Moderna's mRNA flu shot struggles to prove its worth again in phase 3 trial

Moderna’s first seasonal flu vaccine continues to underwhelm with the mRNA giant revealing that the shot hasn’t yet been able to prove success in an interim analysis of an ongoing phase 3 trial.

The vaccine, dubbed mRNA-1010, “did not meet the statistical threshold necessary to declare early success” due to a lack of “sufficient cases” at the interim analysis of a late-stage trial in the northern hemisphere, Moderna revealed in a pipeline update Tuesday morning.

While not identifying any safety concerns, the independent Data and Safety Monitoring Board recommended the trial continue “with efficacy follow-up towards the next analysis,” the company said.

A preliminary analysis of immunogenicity from a subset of participants in the trial has also been completed, which showed that mRNA-1010 demonstrated geometric mean titer ratios suggesting it was more effective against both influenza A strains than an approved flu vaccine. However, when it came to both influenza B strains, the shot was only able to show “non-inferiority” to the competitor, Moderna said.

That analysis mirrored results from a separate phase 3 trial in the southern hemisphere, which showed in February that while the vaccine scored a hit on two influenza A strains in a phase 3 trial, it struggled against the B strains. It’s an issue for a potential vaccine that Moderna hailed back in 2021 as boosting protection against all strains. 

To counter this weakness against influenza B, Moderna confirmed today that it has developed an update to mRNA-1010 that is expected to offer improved immunogenicity against the B strains, with a confirmatory phase 3 trial due to launch this month.

Judging by comments from Moderna’s top brass back in February, the company was braced for the possibility that mRNA-1010’s efficacy wouldn’t be demonstrated at the interim analysis. “If we do not yet meet that threshold, then we'll be looking forward to subsequent interim analyses in that study,” Moderna President Stephen Hoge, M.D., said in the company’s fourth-quarter earnings call that month.

“Many of the currently approved influenza vaccines have, in the past missed on noninferiority for an influenza B strain endpoint here or there and still have received full approval or accelerated approvals,” Hoge said on the same call.

It’s unclear whether investors still share Hoge’s optimism, with Moderna’s shares falling 6.46% to $149.80 in the opening hour of trading Tuesday morning from a Monday closing price of $160.15.