Safety and Efficacy of Pemivibart, a Long-Acting Monoclonal Antibody, for Prevention of Symptomatic COVID-19: Interim Results From the CANOPY Clinical Trial
Cameron R Wolfe, Jonathan Cohen, Kathryn Mahoney, Anna Holmes, Natalia Betancourt, Deepali Gupta, Kazima Tosh, Kristin Narayan, Ed Campanaro, Chloe Katz, Anne-Marie Phelan, Ilker Yalcin, Mark Wingertzahn, Pamela Hawn, Pete Schmidt, Yong Li, Myra Popejoy
doi:10.1101/2024.11.11.24317127
Key points: Pre-exposure prophylactic administration of 2 doses of pemivibart approximately 90 days apart was generally well-tolerated and provided protection against symptomatic COVID-19 through 6 months in individuals with immunocompromise and 12 months in individuals without immunocompromise, respectively.
Author contributions M.P., A.H., Y.L., I.Y., E.C., and K.N. contributed to study design. M.P., A.H., Y.L., I.Y., D.G., K.N., E.C., and A.P. were involved in protocol development. J.C. was a principal investigator. M.P., A.H., K.M., and N.B. were responsible for medical monitoring. All authors contributed to data interpretation and were involved in drafting and critically revising the manuscript, and all authors approved the final version and are accountable for the accuracy and integrity of the manuscript. All authors had full access to the data in the study and had final responsibility for the decision to submit for publication. Y. L., D.G., and K.N. verified the data.
Potential conflicts of interest. Investigative sites and institutions were compensated by Invivyd, Inc. for all participant visits, including enrollment/baseline and follow-up. K.M., A.H., N.B., D.G., K.T., K.N., E.C., C.K., A.P., I.Y., M.W., P.H., P.S., Y.L., and M.P. were employees of Invivyd, Inc., at the time the study was conducted and may hold stock or shares in Invivyd, Inc.
Data availability As this trial is ongoing, data are not publicly available. Participants may have >1 immunocompromising condition or medication or risk factor for COVID-19 progression. c Taking high-dose corticosteroids (≥20 mg of prednisone or equivalent per day for at least 2 weeks), B-cell-depleting agents (within the past year), alkylating agents, antimetabolites, transplant-related immunosuppressive drugs, TNF blockers,..
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'abstract': '<jats:p>Background: Pemivibart received emergency-use authorization for prevention of '
'symptomatic COVID-19 in moderate-to-severe immunocompromised individuals based on '
'immunobridging analysis in the phase 3 CANOPY trial. We report an interim analysis of safety '
'and efficacy of pemivibart in individuals with (cohort A) or without (cohort B) significant '
'immunocompromise over a contemporary variant landscape. Methods: Eligible participants (aged '
'≥18 years; SARS-CoV-2-negative) received 2 intravenous 4500-mg pemivibart infusions (cohort '
'A) or received blinded pemivibart or placebo (2:1, cohort B) 90 days apart. Safety was a '
'primary endpoint. Composite incidence of reverse transcription-polymerase chain reaction '
'(RT-PCR)-confirmed symptomatic COVID-19, COVID-19 hospitalization, or all-cause mortality was '
'evaluated through month 6 (cohort A) and month 12 (cohort B). Results: In September-November '
'2023, 306 participants with immunocompromise received pemivibart in cohort A; 317 received '
'pemivibart and 162 received placebo in cohort B. The most common study drug-related adverse '
'event was infusion-related reactions (cohort A: 11/306 [3.6%]; cohort B: 7/317 [2.2%, '
'pemivibart] and 0/162 [placebo]). Four of 623 (0.6%) participants who received pemivibart '
'experienced anaphylactic reactions (2 non-serious; 2 serious) within 24 hours of dosing. In '
'cohort A, the composite COVID-19 endpoint incidence through month 6 (day 180) was 11/298 '
'(3.7%; 2 deaths [suicide and unknown cause]) in participants who received a first full dose '
'of pemivibart. In cohort B, the composite COVID-19 endpoint incidence through month 6 was '
'6/317 (1.9%) in participants in the pemivibart group and 19/160 (11.9%) in the placebo group, '
'representing an 84.1% standardized relative risk reduction (RRR) (95% CI, 60.9-93.5; nominal '
'P<.0001) for pemivibart. Through month 12, 15/317 (4.7%; 1 death [cardiac failure]) and '
'29/160 (18.1%) pemivibart and placebo participants met the composite clinical endpoint, '
'respectively demonstrating a 73.9% standardized RRR (95% CI, 52.8-85.6; nominal P<.0001). '
'Conclusions: Pemivibart provided pre-exposure prophylactic efficacy against COVID-19 and was '
'well-tolerated by most participants with or without significant immunocompromise. Anaphylaxis '
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