Moderna Withdraws BLA For its Influenza COVID-19 Combination Vaccine
The company made the decision after the FDA requested more vaccine data for the mRNA-1083 vaccine. Moderna plans to resubmit their Biologics License Application (BLA) for the vaccine later this year.
Image credit: Moderna
Moderna announced today it has voluntarily withdrawn the pending BLA for its influenza/COVID-19 combination vaccine candidate, mRNA-1083. The late-stage vaccine was indicated for adults aged 50 years and older.1 This withdrawal comes after the FDA had requested that Moderna provide more data for its vaccine. Specifically, the federal agency requested more phase 3 influenza efficacy data.2
The FDA request came earlier this month, and based on the agency’s feedback, Moderna expected an extended review timeline.2 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. Moderna continues to expect interim data from the mRNA-1010 trial to be available this summer.1 The company is now targeting FDA approval in 2026.
Phase 3 Data
The phase 3 trial is a randomized, observer-blind, active control study evaluating the safety, reactogenicity, and immunogenicity of mRNA-1083 in two independent age group cohorts of approximately 4000 adults each. One cohort, consisting of adults 65 years and older, compared mRNA-1083 to co-administered Fluzone HD, an enhanced influenza vaccine, and Spikevax, Moderna's currently licensed COVID-19 vaccine.3
The other cohort of adults 50 to 64 years of age compared mRNA-1083 to co-administered, Fluarix, a standard dose influenza vaccine, and Spikevax. The immune responses from a single dose of mRNA-1083 were found to be non-inferior versus the co-administered, routinely recommended, licensed comparators.3
In both age cohorts, the Moderna vaccine also elicited statistically significantly higher immune responses against 3 influenza virus strains (H1N1, H3N2, and B/Victoria) and against SARS-CoV-2. In the 65 years and older cohort, overall Geometric Mean Ratios (GMRs) of the mRNA-1083 group compared to 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 to Spikevax for the SARS-CoV-2 variant Omicron XBB.1.5 was 1.641 (95% CI: 1.526, 1.765).3
In the 50 to 64 years of age cohort the GMRs of the mRNA-1083 group compared to 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 to Spikevax for the SARS-CoV-2 variant Omicron XBB15 was 1.308 (95% CI: 1.219, 1.404).3
Comparing mRNA-1083 to Other Vaccines
Separately, the mRNA-1083 vaccine was shown to be noninferior in comparison to other vaccines, elicited better immune responses than standalone influenza and COVID-19 vaccines, and performed better against all influenza strains and SARS-CoV-2 in adults aged 50 and older.4
This was a randomized, observer-blinded, active-controlled phase 3 study carried out in 146 sites exclusively in the US. It was divided into 2 different aged cohorts: individuals 65 years and older; and people 50-64 years old. In a substudy, those 65 years and older was also stratified into those aged 65 to 74 years or 75 years and older. 1
The study enrolled and vaccinated 8015 individuals. The data from this study provided safety and immunogenicity findings of the planned interim analyses after all participants had completed the day 91 visit. 1
“mRNA-1083 contained 5 mRNA sequences encoding membrane-bound hemagglutinin of 4 influenza strains (recommended for Northern Hemisphere 2023-2024 season) and the linked NTD-RBD of the SARS-CoV-2 S glycoprotein (Omicron XBB.1.5), encapsulated in lipid nanoparticles,” the investigators wrote. 4
Individuals were administered either the mRNA-1083 vaccine, or 1 of 2 standalone influenza vaccines plus a COVID-19 vaccine. 4
“mRNA-1083 increased hemagglutination inhibition and PsVNA GM antibody levels against each influenza (A/H1N1, A/H3N2, B/Victoria, B/Yamagata) and SARS-CoV-2 strain at day 29 vs baseline…The primary immunogenicity objective was achieved in both substudies. Noninferiority of mRNA-1083 vs SD-IIV4 plus mRNA-1273 and HD-IIV4 plus mRNA-1273 was demonstrated against all vaccine-matched influenza and SARS-CoV-2 strains based on prespecified success criteria for GMR (97.5% CI lower bound >0.667) and seroconversion/seroresponse rate difference (97.5% CI lower bound >−10%),” the investigators wrote.4
