Moderna checks a few boxes in phase 3 mRNA flu shot trial, but misses on B strains and safety

Moderna had high hopes for its first seasonal flu vaccine to enter the clinic, but, so far, the mRNA shot hasn't quite lived up to the hype. While the vaccine checked off two influenza A strains in a phase 3 trial, it struggled against two B strains in the same test and had a higher level of adverse events than an approved flu shot.

In interim results from the late-stage study posted Thursday afternoon, Moderna found that mRNA-1010 was superior to an approved vaccine in creating antibodies against the A/H3N2 and A/H1N1 strains. The shot also was superior in antibody levels against the A/H3N2 strain and equal to the approved shot for A/H1N1.

But Moderna’s vaccine did not match the approved shot on the influenza B/Victoria- and B/Yamagata-lineage strains. Back in 2021, Moderna said that the candidate boosted protection against all strains. 

"While we did not achieve non-inferiority for the influenza B strains which are more frequent in younger populations, we have already updated the vaccine that we believe could improve immune responses against influenza B and will seek to quickly confirm those improvements in an upcoming clinical study thanks to the agility of our mRNA platform," Moderna President Stephen Hoge, M.D., said in the release.

A high rate of solicited adverse reactions was reported in those who received mRNA-1010, with 70% of recipients experiencing an event compared to 48% in the comparator arm. Events, which included pain and swelling, headache and fatigue, were lower in older adults and higher in younger recipients of Moderna’s shot. The company said that mRNA-1010 was “generally well-tolerated.”

Moderna is trying to improve upon seasonal flu shots, which currently boast an efficacy rate of 40% to 60% depending on how well matched the yearly jabs are to the circulating strains. Its mRNA-1010 is one of five mRNA shots in consideration by the company, made famous by its work to develop the COVID-19 vaccine Spikevax.

The trial enrolled 6,102 adults over 18 to determine the safety and immunological noninferiority of the mRNA vaccine when compared to a licensed seasonal flu shot. Moderna’s vaccine goes after the same target as traditional vaccines, a glycoprotein called hemagglutinin. This study was conducted in the Southern Hemisphere, while a similar trial is also being conducted in the Northern Hemisphere and has reached 200 confirmed cases. Moderna said most of those cases have been influenza A viruses, which is consistent with the currently circulating strains this year.

The company expects the independent data and safety monitoring board to conduct an interim analysis of this study before the end of the first quarter, at which point they will decide whether the primary endpoint has been met or whether the trial needs to continue on for more data.

Influenza A viruses lead to 95% of influenza-related hospitalizations in the U.S., Moderna noted. According to the Centers for Disease Control and Prevention, currently approved vaccines contain protection against the two A subtypes, H1N1 and H3N2, as well as the influenza B Victoria and Yamagata lineages. The World Health Organization recommends all four strains be included in annual flu shots.

Moderna got its trials for mRNA-1010 underway in June 2022, while its peers in the COVID-19 race Pfizer and BioNTech kicked off a phase 3 of their own mRNA flu candidate in September. Coming up from behind are Sanofi—which laid claim to having entered the first mRNA flu vaccine into the clinic via a partnership with Translate Bio—as well as GSK, which has a collaboration with CureVac.