The Phase 3 study looked at the safety and immunogenicity of a single dose of mRNA-1010 during the Southern Hemisphere influenza season: enrolling 6,102 adults across Argentina, Australia, Colombia, Panama and the Philippines.
Influenza A risks
mRNA-1010 encodes for hemagglutinin (HA) glycoproteins of the four influenza strains recommended by the World Health Organization (WHO) to prevent influenza, including influenza A/H1N1, A/H3N2, and influenza B/Yamagata- and B/Victoria-lineages.
Moderna highlights that while both influenza A and B cause seasonal epidemics, influenza A viruses lead to the majority (>95%) of influenza-related hospitalization in adults. The influenza A/H3N2 subtype, in particular, is a significant cause of illness in older adults and is responsible for most of the recent influenza outbreaks and excess morbidity caused by the virus.
The study set out to evaluate non-inferiority to a licensed seasonal influenza vaccine.
The 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.
It enrolled 6,102 adults during the Southern Hemisphere influenza season: with participants randomly assigned to receive either a single dose of mRNA-1010 or a single dose of a licensed vaccine as a comparator.
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.
The vaccine did not, however, meet its endpoints of non-inferiority for the influenza B/Victoria- and B/Yamagata-lineage strains. But Moderna has already updated the vaccine and believes this could improve immune responses against Influenza B. This will be assessed in an upcoming clinical study.
"These results represent an important step forward in the development of mRNA-based influenza vaccines to address the substantial burden of disease caused by influenza. We are encouraged by the safety and tolerability profile, and by the strong immunogenicity results against Influenza A viruses which cause the overwhelming majority of flu-related disease in older adults," said Stephen Hoge, M.D., Moderna's President.
An ongoing mRNA-1010 Phase 3 efficacy study (P302) in Northern Hemisphere countries has accrued more than 200 PCR-confirmed cases (of which 99% are influenza A): with an interim analysis expected in the first quarter of this year.
mRNA-1010 is one of several influenza vaccine candidates being evaluated by Moderna, which include combination vaccine candidates such as one against influenza and SARS-CoV-2 (mRNA-1073), and another candidate against the trio of influenza, SARS-CoV-2, and RSV (mRNA-1230).
Pfizer and BioNTech also have an mRNA influenza vaccine in a similar stage of development, having launched a Phase 3 trial for the candidate in the US in September.