Moderna Withdraws BLA for Combination Influenza and COVID-19 Vaccine

By IDSE News Staff

After consulting with the FDA, Moderna voluntarily withdrew its pending Biologics License Application (BLA) for mRNA-1083, an influenza−COVID-19 combination vaccine candidate. The company was seeking an indication for adults ages 50 years and older.

The company plans to resubmit the BLA later this year, after vaccine efficacy data from the ongoing phase 3 trial of its investigational seasonal influenza vaccine, mRNA-1010, are available, which are expected this summer.
In June 2024, Moderna announced that mRNA-1083 elicited a higher immune response than the licensed comparator vaccines used in its phase 3 trial.

The composition of mRNA-1083 consists of mRNA-1010 and mRNA-1283, Moderna's next-generation COVID-19 vaccine candidate. Each investigational vaccine has independently demonstrated positive phase 3 clinical trial results.

A phase 3, randomized, observer-blind, active control study evaluated the safety, reactogenicity and immunogenicity of mRNA-1083 in two independent age groups of just over 4,000 adults each (ClinicalTrials.gov Identifier:NCT06097273). One cohort, consisting of adults 65 years and older, compared mRNA-1083 with coadministered Fluzone HD (Sanofi), high-dose influenza vaccine, and Spikevax, Moderna's currently licensed COVID-19 vaccine. The other cohort of adults 50 to 64 years of age compared mRNA-1083 with coadministered Fluarix (GSK), a standard-dose influenza vaccine, and Spikevax.

The immune responses from a single dose of mRNA-1083 were noninferior to the routinely recommended, licensed comparators. In both age cohorts, mRNA-1083 also elicited statistically significantly higher immune responses against three influenza virus strains (H1N1, H3N2 and B/Victoria) and against SARS-CoV-2 (JAMA 2025 May 7:e255646. doi:10.1001/jama.2025.5646). 

In the 65 years-and-older cohort, overall geometric mean ratios (GMRs) of the mRNA-1083 group compared with the Fluzone HD group for the influenza strains were 1.155 (95% CI, 1.094-1.220) for A/H1N1, 1.063 (95% CI, 1.007-1.122) for A/H3N2, and 1.118 (95% CI, 1.070-1.167) for B/Victoria. The GMR of mRNA-1083 compared with Spikevax for the SARS-CoV-2 variant Omicron XBB.1.5 was 1.641 (95% CI, 1.526-1.765). In the 50-to-64 years of age cohort, the GMRs of the mRNA-1083 group compared with the Fluarix group for the influenza virus strains were 1.414 (95% CI, 1.333-1.500) for A/H1N1, 1.380 (95% CI, 1.310-1.454) for A/H3N2, and 1.216 (95% CI, 1.163-1.270) for B/Victoria. The GMR of mRNA-1083 compared with Spikevax for the SARS-CoV-2 variant Omicron XBB.1.5 was 1.308 (95% CI, 1.219-1.404).

Immunogenicity was also tested against the B/Yamagata strain of influenza and mRNA-1083 met noninferiority criteria in both age cohorts. However, B/Yamagata is no longer a component of today’s influenza vaccines because it has disappeared from circulation.

Tolerability and safety of mRNA-1083 were shown to be acceptable. Most adverse reactions were grade 1 or 2 in severity and consistent with the licensed vaccines used in the trial. The most commonly seen adverse reactions were injection site pain, fatigue, myalgia and headache.

“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,” said Stéphane Bancel, the CEO of Moderna, in an announcement of the results.

Earlier this year, Moderna announced ongoing support from the Department of Health and Human Services (HHS) to accelerate the development of mRNA-based pandemic influenza vaccines. 

The project will provide additional support for late-stage development and licensure of pre-pandemic mRNA-based vaccines. The agreement will also support the expansion of clinical studies for up to five additional subtypes of pandemic influenza.

In 2023, Moderna initiated a phase 1/2 study to generate safety and immunogenicity data for an investigational pandemic influenza vaccine (mRNA-1018) in healthy adults ages 18 years and older. The study included vaccine candidates against H5 and H7 avian influenza viruses. This $590 million award has been funded in whole or in part with federal funds from HHS, the Administration for Strategic Preparedness and Response, the Biomedical Advanced Research and Development Authority, and the Rapid Response Partnership Vehicle Consortium.