael; Tarabocchia, Michel; Wong, Michelle; Rodriguez, Mivianisse; Albizem, Moetaz; O'Byrne, Muriel; Braunstein, Ned; Sarkar, Neena; Stahl, Neil; Deitz, Nicole; Memblatt, Nicole; Shah, Nirav; Kumar, Nitin; Herrera, Olga; Adedoyin, Oluchi; Yellin, Ori; Snodgrass, Pamela; Floody, Patrick; D'Ambrosio, Paul; Gao, Paul (Xiaobang); Hou, Peijie; Hearld, Philippa; Li, Qin; Kitchenoff, Rachel; Ali, Rakiyya; Iyer, Ramya; Chava, Ravikanth; Alaj, Rinol; Pedraza, Rita; Hamlin, Robert; Hosain, Romana; Gorawala, Ruchin; White, Ryan; Yu, Ryan; Fogarty, Rylee; Dass, S. Balachandra; Bollini, Sagarika; Ganguly, Samit; DeCicco, Sandra; Patel, Sanket; Cassimaty, Sarah; Somersan-Karakaya, Selin; McCarthy, Shane; Henkel, Sharon; Ali, Shazia; Geila Shapiro, Shelley; Kim, Somang; Nossoughi, Soraya; Bisulco, Stephanie; Elkin, Steven; Long, Steven; Sivapalasingam, Sumathi; Irvin, Susan; Wilt, Susan; Min, Tami; Constant, Tatiana; Devins, Theresa; DiCioccio, Thomas; Norton, Thomas; Bernardo, Travis; Chuang, Tzu-Chien; Wei, Victor (Jianguo); Nuce, Vinh; Battini, Vishnu; Caldwell, Wilson; Gao, Xiaobang; Chen, Xin; Tian, Yanmei; Khan, Yasmin; Zhao, Yuming; Kim, Yunji; Dye, Bonnie; Hurt, Christopher B.; Burwen, Dale R.; Barouch, Dan H.; Burns, David; Brown, Elizabeth; Bar, Katharine J.; Marovich, Mary; Clement, Meredith; Cohen, Myron S.; Sista, Nirupama; Barnabas, Ruanne V.; Zwerski, Sheryl;
• Is Part Of: Lancet infectious diseases. Volume 22:Issue 10(2022)
• Page Start: 1444
• Page End: 1454
• Publication Date: 2022-10
• Subjects: Communicable diseases -- Periodicals; Infection -- Periodicals; Communicable Diseases -- Periodicals; Infection -- Periodicals; Maladies infectieuses -- Périodiques; Infection -- Périodiques; Communicable diseases; Infection; Periodicals; 616.905
• DOI: 10.1016/S1473-3099(22)00416-9
• Languages: English
• ISSNs: 1473-3099

Abstract

Summary: Background: There is an unmet need for COVID-19 prevention in patient populations who have not mounted or are not expected to mount an adequate immune response to complete COVID-19 vaccination. We previously reported that a single subcutaneous 1200 mg dose of the monoclonal antibody combination casirivimab and imdevimab (CAS + IMD) prevented symptomatic SARS-CoV-2 infections by 81·4% in generally healthy household contacts of SARS-CoV-2-infected individuals over a 1-month efficacy assessment period. Here we present additional results, including the 7-month follow-up period (months 2–8), providing additional insights about the potential for efficacy in pre-exposure prophylaxis settings. Methods: This was a randomised, double-blind, placebo-controlled trial done in the USA, Romania, and Moldova in 2020–2021, before the emergence of omicron (B.1.1.529) and omicron-lineage variants. Uninfected and unvaccinated household contacts of infected individuals, judged by the investigator to be in good health, were randomly assigned (1:1) to receive 1200 mg CAS + IMD or placebo by subcutaneous injection according to a central randomisation scheme provided by an interactive web response system; randomisation was stratified per site by the test results of a local diagnostic assay for SARS-CoV-2 and age group at baseline. COVID-19 vaccines were prohibited before randomisation, but participants were allowed to receive COVID-19 vaccination during the follow-up period. Participants who developed COVID-19 symptoms during the follow-up period underwent RT-PCR testing. Prespecified endpoints included the proportion of previously uninfected and baseline-seronegative participants (seronegative-modified full analysis set) who had RT-PCR-confirmed COVID-19 in the follow-up period (post-hoc for the timepoints of months 2–5 and 6–8 only) and underwent seroconversion (ie, became seropositive, considered a proxy for any SARS-CoV-2 infections [symptomatic and asymptomatic]; prespecified up to day 57, post-hoc for all timepoints thereafter). We also assessed the incidence of treatment-emergent adverse events. This study is registered with ClinicalTrials.gov, NCT04452318 . Findings: From July 13, 2020, to Oct 4, 2021, 2317 participants who were RT-PCR-negative for SARS-CoV-2 were randomly assigned, of whom 1683 (841 assigned to CAS + IMD and 842 assigned to placebo) were seronegative at baseline. During the entirety of the 8-month study, CAS + IMD reduced the risk of COVID-19 by 81·2% (nominal p<0·0001) versus placebo (prespecified analysis). During the 7-month follow-up period, protection was greatest during months 2–5, with a 100% relative risk reduction in COVID-19 (nominal p<0·0001; post-hoc analysis). Efficacy waned during months 6–8 (post-hoc analysis). Seroconversion occurred in 38 (4·5%) of 841 participants in the CAS + IMD group and in 181 (21·5%) of 842 in the placebo group during the 8-month study (79·0% relative risk reduction vs placebo; nominal p<0·0001). Six participants in the placebo group were hospitalised due to COVID-19 versus none who received CAS + IMD. Serious treatment-emergent adverse events (including COVID-19) were reported in 24 (1·7%) of 1439 participants receiving CAS + IMD and in 23 (1·6%) of 1428 receiving placebo. Five deaths were reported, none of which were due to COVID-19 or related to the study drugs. Interpretation: CAS + IMD is not authorised in any US region as of Jan 24, 2022, because data show that CAS + IMD is not active against omicron-lineage variants. In this study, done before the emergence of omicron-lineage variants, a single subcutaneous 1200 mg dose of CAS + IMD protected against COVID-19 for up to 5 months of community exposure to susceptible strains of SARS-CoV-2 in the pre-exposure prophylaxis setting, in addition to the post-exposure prophylaxis setting that was previously shown. Funding: Regeneron Pharmaceuticals, F Hoffmann-La Roche, US National Institute of Allergy and Infectious Diseases, US National Institutes of Health.