CureVac and GSK have been racing behind Moderna to try to get the first mRNA flu vaccine to market. But, now, the European partners have come up against the exact same problem as their U.S. competitor when it comes to the “historically challenging” B strains of influenza.
Interim results from an ongoing phase 2 study of the companies’ seasonal influenza candidate showed that the shot “boosted antibody titers against all encoded flu strains and across all age groups and tested dose levels, including the lowest tested dose,” CureVac reported in an April 4 release.
But, while CureVac’s GSK94180-partnered shot was able to beat licensed flu vaccines in triggering an immune response against influenza A strains, the candidate was unable to manage the same feat against strains of influenza B.
Moderna’s flu program ran into the same problem, with a previous version of the U.S. biotech’s mRNA-1010 vaccine failing to meet the non-inferiority threshold for two influenza B strains a year ago. Moderna was later able to bring a new formulation into the clinic that overcame this setback.
CureVac will now also work on “targeted optimizations” to improve the vaccine’s protection against the B strains that will be tested in a separate phase 2 study.
“Immunogenicity for B strains was in line with our expectations also in view of other initial mRNA-based clinical flu development programs,” CureVac Chief Development Officer Myriam Mendila, M.D., said in the release. “We are confident that planned optimizations will improve performance against these historically challenging influenza strains.”
The current phase 2 trial is assessing the vaccine in 480 adults aged 18 to 64 years and another 480 healthy older adults aged 65 to 85, with three dose levels across each age group. In the younger group, immune responses were compared to an approved but unnamed “standard dose seasonal vaccine” while in the older group the responses were compared to a “high dose seasonal flu vaccine,” according to CureVac.
The company said the shot had an “acceptable safety and tolerability profile” with most of the adverse events reported in the week after dosing being either mild or moderate.
“The phase 2 interim data show that CureVac’s highly effective and flexible mRNA technology platform puts us on the right track to advance our joint seasonal influenza vaccine program,” Mendila said.
Despite touting the vaccine’s “strong” results against influenza A strains, the ability to fight off all WHO-recommended strains will be key for CureVac. The WHO recommends protection against the two A subtypes, H1N1 and H3N2, as well as the influenza B Victoria and Yamagata lineages, be included in annual flu shots.
Even if CureVac and GSK can rapidly improve their vaccine’s efficacy against those B strains, they will still be trailing Moderna, which bested GSK’s Fluarix in a phase 3 trial that read out in September 2023. Moderna now has an extension of that study ongoing in older adults and intends to file for approval this year.
Moderna’s mRNA flu ambitions received a shot in the arm last week when Blackstone Life Sciences agreed to provide “up to” $750 million to fund the biotech’s vaccines work, in return for an undisclosed amount of “cumulative” commercial milestone payments and “low-single-digit” royalties on any approved products.