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Moderna Announces Withdrawal of BLA for Flu/COVID-19 Combination Vaccine
Moderna voluntarily withdrew the BLA after consultation with the FDA and will resubmit once it has additional phase 3 efficacy data for its investigational flu shot.
Moderna announced on Wednesday that the company has withdrawn the pending Biologic License Application for mRNA-1083, its influenza/COVID-19 combination vaccine candidate for adults aged 50 years and older. The decision was voluntary and made in consultation with the FDA, according to a company statement.1
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Moderna filed for approval of the investigational combination shot last year and appeared to be on track for an FDA decision in November of this year. On May 1 the company reported feedback from the agency requesting additional efficacy data from an ongoing phase 3 trial of mRNA-1010, Moderna's investigational seasonal influenza vaccine.2 That interim data is still expected to be available this summer, the company said. Once the subsequent analysis is complete, Moderna will resubmit the BLA. The company has pushed back an expected approval date for mRNA-1083 to 2026.1
Less than 2 weeks ago, the company reported immunogenicity data on the combination vaccine demonstrating its noninferiority to individual shots for both of the infections. Findings from the study were published online in JAMA.3
On an earnings call in early May, Stephen Hoge, MD, Moderna’s president, discussed the FDA’s request for efficacy data from the 40,000-person study of the solo flu vaccine. “It makes good scientific sense that that would be a part of the review that's going on for our flu-COVID combination.” At the time, Moderna was unsure whether it would opt to resubmit the filing, according to reporting by Fierce Biotech.4
mRNA Phase 3 Trials
In June 2024, the company announced initial findings from the randomized, observer-blind, active control clinical trial evaluating the immunogenicity, safety, and reactogenicity of mRNA-1083. The study includes 2 independent age‐group cohorts of approximately 4000 individuals aged 65 years and older and 4000 individuals aged 50 to 64 years.5
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.5
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. 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 1.5.5
The safety and immunogenicity findings reported earlier this month are from the planned interim analyses after all participants had completed the day 91 visit. Immunogenicity data are reported from days 1 and 29. Data from the final analysis (through the day 181 visit) will be reported separately.3
The assessment of immunogenicity showed that mRNA-1083 achieved noninferiority against all vaccine-matched influenza and SARS-CoV-2 strains based on strict statistical criteria - specifically, the lower bound of the 97.5% confidence interval of the geometric mean ratio greater than 0.667 and the lower bound of the 97.5% confidence interval of the seroconversion/seroresponse rate difference greater than -10%.3
Vaccine Regulatory Landscape
Vaccine regulation at the FDA has been disrupted with the arrival of the new administration and significant changes in leadership at the Department of Health and Human Services (HHS). Recently HHS announced that all new vaccine trials are required to include a full placebo arm.6 A more specific requirement was announced for COVID-19 vaccines on May 20 in an unusual commentary published in the New England Journal of Medicine. Coauthored by FDA Commissioner Marty Makary, MD, MPH, and CBER Director Vinay Prasad, MD, MPH, the statement announced that FDA will now approve updated SARS-CoV2 vaccines primarily for high-risk populations, ie, people aged 65 years and older and individuals aged 6 months and older with risk factors for severe illness.7 Vaccine manufacturers will now be required to mount new clinical trials to demonstrate benefit before the agency will authorize boosters for healthy individuals in the general population under age 65.7
