Invivyd, Inc. has announced the upload of a manuscript preprint to MedRxiv detailing clinical efficacy data from the CANOPY phase 3 clinical trial of pemivibart, an investigational monoclonal antibody (mAb) for the pre-exposure prophylaxis (PrEP) of COVID-19. The data indicates long-term protection against recent JN.1 sublineages, even at low residual titers. The CANOPY trial's data supported the emergency use authorization (EUA) of Pemgarda (pemivibart) by the US FDA for PrEP of COVID-19 in certain moderate-to-severe immunocompromised patients.
CANOPY Trial Efficacy Data
The CANOPY clinical trial, conducted during a period of substantial COVID-19 transmission in the US, provided exploratory clinical efficacy data from Cohort B, a placebo-controlled cohort of immunocompetent individuals at risk of symptomatic COVID-19. These individuals were at risk due to regular unmasked face-to-face interactions in indoor settings. The safety profile of pemivibart remains consistent with the Pemgarda Fact Sheet for Healthcare Providers.
Long-Term Protection Against Emerging Variants
Previous disclosures from Invivyd highlighted the strong protection against symptomatic disease conferred by Pemgarda across multiple SARS-CoV-2 variants. Six-month data from a JN.1 dominant wave during active dosing showed an 84% relative risk reduction in symptomatic disease versus placebo. Long-term follow-up from months 7-12 after drug cessation demonstrated a 64% relative risk reduction in symptomatic disease versus placebo during a KP.3 and KP.3.1.1 wave.
The publication of the CANOPY clinical trial's long-term follow-up data is particularly significant, demonstrating that pemivibart provided strong protection over a 12-month period. This supports Invivyd's efforts to develop enhanced and more scalable product forms. Furthermore, the data indicates that strong protection was conferred during the off-drug interval in the trial, even with low, residual titer levels.
Novel Methodology for Predicting Antibody Activity
Invivyd scientists also uploaded a preprint to BioRxiv describing a novel methodology for assessing and predicting the structure-neutralization relationships between authorized or approved antibodies and novel viral variants. This approach aims to add speed and confidence to overall assessments of antibody activity. The preprint, authored by Powers, et al., details the use of a large panel of close molecular relatives to pemivibart to interrogate neutralization behavior across the panel against emerging variants of interest.
This molecular panel approach enhances the gold-standard pseudovirus assessment of authentic pemivibart at Labcorp-Monogram Biosciences by examining a large group of similarly structured variants of pemivibart with overlapping assessed binding sites. This creates a probabilistic cloud of likely pemivibart neutralization activity against variants of interest. This panel approach previously predicted ongoing neutralization activity for pemivibart against KP.3.1.1 and predicts continued neutralization activity against XEC, with formal assay assessment pending.
Expert Commentary
Dr. Robert Allen, Ph.D., chief scientific officer at Invivyd, commented on the importance of rigorous assessment of antibody activity. He stated, "Academic labs continue to make claims about 'pemivibart' activity that do not reflect the data outputs for Pemgarda (pemivibart) when Invivyd’s industrial-grade processes with authentic pemivibart are utilized...we have developed a systematic mechanism to parse the structural basis of individual neutralization results prospectively using a multi-antibody panel approach. Such an approach adds confidence and context to our understanding of the neutralization data we ultimately submit to FDA for their continued evaluation of the risk-benefit profile of Pemgarda."
