By Stan Deresinski, MD, FACP, FIDSA
Synopsis: Confirming the results of the immunobridging analysis that led to its initial authorization for emergency use, this study demonstrates that pemivibart is effective as prophylaxis against COVID-19, including in immunocompromised patients.
Source: Wolfe CR, Cohen J, Mahoney K, et al. Safety and efficacy of pemivibart, a long-acting monoclonal antibody, for prevention of symptomatic COVID-19: Interim results from a phase 3 randomized clinical trial (CANOPY). Clin Infect Dis. 2025;May 24:ciaf265. doi: 10.1093/cid/ciaf265. [Online ahead of print].
Wolfe and colleagues report the safety and clinical outcome results of the CANOPY trial evaluating the safety and efficacy of pemivibart, a human monoclonal antibody with a prolonged half-life, in the prophylaxis of COVID-19. The study was performed at 18 U.S. sites that enrolled adult subjects in two cohorts with initial dosing in September 2023 and data cutoff in May 2024.
The clinical efficacy was defined by a composite endpoint of reverse transcription polymerase chain reaction (RT-PCR)-confirmed symptomatic COVID-19 with onset of symptoms 14 days or less from positive sample collection, COVID-19-related hospitalization, and all-cause mortality through month 3 following a single dose of pemivibart, as well as at six months and 12 months (cohort B only) following two doses of pemivibart given 90 days apart.
Cohort A was an open-label study in which 306 subjects with significant immunocompromise each received two individual 4,500 mg intravenous (IV) infusions of pemivibart 90 days apart. In this cohort, the composite endpoint occurred in 3/298 subjects (1.0%; no deaths) through month 3 and in 11/298 subjects (3.7%; two deaths) through month 6. No COVID-19-related hospitalizations occurred through month 6. The time-to-event analysis showed that the estimated probability of the composite endpoint was 0.8% (95% confidence interval [CI], 0.2-2.7) through day 90 and 4.1% (95% CI, 2.1-7.1) through month 6.
Cohort B was a randomized (2:1), triple-blind, placebo-controlled study that enrolled 484 adults at risk of acquiring SARS-CoV-2 infection but without significant immunocompromise to receive either pemivibart (N = 317) or placebo (N = 162); 296 and 154 participants, respectively, received a second dose at 90 days. The month 3 composite endpoint occurred in 1/317 (0.3%) pemivibart recipients and 8/160 (5.0%) placebo recipients, with all the endpoints in each group due to symptomatic SARS-CoV-2 infection. Thus, pemivibart administration was associated with a 93.7% (95% CI, 50.3-99.2; nominal P = 0.0087) relative risk reduction (RRR) at three months. Assessment at six months found that six (1.9%) pemivibart recipients and 19 (11.9%) placebo recipients, respectively, met the composite endpoint for an RRR of 84.1% (95% CI, 60.9-93.5; nominal P < 0.0001). At 12 months, the composite endpoint occurred in 15 (4.7%) pemivibart recipients and 29 (18.1%) placebo recipients, for a 73.9% RRR (95% CI, 52.8-85.6; nominal P < 0.0001). It can be calculated from the absolute risk difference of 13.4% that the number needed to treat to prevent one COVID-19 infection over the 12-month follow-up period was seven.
Overall, pemivibart was well tolerated, with the major risk observed being the occurrence of anaphylaxis, which occurred in 4/623 (0.6%) pemivibart recipients — all in Cohort A. Only two of these reactions, each of which occurred during redosing, were considered serious, while two non-serious infusion-related hypersensitivity reactions treated with oral diphenhydramine occurred after the initial dose.
Commentary
Remember any of these: bamlanivimab, tixagevimab-cilgavimab, casirivimab-imdevimab? These were monoclonal antibodies that received U.S. Food and Drug Administration (FDA) Emergency Use Authorization (EUA) for use in COVID-19 prophylaxis in selected at-risk populations. However, as SARS-CoV-2 evolved, these agents lost their ability to inhibit the virus, especially the Omicron sublineages, and by the end of 2022, all were deauthorized. This left many patients, including those with significant immunocompromse, at risk. In September 2024, though, another prophylactic monoclonal, pemivibart, received EUA status for use in uninfected individuals not recently known to be exposed to COVID-19 who had moderate-to-severe immunocompromise and were judged to be unlikely to mount an adequate response to vaccination.
Pemivibart targets epitopes on the viral spike glycoprotein, impairing binding of SARS-CoV-2 to its receptor. It has a prolonged half-life (approximately 49 days) due to an altered Fc receptor. The EUA for pemivibart was based on immunobridging analysis of data from the CANOPY trial in which it was determined that the serum level of SARS-CoV-2 neutralizing antibody achieved at time points after administration were consistent with those achieved with other monoclonals that had been demonstrated to prevent COVID-19. Pemivibart appeared relatively safe, but there was, at the time, no clinical evidence demonstrating protective efficacy.
The CANOPY study was performed in the face of the inevitably evolving COVID-19 landscape. Enrollment spanned the prevalence of two major viral variants — JN.1 and KP.3.11, which emerged during the study, but the most recent Centers for Disease Control and Prevention data (May 11-24, 2025) indicate that these accounted for 0% and 1% of variants, respectively. At the same time, more than 98% of study patients had been vaccinated and/or experienced COVID-19. Nonetheless, this study demonstrates the significant efficacy of pemivibart in prevention of COVID-19, although there was no placebo arm in Cohort A for ethical reasons since this cohort enrolled patients with immunocompromise. Overall, these included 66% who were taking immunosuppressive medications, 13% with hematologic malignancies, 12% with primary immunodeficiencies, and 11% who were recipients of solid organ transplants. These are the patients most likely to benefit from effective prophylaxis.
Stan Deresinski, MD, FACP, FIDSA, is Clinical Professor of Medicine, Stanford University.
Confirming the results of the immunobridging analysis that led to its initial authorization for emergency use, this study demonstrates that pemivibart is effective as prophylaxis against COVID-19, including in immunocompromised patients.
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