Moderna says non-inferiority endpoint not met for B strains in flu vaccine study

Moderna on Thursday announced interim results from its pivotal Phase 3 safety and immunogenicity trial of mRNA-1010, an mRNA-based seasonal influenza vaccine candidate, in adults. The Phase 3 randomized trial was designed to evaluate the safety and immunogenicity of mRNA-1010 in adults 18 years and older in the Southern Hemisphere. mRNA-1010 encodes for hemagglutinin glycoproteins of the four influenza strains recommended by the WHO to prevent influenza, including influenza A/H1N1, A/H3N2, and influenza B/Yamagata- and B/Victoria-lineages. Interim results indicate that mRNA-1010 achieved superiority on seroconversion rates for A/H3N2 and A/H1N1, as well as superiority on geometric mean titer ratios for A/H3N2 and non-inferiority on geometric mean titer ratios for A/H1N1. Non-inferiority was not met for either endpoints for the influenza B/Victoria- and B/Yamagata-lineage strains. This Phase 3 randomized, observer-blind study was designed to evaluate the safety and immunological non-inferiority of mRNA-1010 to a licensed seasonal influenza vaccine in adults 18 years and older. The trial enrolled 6,102 adults across Argentina, Australia, Colombia, Panama, and the Philippines during the Southern Hemisphere influenza season. Participants were randomly assigned to receive either a single dose of mRNA-1010 or a single dose of a licensed seasonal influenza vaccine as a comparator. mRNA-1010 encodes for hemagglutinin, a major influenza surface glycoprotein considered an important target to generate protection against influenza and is the primary target of currently available influenza vaccines. mRNA-1010 was found to be generally well-tolerated. 70% of mRNA-1010 recipients reported solicited adverse reactions compared to 48% of participants in the active comparator group. A lower rate of SARs was observed in older age groups compared to the younger adult groups. The majority of SARs were grade 1. Pain and axillary swelling were the most common local SARs, and headache, myalgia, and fatigue were the most common systemic SARs reported. No significant differences in unsolicited adverse events, serious adverse events, or adverse events of special interest were observed between the mRNA-1010 and comparator groups. The ongoing mRNA-1010 Phase 3 efficacy study conducted in Northern Hemisphere countries has accrued more than 200 PCR-confirmed cases. Consistent with the predominant circulation of A/H3N2 and A/H1N1 viruses during this influenza season, more than 99% of confirmed cases in the study are caused by influenza A viruses. The first per protocol interim analysis of efficacy is now expected to be reviewed by an independent Data and Safety Monitoring Board before the end of the first quarter. Based on these results the DSMB will notify the Company whether the primary efficacy endpoint has been met or whether the study should continue accruing further cases towards the final analysis.