Invivyd announced the publication of results from its landmark CANOPY Phase 3 clinical trial of PEMGARDA (pemivibart) in Clinical Infectious Diseases, demonstrating strong efficacy of the monoclonal antibody in preventing COVID-19 in a contemporary U.S. population facing immune-evasive SARS-CoV-2 variants. The trial achieved an 84% relative risk reduction in symptomatic COVID-19 compared to placebo during the six-month treatment period, with nominal statistical significance (p <0.0001).
Trial Design and Population
The CANOPY Phase 3 trial randomized 788 adult participants across 18 sites in two distinct cohorts from September 2023 to September 2024. Cohort A included immunocompromised individuals in a single-arm, open-label design, while Cohort B enrolled immunocompetent adults at risk of COVID-19 exposure through regular, unmasked face-to-face interactions in indoor settings in a randomized, placebo-controlled design.
The study represents a unique achievement in COVID-19 research as the first and only clinical trial of an authorized or approved COVID-19 monoclonal antibody or vaccine with placebo-controlled clinical efficacy data in a contemporary, seropositive U.S. population. Participants were already immunologically experienced at baseline from prior COVID-19 infection or vaccination and faced contemporary Omicron-lineage viruses.
Safety Profile
PEMGARDA demonstrated an acceptable safety profile throughout the 12-month trial period. The most common study drug-related adverse events were infusion-related reactions, occurring in 11 of 306 participants (3.6%) in Cohort A and 7 of 317 participants (2.2%) receiving pemivibart in Cohort B, compared to 0 of 160 participants receiving placebo. Of 623 participants who received pemivibart, 4 (0.6%) experienced anaphylactic reactions, with 2 classified as serious.
The incidence of infusion-related reactions and hypersensitivity reactions in CANOPY was consistent with the range (<0.1%-13%) observed in non-immunocompromised participants who received intravenous monoclonal antibodies in previous COVID-19 clinical trials.
Regulatory and Clinical Context
The antiviral activity measured by calculated serum virus neutralizing antibody (sVNA) titers in CANOPY Cohort A supported the FDA's emergency use authorization (EUA) of PEMGARDA for pre-exposure prophylaxis of COVID-19 in certain moderate-to-severe immunocompromised patients. The exploratory efficacy results from Cohort B provide additional clinical evidence supporting PEMGARDA's effectiveness for COVID-19 prevention.
"Most people, including clinicians and policy makers, are not aware that COVID-19 killed more Americans last year than breast cancer or car accidents," said Cameron R. Wolfe, MD, MPH, Professor of Medicine, Transplant Infectious Disease at Duke University. "There is still an unacceptable burden of severe sickness and hospitalization, not to mention Long COVID, all of which is borne disproportionately by immunocompromised persons."
Mechanism and Viral Activity
PEMGARDA targets the SARS-CoV-2 spike protein receptor binding domain (RBD), inhibiting virus attachment to the human ACE2 receptor on host cells. The monoclonal antibody has demonstrated in vitro neutralizing activity against major SARS-CoV-2 variants, including JN.1, KP.3.1.1, XEC and LP.8.1. Pemivibart's ongoing antiviral activity against evolving SARS-CoV-2 variants remains within the range of expected assay variability, affirming its unique binding to a highly conserved, stable epitope.
Future Development
Marc Elia, Invivyd's Chairman of the Board, noted that the CANOPY trial data substantiate the use of sVNA titers as a valid surrogate endpoint for COVID-19 prevention to expedite approval of novel Invivyd antibodies such as VYD2311. The company expects to elaborate this possibility and the underlying data from CANOPY in a future publication.
VYD2311, Invivyd's next-generation monoclonal antibody candidate, was engineered using the company's proprietary integrated technology platform and may offer the ability to deliver clinically meaningful titer levels through more patient-friendly administration routes such as intramuscular injection.
PEMGARDA is currently authorized under EUA for pre-exposure prophylaxis of COVID-19 in adults and adolescents (12 years of age and older weighing at least 40 kg) who have moderate-to-severe immune compromise and are unlikely to mount an adequate immune response to COVID-19 vaccination.
