Invivyd has aligned with the FDA on the design of a phase 3 trial evaluating the safety and immunology of the company's monoclonal antibody, VYD2311, vs mRNA COVID vaccines and in co-administration.
Earlier this month, Invivyd announced that it has reached alignment with the FDA on the design of LIBERTY, a phase 3 clinical trial that will evaluate the comparative safety and immunologic profile of its investigational monoclonal antibody VYD2311 against commercially available mRNA COVID vaccines. The study will also explore the safety and immune response when VYD2311 is administered at the same time as an mRNA COVID vaccine.
LIBERTY is part of Invivyd’s broader REVOLUTION clinical program, which aims to better characterize monoclonal antibody–mediated prophylaxis for COVID-19 and its potential benefits for vulnerable populations. Unlike prior studies conducted during the height of the pandemic, the company says LIBERTY is designed to carefully and prospectively examine safety and immunology under controlled conditions.
“Invivyd is aligning with the FDA to explore the safety and immunology of our medicines carefully and prospectively under well-controlled conditions,” Marc Elia, Chairman of Invivyd’s Board of Directors, said in a statement. “This work, including our anticipated LIBERTY trial, stands in stark contrast to the rapid, short-term work to characterize mRNA COVID vaccine safety and efficacy, as was required at the height of the COVID pandemic.”
The FDA, providing joint feedback from its drug and biologics centers, requested specific monitoring of adverse events of special interest associated with mRNA COVID vaccines in the LIBERTY trial. The agency cited the known risk of myocarditis and pericarditis, particularly in young adults following mRNA COVID vaccination. Invivyd noted that no similar monitoring requests have been made for its other clinical trials that do not include an mRNA vaccine arm.
The LIBERTY Phase 3 trial will directly compare the safety and immunology of VYD2311 with mRNA COVID vaccines and assess co-administration.
FDA-requested monitoring for myocarditis and pericarditis reflects known mRNA vaccine risks, not safety signals seen with Invivyd’s monoclonal antibodies.
Results from LIBERTY and the ongoing DECLARATION trial are intended to inform future COVID prevention strategies, particularly for vulnerable populations.
The company emphasized that myocarditis and pericarditis have not been observed in any Invivyd clinical trials to date, nor in postmarketing adverse event reports for Pemivibart, its authorized monoclonal antibody product. The inclusion of targeted safety monitoring in LIBERTY, Invivyd said, reflects the presence of an mRNA vaccine comparator rather than a concern specific to VYD2311.
“We are grateful for the FDA’s clear and constructive feedback to our LIBERTY trial design, which we believe underscores the shared urgency to study the safety of potential COVID prevention options,” Rachael Gerlach, PhD, senior vice president of Regulatory Affairs, Invivyd said in a statement. “As part of our REVOLUTION clinical program, we believe we can provide Americans with useful, contemporary information about safety and side effects for potential COVID prevention options.”
The LIBERTY trial builds on DECLARATION, Invivyd’s ongoing Phase 3, randomized, triple-blind, placebo-controlled study of VYD2311 for the prevention of symptomatic COVID-19. DECLARATION is designed to support a biologics license application and includes adults and adolescents with and without risk factors for severe disease. Top-line data from that trial are expected in mid-2026.
