Invivyd reports positive Phase 3 LIBERTY results for VYD2311, showing favorable safety and tolerability versus an mRNA COVID-19 vaccine.
Written By: Saniya Katakdhond, PharmD
Reviewed By: Pharmacally Editorial Team
Invivyd announced topline results from LIBERTY, a Phase 3 randomized, double-blind, active-controlled study evaluating the safety, tolerability, pharmacokinetics, and neutralizing antibody responses of VYD2311.
The study enrolled 210 healthy adults aged 18–49 years. Participants were randomized in a 1:1:1 ratio to receive a single intramuscular dose of 250 mg VYD2311, an mRNA-based COVID-19 vaccine, or VYD2311 administered in combination with the mRNA-based vaccine.
The 250 mg VYD2311 dose evaluated in LIBERTY is also being studied in the ongoing Phase 3 DECLARATION trial. LIBERTY was designed as a companion study to DECLARATION, which is evaluating VYD2311 for pre-exposure prophylaxis of symptomatic COVID-19.
VYD2311 Demonstrated Favorable Short-Term Safety and Tolerability
The first co-primary endpoint assessed the proportion of participants experiencing any treatment-emergent adverse event (TEAE), injection-site reaction (ISR), or hypersensitivity reaction during the first six days after dosing.
These events occurred in 56.5% of participants receiving VYD2311 compared with 91.4% of participants receiving the mRNA-based COVID-19 vaccine (P<0.0001).
The second co-primary endpoint evaluated solicited systemic adverse events recorded through an electronic diary during the first six days. Systemic adverse events were reported in 44.1% of participants receiving VYD2311 compared with 68.1% receiving the mRNA-based vaccine (P=0.008).
In the combination group, 78.9% of participants experienced a TEAE, ISR, or hypersensitivity reaction compared with 91.4% in the vaccine-only group (P=0.057). Systemic adverse events occurred in 50.0% of participants receiving the combination compared with 68.1% receiving the mRNA-based vaccine alone (P=0.023).
Safety Findings Extended Through 56 Days
The key secondary endpoint assessed TEAEs, ISRs, or hypersensitivity reactions through 56 days following administration.
The event rate was 60.9% with VYD2311 compared with 91.4% with the mRNA-based vaccine (P<0.0001).
For the combination of VYD2311 and the mRNA-based vaccine, the corresponding rate was 83.1%, compared with 91.4% with the vaccine alone (P=0.21).
According to Invivyd, no adverse events related to VYD2311 were greater than Grade 2. No hypersensitivity or anaphylaxis events were observed in any treatment arm of the LIBERTY study.
VYD2311 Did Not Interfere with Vaccine-Induced Neutralizing Responses
LIBERTY also evaluated whether administration of VYD2311 alongside an mRNA-based COVID-19 vaccine affected vaccine-induced neutralizing antibody responses.
Invivyd reported no evidence of immunologic interference between VYD2311 and the mRNA-based vaccine. When administered together, the combination produced approximately a 2.5-fold increase in neutralizing titers compared with the mRNA-based vaccine alone over the 56-day study period.
To further evaluate the vaccine contribution within the combination, Invivyd analyzed samples after removing VYD2311. Neutralizing titers from these VYD2311-depleted samples were reported to be essentially comparable with those observed in the mRNA vaccine-only group.
These findings support the company’s assessment that VYD2311 did not interfere with the vaccine-induced neutralizing response in the LIBERTY study.
LIBERTY Data Inform the VYD2311 Development Program
VYD2311 pharmacokinetic findings from LIBERTY were reported to be consistent with Invivyd’s expectations, although definitive assessment remains pending in the ongoing DECLARATION study. Together with the candidate’s in vitro potency data against circulating SARS-CoV-2 variants, the company stated that these findings support its target neutralizing-antiviral-titer profile being evaluated in DECLARATION.
The combination findings also provide a basis for further investigation of VYD2311 administered alongside COVID-19 vaccination, although additional clinical studies would be required to evaluate this approach.
Invivyd Plans Potential BLA Submission
Invivyd said it has continued discussions with the U.S. Food and Drug Administration regarding the regulatory pathway for VYD2311, including a recent Type C meeting in September 2026.
Following these discussions, the company plans to pursue a Biologics License Application (BLA) under the FDA’s Accelerated Approval pathway, subject to supportive data from the ongoing DECLARATION study.
Invivyd plans to report placebo-controlled safety and neutralizing-antiviral-titer data from DECLARATION while keeping clinical efficacy events collected to date blinded. The company expects topline safety and immunogenicity data from DECLARATION in October 2026.
If the data support the planned regulatory strategy, Invivyd intends to pursue Accelerated Approval based on data from DECLARATION and LIBERTY, together with previously generated data from its monoclonal antibody programs.
If Accelerated Approval is granted, Invivyd plans to continue accumulating PCR-positive symptomatic COVID-19 events in a post-approval confirmatory randomized cohort to further evaluate clinical efficacy.
Clinical efficacy data from DECLARATION are planned to be unblinded after potential Accelerated Approval, subject to accumulation of the required clinical events.
VYD2311 and the DECLARATION Study
VYD2311 is an investigational monoclonal antibody being developed by Invivyd for COVID-19. The candidate was engineered using the company’s proprietary technology platform and is designed to neutralize contemporary SARS-CoV-2 lineages.
The ongoing DECLARATION study is a Phase 3 randomized, triple-blind, placebo-controlled trial evaluating VYD2311 for the prevention of symptomatic COVID-19. The study plans to enroll approximately 2,400 participants, including adults and adolescents with and without risk factors for progression to severe COVID-19.
Participants are being evaluated following either a single dose or monthly doses of VYD2311 administered by intramuscular injection.
The LIBERTY findings provide Phase 3 evidence on the safety, tolerability, pharmacokinetics, and neutralizing-antibody profile of VYD2311, while the upcoming DECLARATION data are expected to provide additional placebo-controlled evidence that will inform the candidate’s clinical and regulatory development.
Reference
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, Invivyd Inc. 29 September 2026
Safety and Serum Virus Neutralizing Antibody Responses of VYD2311, a COVID-19 Vaccine, and Coadministered VYD2311 With a COVID-19 Vaccine (LIBERTY), ClinicalTrials.gov ID NCT07655180
Study of VYD2311 for the Prevention of COVID-19 (DECLARATION), ClinicalTrials.gov ID NCT07298434
About the Writer
Saniya Sanjay Katakdhond (Linkedin) is a Doctor of Pharmacy professional with hands-on experience in patient case review, clinical documentation, medical record analysis, and patient care.
Her hospital experience has strengthened her understanding of clinical conditions, treatment approaches, and multidisciplinary healthcare practices.
With ICH-GCP certification and a research-oriented approach, she brings clinical insight and attention to detail to healthcare content development.
As a healthcare writer, Saniya focuses on translating clinical knowledge and patient-care experience into clear, accurate, and evidence-informed medical content.