Invivyd, Inc. announced positive 12-month exploratory clinical efficacy data from the CANOPY Phase 3 clinical trial of pemivibart (Pemgarda), an investigational monoclonal antibody (mAb) for the pre-exposure prophylaxis (PrEP) of COVID-19. The data, presented at the ACIP meeting, showed a 76% relative risk reduction (RRR) in symptomatic COVID-19 over a 12-month period (nominal p < 0.0001). This includes a period where participants were not actively dosed with the drug, demonstrating sustained protection.
The CANOPY trial included two cohorts: immunocompromised individuals (Cohort A) and immunocompetent adults at risk of exposure (Cohort B). The reported 76% RRR is based on data from Cohort B. The study evaluated the safety, tolerability, and efficacy of pemivibart as a preventive measure against COVID-19.
Sustained Protection During Off-Drug Follow-Up
Notably, during the six-month off-drug follow-up period (months 7-12), the pemivibart group exhibited a 64% reduction in the risk of symptomatic COVID-19 compared to the placebo group (p=0.0285). This protection occurred despite substantially reduced concentrations of Pemgarda, coinciding with the summer surge of KP.3 and KP.3.1.1 variants in the U.S., per CDC surveillance. In the placebo arm, participants experienced an 18% rate of PCR-confirmed symptomatic COVID-19, excluding reinfections, highlighting the continued widespread transmission of the virus.
Impact of Low Antibody Titers
Invivyd’s Chief Scientific Officer, Robert Allen, PhD, emphasized the significance of these results, noting that mAbs like pemivibart can confer protection even at low serum concentrations. The 64% RRR observed during months 7-12 occurred at calculated average serum virus neutralizing antibody (sVNA) titers of only approximately 7% of the average titers during the active dosing period. Allen stated, "Engineered mAbs are designed to confer a step change in protection compared to the protection possible from native immune response to infection and vaccination boosts."
Safety Profile
The safety profile of pemivibart over the 12-month study period was consistent with previous findings. No new treatment-emergent adverse events (TEAEs) were reported during the follow-up period. In Cohort A, the most common TEAEs (>5%) included upper respiratory tract infection (URTI) (10.1%), viral infection (8.8%), and urinary tract infection (UTI) (5.6%). Anaphylaxis was observed in 4 participants (0.6%) in Cohort A. In Cohort B, the most common TEAEs in the pemivibart arm included viral infection (8.5%), URTI (8.5%), and influenza-like illness (5.7%), with higher percentages in the placebo arm. No participants in Cohort B developed anaphylaxis.
Implications for Future mAb Development
These findings support the potential of engineered mAbs to enhance immunity compared to natural infection or vaccination alone. Invivyd is exploring multiple dosing routes, including intramuscular administration, to optimize protective strategies against COVID-19 and continues to develop mAb candidates that offer longer-lasting protection while aligning with regulatory guidelines. Their current pipeline molecule, VYD2311, is currently in Phase 1 testing, including intramuscular (IM) administration.
PEMGARDA EUA and Usage
PEMGARDA™ (pemivibart) is a half-life extended investigational monoclonal antibody (mAb) authorized for emergency use by the U.S. FDA for the pre-exposure prophylaxis (prevention) 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 due to certain medical conditions or receipt of certain immunosuppressive medications or treatments and are unlikely to mount an adequate immune response to COVID-19 vaccination.
