Invivyd (NASDAQ:IVVD) reported topline results from its Phase III LIBERTY study of VYD2311, an investigational low-dose intramuscular monoclonal antibody designed to prevent COVID-19, and outlined plans to pursue an accelerated-approval pathway with the U.S. Food and Drug Administration.
The company said LIBERTY met its safety and tolerability objectives, showing a statistically significant advantage for VYD2311 compared with an mRNA COVID-19 vaccine over both six-day and 56-day follow-up periods. The active-controlled study enrolled 210 healthy adults and compared 250 mg of VYD2311, Pfizer-BioNTech’s COMIRNATY vaccine, and a combination of the two treatments.
Safety and tolerability findings
The safety and tolerability advantage over vaccination remained during the full 56-day assessment period, Mina said. There were no cases of hypersensitivity, anaphylaxis, myocarditis or pericarditis in any study arm.
LIBERTY did not include a placebo arm, meaning the study cannot establish how VYD2311’s adverse-event profile compares with ordinary background events in a placebo-controlled population. Invivyd said that comparison is expected from its ongoing DECLARATION study.
The company also reported that injection-site reactions were substantially less common with VYD2311 than with vaccination alone. Mina said the risk difference for injection-site reactions was greater than 60% in the vaccine-only arm compared with the monoclonal-antibody arm.
Combination with vaccination
Invivyd said the combination of VYD2311 and COVID-19 vaccination appeared to improve vaccine tolerability without reducing the immune response produced by the vaccine.
To assess whether VYD2311 interfered with vaccine-derived neutralizing antibodies, the company used an anti-idiotype antibody to remove VYD2311 from blood samples before measuring the remaining vaccine-induced response. Mina said the resulting immune-response curves were essentially identical between vaccine alone and the combination arm after VYD2311 was removed.
The company said total neutralizing titers were higher in the combination arm than with vaccine alone, reflecting the addition of the monoclonal antibody. However, Invivyd cautioned that existing assays do not provide established clinical correlates sufficient to estimate vaccine efficacy from those immunogenicity results.
Marc Elia, Invivyd’s chairman and chief executive officer, said the combination data may be relevant for people seeking additional protection against COVID-19. He also said the company sees VYD2311 as an attractive standalone option, citing market research in which approximately 85% of respondents chose the monoclonal antibody when presented with the company’s proposed product profiles for VYD2311 and COVID-19 vaccines.
Regulatory strategy and DECLARATION plans
Invivyd plans to seek accelerated approval for VYD2311 based on serum virus-neutralizing antibody titers, which the company argues are reasonably likely to predict clinical benefit. Elia said the company has generated placebo-controlled data with related antibodies in previous studies, including EVADE and CANOPY, and believes those data establish a quantitative relationship between neutralizing titers and COVID-19 prevention.
The company recently held a Type C meeting with the FDA regarding the potential accelerated-approval framework. Elia said Invivyd had not yet received the agency’s final meeting minutes but that the company’s submitted minutes did not identify an area of scientific disagreement with FDA.
Invivyd expects its placebo-controlled DECLARATION study to provide further safety and immunogenicity data for VYD2311. The company said results have been delayed by several weeks from prior guidance as it works through regulatory and federal-government discussions.
Elia said DECLARATION includes both a single-dose arm and a multiple-dose arm involving three doses administered one month apart. The company expects the initial filing regimen to be based on the core DECLARATION design.
Rather than waiting solely for clinical-event data before pursuing a filing, Invivyd intends to use safety and immunogenicity data from DECLARATION to support a biologics license application, if the results are supportive. It also plans to add another cohort of subjects to the same study infrastructure to gather additional clinical events and further support statistical power in a confirmatory setting.
The company said it is continuing commercial preparations for VYD2311, which it hopes could provide an option as the emergency use authorization for its current product, PEMGARDA, winds down next summer. PEMGARDA is authorized for prevention of COVID-19 in certain immunocompromised individuals but requires a one-hour intravenous infusion, post-infusion monitoring and quarterly dosing.
About Invivyd (NASDAQ:IVVD)
Invivyd, Inc is a clinical-stage biopharmaceutical company focused on developing antibody-based medicines designed to prevent and treat viral diseases. The company’s approach is intended to provide durable protection against rapidly evolving viruses by using engineered monoclonal antibodies that can be updated as pathogens change.
Invivyd’s leading product is pemivibart, marketed in the United States under the brand name PEMGARDA. The product received emergency use authorization from the U.S.
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