Invivyd Highlights Phase III Data Despite FDA Variant Concern

Invivyd recently unveiled promising results for its COVID-19 pre-exposure prophylaxis, reporting an impressive 84% relative risk reduction in healthy individuals. In a late-stage study, only six of several hundred participants contracted the virus. However, these positive findings were slightly overshadowed by an FDA announcement earlier in the week. The FDA cautioned that Pemgarda (pemivibart), Invivyd’s SARS-CoV-2 neutralizing monoclonal antibody (mAb), might offer reduced protection against the predominant SARS-CoV-2 variant currently circulating in the U.S.

Pemgarda had previously received emergency use authorization (EUA) from the FDA in March. This approval was based on data showing that individuals who received the prophylactic achieved serum neutralizing antibody titers against COVID-19 at levels consistent with those known to be protective. The latest update from Invivyd revealed 180-day data from the ongoing Phase III CANOPY trial. Besides the 316-person all-comer arm, the study included a cohort of 298 immunocompromised individuals. In the all-comer arm, the confirmed symptomatic COVID-19 rate was 1.9%, while the immunocompromised group had a rate of 3%. These rates compare favorably against the 11.9% rate observed in the 160-person placebo group.

Participants who received Pemgarda and subsequently contracted COVID-19 experienced only mild or moderate cases. Mark Wingertzahn, Invivyd’s senior vice president of clinical development and medical affairs, emphasized the significance of these results. He remarked that the study demonstrates that mAbs "can provide meaningful protection against COVID-19 when people encounter the virus in indoor settings and unmasked during their everyday lives." He also noted that the data suggest Pemgarda can offer additional protection even amid a substantial population-level backdrop of immunologic experience with SARS-CoV-2, whether from prior infection or vaccination.

The CANOPY trial data was collected during the September 2023 to March 2024 wave, dominated by the XBB and JN.1 variants. However, as of August 2024, the dominant COVID-19 variants in the U.S. have shifted to KP.3.1.1 and KP.3. The former accounts for approximately 37% of circulating variants, and the latter comprises 17%.

This significant shift in variant prevalence led the FDA to take precautionary measures. On Monday, the agency restricted Pemgarda’s EUA, limiting its use to situations where the combined national frequency of variants with substantially reduced susceptibility to Pemgarda is 90% or less. The FDA reported that Pemgarda likely has "adequate neutralization activity" against the KP.3 variant. However, early, non-peer-reviewed data suggest that KP.3.1.1 might exhibit "substantially reduced susceptibility" to the prophylactic.

These developments underscore the dynamic nature of the pandemic and the continuous need for vigilance and adaptability in public health responses. While Pemgarda demonstrates significant efficacy in certain conditions, the evolving landscape of COVID-19 variants necessitates ongoing monitoring and potential adjustments in treatment protocols. Invivyd's work contributes valuable insights into the fight against the virus, highlighting both the progress made and the challenges that remain in managing COVID-19 effectively.