The investigational monoclonal antibody, VYD2311, (Invivyd) met all primary and key secondary endpoints in the phase 3 LIBERTY study. It showed safety and tolerability superior to an mRNA-based COVID-19 vaccine.¹ Invivyd also reported VYD2311 did not interfere with vaccine-induced neutralizing titers when coadministered.¹
LIBERTY is a companion study to DECLARATION, the ongoing placebo-controlled pivotal trial of VYD2311 for pre-exposure prophylaxis of symptomatic COVID-19.¹ Invivyd plans to use data from both studies to support a Biologics License Application (BLA) under the FDA Accelerated Approval Program, following a Type C meeting in September.¹
Phase 3 Results
LIBERTY, a randomized, double-blind, active-controlled phase 3 trial, enrolled 210 healthy adults aged 18 to 49 years.¹ Participants were randomly assigned 1:1:1 to a single 250-mg intramuscular dose of VYD2311, Comirnaty (COVID-19 vaccine, mRNA; Pfizer-BioNTech), or both agents combined. Every participant received 2 injections, with volume-matched placebo used to preserve blinding.¹
Over the first 6 days after dosing, 56.5% of VYD2311 recipients had a treatment-emergent adverse event (TEAE), injection site reaction or hypersensitivity reaction, compared with 91.4% of vaccine recipients (P < .0001).¹ Solicited systemic adverse events (AEs) occurred in 44.1% of the VYD2311 arm and 68.1% of the vaccine arm over the same period (P = .008).¹
For the key secondary endpoint across the full 56-day study, 60.9% of VYD2311 recipients had a TEAE, injection site reaction or hypersensitivity reaction, compared with 91.4% of vaccine recipients (P < .0001).¹ The combination arm had significantly fewer systemic AEs than vaccine alone at 6 days (50.0% vs 68.1%; P = .023). Its overall safety rates were numerically lower at 6 days (78.9% vs 91.4%; P = .057) and 56 days (83.1% vs 91.4%; P = .21).¹ No VYD2311-related AEs exceeded grade 2, and no hypersensitivity or anaphylaxis occurred in any arm.¹
What You Need to Know
Over 6 days, 56.5% of VYD2311 recipients had a treatment-emergent adverse event, injection site reaction or hypersensitivity reaction, compared with 91.4% of mRNA vaccine recipients (P < .0001).
Giving VYD2311 with the mRNA vaccine raised neutralizing titers about 2.5-fold over vaccine alone, with no sign of immunologic interference.
Invivyd plans to seek FDA Accelerated Approval for VYD2311 based on the LIBERTY and DECLARATION data, and DECLARATION topline safety and immunogenicity results are expected in October.
How VYD2311 May Complement COVID-19 Vaccination
Invivyd engineered VYD2311 on its proprietary technology platform, using serial molecular evolution to optimize neutralization of contemporary SARS-CoV-2 lineages.¹ It shares an antibody backbone with pemivibart, which has emergency use authorization for pre-exposure prophylaxis of symptomatic COVID-19 in certain immunocompromised patients, and with adintrevimab.¹ According to the company, the pharmacokinetic profile and potency of VYD2311 may deliver clinically meaningful titers through intramuscular administration.¹
In LIBERTY, adding VYD2311 to the mRNA vaccine raised neutralizing titers about 2.5-fold over vaccine alone across 56 days.¹ When investigators removed VYD2311 from combination samples, the remaining titers were essentially identical to those in the vaccine-only arm, confirming no immunologic interference.¹ Observed pharmacokinetics matched company expectations, although definitive demonstration awaits DECLARATION.¹
"The LIBERTY data provide us with high confidence in the profile of VYD2311. With placebo-controlled safety and neutralizing antiviral titer data for VYD2311 still pending from the DECLARATION study, this formal comparison of VYD2311 to standard of care COVID-19 mRNA vaccine provides an important window into VYD2311's clinical profile," said Michael Mina, MD, PhD, chief medical officer and chief epidemiologist of Invivyd, in a statement.¹
DECLARATION topline safety and immunogenicity data are expected in October. Clinical efficacy data will stay blinded and are planned for release after approval, if granted, subject to event accrual.¹ The company's efficacy target is a 70% to 90% relative risk reduction in PCR-confirmed symptomatic COVID-19 vs placebo.¹
About VYD2311
VYD2311 is a novel monoclonal antibody candidate being developed for COVID-19 to continue to address the urgent need for new prophylactic and therapeutic options. The pharmacokinetic profile and antiviral potency of VYD2311 may offer the ability to deliver clinically meaningful titer levels through more patient-friendly means such as an intramuscular route of administration.
VYD2311 was engineered using Invivyd’s proprietary integrated technology platform and is the product of serial molecular evolution designed to generate an antibody optimized for neutralizing contemporary virus lineages. VYD2311 leverages the same antibody backbone as pemivibart, Invivyd’s investigational mAb granted emergency use authorization in the US for the pre-exposure prophylaxis (PrEP) of symptomatic COVID-19 in certain immunocompromised patients, and adintrevimab, Invivyd’s investigational mAb that has a robust safety data package and demonstrated clinically meaningful results in global Phase 2/3 clinical trials for the prevention and treatment of COVID-19.
References
1.Invivyd announces positive topline results from LIBERTY phase 3 study demonstrating VYD2311 safety and tolerability superior to mRNA-based COVID-19 vaccine; announces regulatory submission plans for VYD2311. News release. Invivyd, Inc. September 29, 2026. Accessed September 29, 2026. https://investors.invivyd.com/news-releases/news-release-details/invivyd-announces-positive-topline-results-liberty-phase-3-study
