Emergency Use Authorization Sought for Novel Monoclonal Antibody for COVID-19 in Immunocompromised Individuals

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Invivyd, Inc. has filed a request with the FDA for emergency use authorization (EUA) for VYD222, a broadly neutralizing, half-life extended monoclonal antibody developed specifically to prevent COVID-19 in immunocompromised adults and adolescents. The EUA submission was based on positive initial findings from the pivotal Phase III CANOPY clinical trial for VYD222 and data for ongoing in vitro neutralization activity against relevant COVID-19 variants. VYD222 was found to demonstrate a potent response against multiple SARS-CoV-2 variants currently circulating, including the fastest growing variant in the United States, JN.1, as well as HV.1, BA.2.86, XBB.1.5.10/EG.5, and HK.3.

"We are tremendously pleased by the fact that VYD222 continues to demonstrate in vitro neutralization activity against the latest dominant variant, JN1, as well as other prevalent SARS-CoV-2 strains,” said Dave Hering, Invivyd chief executive officer, in a press release. “We believe that the demonstrated durability of VYD222 is reflective of our strategy to select antibody candidates that target conserved epitopes to achieve our stated goal of keeping pace with viral evolution.”

The CANOPY trial enrolled approximately 750 individuals in two cohorts across multiple trial sites in the United States. Cohort A included approximately 300 significantly immunocompromised individuals to receive a 4500 mg intravenous (IV) infusion of VYD222. The primary endpoints for Cohort A were safety and tolerability, and serum neutralizing titers against relevant SARS-CoV-2 variants at day 28, which were analyzed based on the pharmacokinetic concentration of VYD222 from immunocompromised individuals and the IC50 value for VYD222 against relevant SARS-CoV-2 variants.

Cohort B enrolled approximately 450 individuals at risk of exposure to SARS-CoV-2, who were randomly assigned 2:1 to receive either 4500 mg VYD222 or placebo administered via IV infusion. The primary endpoints for this cohort included safety and tolerability, and the proportion of patients with RT-PCR-confirmed symptomatic COVID-19 through six months.

The trial’s primary efficacy analysis involved an immunobridging approach that evaluated data collected in the CANOPY clinical trial compared to specific historical data from a prior Phase II/III clinical trial of adintrevimab (ADG20) for the prevention of symptomatic COVID-19 (EVADE). This trial found that serum neutralizing titers correlated with observed clinical efficacy.

Data from CANOPY found that VYD222 produced high serum virus neutralizing antibody (sVNA) titer levels against the XBB15 variant among immunocompromised individuals. The trial also found a promising potential early signal of clinical protection from symptomatic COVID-19 based on the high sVNA titer levels and dose selected, according to the investigators.

"We are eagerly tracking the progress of new monoclonal antibodies because there are still countless immunocompromised people who remain vulnerable to the ravages of COVID-19,” Seth Ginsberg, president and co-founder, Global Healthy Living Foundation, said in a press release. “Sustained innovation is what is needed to keep pace with this virus, and we commend Invivyd and others working in this space for their commitment and dedication to serving those who are in urgent need of protection."

Investigators noted that the initial findings from the CANOPY trial support an immunobridging approach with in vitro VYD222 potency data used to calculate and efficiently determine sVNA titer levels against new, emerging SARS-CoV-2 variants. Initial data showed that the safety and tolerability profile of VYD222 was favorable with no reported serious adverse events related to VYD222.

“The submission of the EUA request for VYD222 represents an exciting milestone for Invivyd that was only made possible thanks to the unwavering dedication of our employees, the support of our investigators, and the invaluable contributions of all those who participated in the CANOPY trial,” Hering said in the release. “Many immunocompromised people do not achieve full benefit from COVID-19 vaccines as their immune systems are unable to provide sufficient defense against SARS-CoV-2. If authorized, we believe VYD222 could provide these vulnerable individuals with an important new preventive option.”

References

Invivyd Submits Request For Emergency Use Authorization (EUA) To U.S. FDA For VYD222 for the Pre-Exposure Prevention of Covid-19 in Immunocompromised Adults and Adolescents. Invivyd, Inc. News release. January 3, 2024. Accessed January 3, 2024. https://investors.invivyd.com/news-releases/news-release-details/invivyd-submits-request-emergency-use-authorization-eua-us-fda