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News|Articles|October 1, 2026
VYD2311 Shows Superior Safety vs mRNA COVID-19 Vaccine
Author(s)Sabrina McCrear
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Key Takeaways
- LIBERTY met all primary/secondary endpoints, with lower 6-day TEAEs/ISRs/hypersensitivity (56.5% vs 91.4%) and systemic AEs (44.1% vs 68.1%) for VYD2311 than vaccine.
- Over 56 days, TEAEs/ISRs/hypersensitivity remained lower with VYD2311 (60.9% vs 91.4%), and no VYD2311-related events exceeded grade 2 or included anaphylaxis.
Invivyd's VYD2311 shows superior safety and tolerability vs Comirnaty in the phase 3 LIBERTY trial, with no vaccine interference.
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Invivyd’s investigational next-generation monoclonal antibody (mAb), VYD2311, demonstrated clinically and statistically superior safety and tolerability when compared with the mRNA-based
VYD2311’s safety and tolerability, both in comparison and combination with a current COVID-19 vaccine, were evaluated in LIBERTY (
This investigational antibody, which Invivyd describes as a vaccine alternative, is positioned as a pre-exposure prophylaxis therapy for COVID-19. This makes it Invivyd’s second drug currently targeting pre-exposure prophylaxis for COVID-19. Although neither is FDA-approved, and one, pemivibart (Pemgarda; Invivyd), is under emergency use authorization (EUA) for certain immunocompromised individuals,2,3 nonvaccine prophylaxis options could play a growing role in the prevention landscape, as COVID-19
“The observed profile of VYD2311 in LIBERTY and measured in vitro potency data of VYD2311 against circulating variants leave us confident and looking forward to the placebo-controlled safety and immunogenicity data we expect shortly in the DECLARATION study,” Marc Elia, chairman and CEO of Invivyd, said in a press release. “We want to move as quickly as possible to the regulatory filings required to bring Americans a new choice in protection from COVID.”
LIBERTY Trial Design and End Points
The coprimary end points evaluated the proportion of participants experiencing treatment-emergent adverse events (TEAEs), injection site reactions (ISRs), or hypersensitivity reactions and those experiencing systemic adverse events (AEs) within the first 6 days following dosing.1 The key secondary end point evaluated all of the coprimary endpoints, except for systemic AEs, but over the full 56 days following dosing.
Within 6 days of dosing, 56.5% of participants receiving VYD2311 experienced a TEAE, ISR, or hypersensitivity reaction vs 91.4% of those receiving the vaccine (P < .0001), and 44.1% vs 68.1% experienced systemic AEs (P = .008). Over 56 days, the rates of TEAEs, ISRs, or hypersensitivity reactions were 60.9% vs 91.4% (P < .0001). No AEs related to VYD2311 were higher than grade 2, and no hypersensitivity or anaphylaxis was observed in any arm.1
Participants in the study were randomized to receive either 250 mg of VYD2311 intramuscularly, the mRNA-based COVID-19 vaccine, or both VYD2311 and Comirnaty. When administered in conjunction with the mRNA-based COVID-19 vaccine, VYD2311 increased overall neutralizing titers about 2.5 times compared with the vaccine alone over the 56-day study.1
How VYD2311 Compares With Pemivibart
What makes this potential PrEP option interesting is that it’s developed with the same antibody backbone as Invivyd’s
Their structures also differ as VYD2311 was engineered through serial molecular evolution to optimize neutralization of contemporary virus lineages.2 Pemivibart is only authorized under EUA for patients who are immunocompromised and less likely to respond to a COVID-19 vaccine, and its EUA states that it is not a substitute for vaccination in individuals for whom COVID-19 vaccination is recommended.3
In contrast, Invivyd is studying VYD2311 in a broader population. The 210 participants in LIBERTY were healthy adults aged 18 to 49 years, and the DECLARATION trial includes adults and adolescents with and without risk factors for severe COVID-19.1
According to Invivyd, the LIBERTY trial data suggest that when VYD2311 is administered concomitantly with the mRNA-based COVID-19 vaccine, it may improve the vaccine’s safety and tolerability while adding to neutralizing antibody titers.1 In the combination arm, systemic AEs were significantly lower than with the vaccine alone (50.0% vs 68.1%; P = .023), and differences in overall TEAEs, ISRs, or hypersensitivity reactions did not reach statistical significance at 6 days (P = .057) or 56 days (P = .21).1
“LIBERTY has generated the first phase 3, randomized, blinded, controlled data we are aware of in history that compare different mechanisms for achieving immunization in vulnerable humans,” Elia said in the press release.
For payers and providers grappling with the financial and health outcomes associated with COVID-19, a potential alternative to vaccines could represent a significant paradigm shift in the future.
For younger adults aged 18 to 49 years, vaccination required greater investment and was cost-effective only under specific conditions. A second dose was not economically favorable for non-immunocompromised adults younger than 65 years.5
Although cost data for VYD2311 are not yet available, a pre-exposure option, if positioned strategically, may contribute to cost savings as a vaccine alternative for some adults, giving payers and patients more options with next-generation mAbs on the horizon.
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. September 29, 2026. Accessed October 1, 2026.
2. Invivyd announces initiation of DECLARATION clinical trial, a phase 3 placebo-controlled pivotal study of VYD2311, a vaccine-alternative antibody to prevent COVID. News release. Invivyd. December 23, 2025. Accessed October 1, 2026.
3. Invivyd announces receipt of twelve months’ advanced notice of emergency use authorization (EUA) termination for PEMGARDA and provides an update on next steps with the U.S. FDA. News release. Invivyd. July 6, 2026. Accessed October 1, 2026.
4. Santoro C. COVID-19 boosters crucial for patients with cancer despite low uptake. AJMC. July 17, 2025. Accessed October 1, 2026.
5. Joszt L. Economic benefits of broad COVID-19 vaccination in US adults, by age group. AJMC. August 17, 2025. Accessed October 1, 2026.
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