NEW HAVEN, Conn. — September 29, 202

Invivyd announced topline results from the Phase 3 LIBERTY study evaluating VYD2311, an investigational monoclonal antibody for COVID-19, compared with an mRNA-based COVID-19 vaccine and the combination of both approaches. The randomized, double-blind, active-controlled study enrolled 210 healthy adults aged 18 to 49 years and met its primary and key secondary safety and tolerability endpoints. VYD2311 produced lower rates of treatment-emergent adverse events, injection-site reactions or hypersensitivity reactions and solicited systemic adverse events compared with the mRNA vaccine. Over six days, 56.5% of participants receiving VYD2311 experienced a treatment-emergent adverse event, injection-site reaction or hypersensitivity reaction versus 91.4% with the mRNA vaccine (P<0.0001), while systemic adverse events occurred in 44.1% versus 68.1%, respectively (P=0.008). Invivyd plans to use LIBERTY and upcoming DECLARATION data to support a potential U.S. Biologics License Application.

LIBERTY Demonstrates VYD2311 Safety and Tolerability Profile

The LIBERTY study evaluated VYD2311 at a 250 mg intramuscular dose, the same dose being studied in the ongoing DECLARATION pivotal trial. The co-primary endpoints assessed overall safety and tolerability during the first six days and solicited systemic adverse events over the same period. The key secondary endpoint assessed treatment-emergent adverse events, injection-site reactions or hypersensitivity reactions through Day 56. VYD2311 showed a 56.5% incidence for the six-day overall safety endpoint compared with 91.4% for the mRNA vaccine, while the 56-day incidence was 60.9% versus 91.4%, respectively, with both comparisons reaching statistical significance at P<0.0001. Systemic adverse events occurred in 44.1% of VYD2311 recipients versus 68.1% of mRNA vaccine recipients during the first six days. Invivyd reported that no VYD2311-related adverse events exceeded Grade 2 and that no hypersensitivity or anaphylaxis was observed in any study arm.

Combination With mRNA Vaccine Adds Neutralizing Activity

LIBERTY also evaluated whether administering VYD2311 together with an mRNA-based COVID-19 vaccine would interfere with vaccine-induced immune responses. Invivyd reported that the combination did not materially reduce vaccine-induced neutralizing titers and instead increased neutralizing titers by approximately 2.5-fold over the 56-day study compared with the mRNA vaccine alone. Analysis of combination samples after depletion of VYD2311 produced neutralizing titers essentially comparable to those observed with the vaccine-only arm, which the company said supports a lack of immunologic interference. Pharmacokinetic findings from LIBERTY were also reported to be consistent with Invivyd’s expectations, although definitive assessment of the VYD2311 profile remains dependent on data from the ongoing DECLARATION study. The combination findings represent an additional area for potential future investigation rather than an established clinical benefit.

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Invivyd Plans BLA Submission Following DECLARATION Data

Invivyd plans to use the LIBERTY results together with safety and immunogenicity data from the ongoing Phase 3 DECLARATION study as the basis for a potential BLA submission under the FDA Accelerated Approval pathway. Following a recent Type C meeting with the FDA, the company expects to report DECLARATION safety and neutralizing antiviral titer data in October while keeping accumulated clinical efficacy events blinded. If the data support submission and accelerated approval is granted, Invivyd plans to continue collecting blinded PCR-positive symptomatic COVID-19 events through a post-approval confirmatory randomized cohort. DECLARATION is evaluating VYD2311 in approximately 2,400 participants, including adults and adolescents with and without risk factors for severe COVID-19, using single-dose and monthly-dose regimens. VYD2311 remains investigational, and the regulatory pathway, approval decision and clinical efficacy profile remain subject to FDA review and additional clinical data.

Source :Invivyd press release