mRNA-1010 Outperforms Standard Flu Vaccine in Phase 3 Trial

Key Takeaways

• In a phase 3 randomized comparison of more than 40,000 adults aged 50 years or older, trivalent mRNA-1010 was tested against a licensed standard-dose influenza vaccine.
• RT-PCR-confirmed, protocol-defined influenza-like illness occurred in 2% of mRNA-1010 recipients and 2.8% of comparator recipients, favoring mRNA-1010.
• Solicited adverse reactions were more frequent with mRNA-1010, particularly injection-site and systemic symptoms.
• Most solicited reactions were mild to moderate and transient, and serious adverse event rates were similar between groups.

Seasonal influenza continues to cause substantial illness in adults aged 50 years or older despite currently available vaccines, leaving open the question of whether a messenger RNA (mRNA) platform built around World Health Organization-recommended strains can improve protection in this age group. mRNA-1010 is an investigational mRNA vaccine encoding hemagglutinin glycoproteins from those strains. In response to that question, adults aged 50 years or older were enrolled in a randomized comparison against a licensed standard-dose influenza vaccine.

In the phase 3 mRNA-1010 influenza vaccine trial in adults aged 50 years or older, 40,703 participants received study vaccine in a double-blind, active-controlled design. Participants were randomly assigned to trivalent mRNA-1010 at 37.5 μg, including 12.5 μg of each strain, or to a licensed standard-dose comparator. The primary efficacy endpoint was relative vaccine efficacy against reverse-transcriptase-polymerase-chain-reaction (RT-PCR)-confirmed, protocol-defined influenza-like illness caused by influenza A or B from at least 14 days after vaccination through the end of the influenza season, with prespecified hierarchical testing for noninferiority and superiority.

After a median follow-up of 181 days (range 1 to 227), relative vaccine efficacy against RT-PCR-confirmed influenza-like illness was assessed in 411 of 20,179 mRNA-1010 recipients (2%) and 557 of 20,124 comparator recipients (2.8%). This corresponded to a relative vaccine efficacy of 26.6% (95% CI 16.7 to 35.4), and the prespecified criteria for noninferiority, superiority, and higher-level superiority were met. The primary endpoint favored mRNA-1010 over the licensed standard-dose comparator in this population.

Solicited adverse reactions were more frequent with mRNA-1010, and most were mild to moderate and transient. Injection-site pain occurred in 65.8% versus 29.8%, and fatigue in 45.1% versus 20.3%; headache and myalgia were also more common with mRNA-1010. Serious adverse events were reported in 2.2% versus 1.9%, and investigators considered three versus two serious events vaccine-related.

The authors concluded that mRNA-1010 was superior to standard-dose licensed vaccines for preventing RT-PCR-confirmed, protocol-defined influenza-like illness in adults aged 50 years or older, while solicited adverse reactions were more frequent.

Clinician Questions

How was influenza illness defined in the mRNA-1010 phase 3 trial?

In adults aged 50 years or older in a phase 3 comparison of trivalent mRNA-1010 with a licensed standard-dose influenza vaccine, the primary outcome was relative vaccine efficacy against RT-PCR-confirmed, protocol-defined influenza-like illness caused by influenza A or B, assessed from at least 14 days after vaccination through the end of the influenza season.

Which adults do the reported mRNA-1010 efficacy results apply to?

The reported efficacy comparison applies to adults aged 50 years or older enrolled in a phase 3, double-blind, active-controlled trial of trivalent mRNA-1010 versus a licensed standard-dose influenza vaccine.

Recommended Reading

• For more on changing influenza vaccine recommendations: Navigating Evolving Influenza Vaccine Guidance
• For more on influenza vaccine safety and benefits: Flu Vaccination During Pregnancy: Evidence and Guidance