Phase 3 Trial Finds Adding Monoclonal Antibody to mRNA Vaccine Improves COVID-19 Immunization Tolerability

In an interview with Pharmacy Times, Michael Mina, MD, PhD, Chief Medical Officer and Chief Epidemiologist, Invivyd, discussed findings from the phase 3 LIBERTY study, which he described as the first randomized, placebo-controlled trial to compare 2 distinct SARS-CoV-2 immunizing modalities head-to-head and in combination.

The trial randomly assigned 210 participants equally to receive an mRNA COVID-19 vaccine, VYD2311 (Invivyd's next-generation monoclonal antibody), or both concurrently, with all arms placebo controlled to maintain blinding. Rather than evaluating clinical efficacy, the study assessed safety, tolerability, and immunologic response, including whether monoclonal antibody administration might interfere with vaccine-induced immunity.

According to Mina, treatment-emergent adverse events (TEAEs) occurred in 91.4% of participants in the mRNA vaccine arm compared with 56% in the monoclonal antibody arm. He noted that the vaccine arm's rate closely mirrored rates previously reported for mRNA vaccines in Sanofi's COMPARE study, reinforcing confidence in the findings. Systemic adverse events, such as chills, fever, and fatigue, during the first 6 days occurred in 68% of vaccine recipients vs 44% of monoclonal antibody recipients.

Mina highlighted a surprising finding: participants who received the combination experienced fewer TEAEs and systemic adverse events than those who received the vaccine alone. He explained that this result is consistent, in retrospect, with how the 2 modalities work, and suggested it may open new avenues to strengthen protection while improving vaccine tolerability.

For pharmacists, who administer a substantial share of COVID-19 vaccines and routinely counsel patients on postvaccination adverse effects, these data may be relevant when addressing hesitancy rooted in concerns about reactogenicity. Although the LIBERTY study was not designed to assess clinical efficacy, its findings suggest monoclonal antibodies could serve as a well-tolerated option, alone or alongside vaccination, as the COVID-19 immunization landscape continues to evolve.