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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DOI record:
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"abstract": "<jats:title>Abstract</jats:title>\n <jats:sec>\n <jats:title>Background</jats:title>\n <jats:p>We report an interim analysis of safety and efficacy of pemivibart in individuals with (cohort A) or without (cohort B) significant immunocompromise in the phase 3 CANOPY trial.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Methods</jats:title>\n <jats:p>Eligible participants (≥18 years; negative for current SARS-CoV-2 infection) received 2 intravenous 4500-mg pemivibart infusions (cohort A) or were randomized 2:1 to receive blinded pemivibart or placebo (cohort B) 90 days apart. Safety was a primary endpoint for both cohorts. The primary immunobridging endpoint for cohort A has previously been reported. Composite incidence of reverse transcription-polymerase chain reaction-confirmed symptomatic COVID-19, COVID-19 hospitalization, and all-cause mortality was an exploratory endpoint.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Results</jats:title>\n <jats:p>In September-November 2023, 306 participants received pemivibart (cohort A); 317 received pemivibart and 162 placebo (cohort B). The most common study drug-related adverse events were 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 serious). In cohort A, the composite COVID-19 incidence through month 6 was 11/298 (3.7%; 2 deaths). In cohort B, 6/317 (1.9%; no deaths) and 19/160 (11.9%; no deaths) pemivibart and placebo participants, respectively, met the endpoint through month 6 (84.1% standardized relative risk reduction [RRR; 95% CI, 60.9-93.5; nominal P&lt;.0001]), and 15/317 (4.7%; 1 death) and 29/160 (18.1%; no deaths) pemivibart and placebo participants, respectively, met the endpoint through month 12 (73.9% standardized RRR [95% CI, 52.8-85.6; nominal P&lt;.0001]). Twelve month protection was conferred with no additional dosing.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Conclusions</jats:title>\n <jats:p>Pemivibart provided prophylactic efficacy against COVID-19 and was well-tolerated by most participants. Anaphylaxis was an important safety risk.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Clinical Trials Registration</jats:title>\n <jats:p>NCT06039449</jats:p>\n </jats:sec>",
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