Phase 3 Trial of Combination Flu/SARS-CoV-2 Vaccine Meets All Primary Endpoints: Moderna

The phase 3 trial of the investigational combination vaccine against influenza and SARS-CoV-2 in development by biopharmaceutical company Moderna met all primary endpoints, according to a company announcement, with mRNA-1083 eliciting a higher immune response vs all licensed comparator vaccines used in the trial.

In October, the company announced that the first participant had been dosed in the ongoing phase 3 study that has enrolled approximately 8000 individuals. The randomized, observer-blind, active control clinical trial is evaluating the immunogenicity, safety, and reactogenicity of mRNA-1083 across 2 independent age‐group substudy cohorts of approximately 4000 individuals aged 65 years and older and 4000 individuals aged 50 to 64 years.

In the former subgroup, mRNA-1083 was compared to coadministered enhanced influenza vaccine, Fluzone HD (Sanofi) and in the latter to a standard dose of the influenza vaccine, Fluarix (GSK). For both age groups, mRNA-1083 was compared to a standard dose of Moderna’s Spikevax COVID-19 bivalent booster shot.

FINDINGS

Moderna investigators found that a single dose of the investigational mRNA-1083 elicited immune responses that were noninferior compared to the coadministered and routinely recommended licensed comparator vaccines. Across the 2 age cohorts mRNA-1083 resulted in higher immune responses that were statistically significant against 3 influenza virus strains and against SARS-CoV-2, according to Moderna. In the older adult cohort, overall geometric mean ratios (GMR) among those treated with mRNA 1083 vs those treated with Fluzone HD for the 3 flu strains were 1.0 or greater. The combination vaccine's GMR compared with Spikevax for the SARS-CoV-2 Omicron variant XBB.1.5 was greater than 1.5, as stated in the announcement.

Although the B/Yamagata strain of influenza is no longer in circulation and will not be included in the 2024/2025 vaccines, the immunogenicity of mRNA-1083 was evaluated against it in the phase 3 trial and met the noninferiority criteria for both age groups, according to Moderna.

Moderna reported an acceptable safety and tolerability for mRNA-1038, stating the majority of solicited adverse reactions were rated grade 1 or 2 in severity and were consistent with profiles of the licensed vaccines administered in the trial. They included injection site pain, fatigue, myalgia, and headache.

The company plans to present the phase 3 data for the dual vaccine at an upcoming scientific conference and also submit them for publication in a peer-reviewed journal.

"Combination vaccines have the potential to reduce the burden of respiratory viruses on health systems and pharmacies, as well as offer people more convenient vaccination options that could improve compliance and provide stronger protection from seasonal illnesses," Stéphane Bancel, Moderna CEO said in the press announcement.

"Moderna is the only company with a positive Phase 3 flu and COVID combination vaccine. Building on the momentum of positive Phase 3 data across our respiratory portfolio, we continue to address significant unmet medical needs and advance public health."