After initial stumbles, Moderna finally gains clean phase 3 win for mRNA flu shot

After tweaking the formula behind an mRNA flu vaccine, Moderna has finally met all the goals needed for a successful shot in a phase 3 trial. Now, CEO Stéphane Bancel is eyeing a launch as early as 2024. 

An updated version of mRNA-1010 has met all primary endpoints in a phase 3 trial, Moderna said in an announcement Wednesday as part of its annual R&D day. Compared to GSK's Fluarix, Moderna's vaccine showed higher antibody levels for all four influenza strains (two each for influenza A and B) recommended by the World Health Organization (WHO) as well as higher seroconversion rates. Seroconversion is the development of specific antibodies against a virus.

Local and systemic side effects were similar to previously reported mRNA-1010 studies, Moderna said. 

The company expects to meet with regulators very soon and, depending on guidance received, the flu shot could launch as soon as next year, Bancel told Fierce Biotech in an interview. 

“We’ll know more in a few months when we speak to regulators, but [we’re] trying to go as fast as we can,” the CEO said. 

The news is vindication of the decision to update the shot, a move made in February when Moderna revealed that the first version had not met the noninferiority threshold for the two influenza B strains. The WHO recommends protection against two A subtypes, H1N1 and H3N2, as well as two influenza B strains, Victoria and Yamagata, be included in annual flu shots.

For those wondering, no, Bancel isn't willing to share the secret to mRNA-1010's newfound success after the shot initially come up short against the B strains. 

"As you know, several players are trying to make [an] mRNA flu vaccine and we have no intention [of] educating them on how [we came to] to a good outcome,” he said. 

In light of the phase 3 win, an earlier study assessing the efficacy of the first version of the vaccine in the Northern Hemisphere is ending. Moderna said that the study, P302, did not end up accruing enough case numbers by the end of the 2022-23 flu season anyway. By electing not to proceed P302 into another flu season, Moderna hopes to earn an accelerated approval using a surrogate endpoint.

But Bancel has a bigger goal in mind: combining the flu vaccine with other annual shots to create a one-and-done immunization option. He said the focus now is on bringing to market an initial combination vaccine for both flu and COVID-19 with a launch as soon as 2025. A triple combination for COVID, flu and respiratory syncytial virus (RSV) could follow in 2026.

Meanwhile, a biologics licensing application for a solo RSV vaccine in older adults has been submitted to the U.S. and other global regulators, with an FDA decision deadline expected for April 2024. Pfizer and GSK had their candidates approved for certain adult populations this year. 

Moderna has maintained that a combination of two or three of its shots will be exactly what the doctor ordered—maybe literally—for adults looking for a more efficient way to get vaccinated. The company does not plan on running an efficacy trial for its combination shots, citing regulator guidance that studies on combination vaccines just need to prove safety and tolerability so long as each individual vaccine has been approved as efficacious. Bancel said payers and governments are particularly enticed by the prospect of improving vaccine compliance. 

Elsewhere in the company’s vaccine pipeline, a phase 3 study testing a vaccine for cytomegalovirus is now fully enrolled. Bancel was cautious to provide guidance on an interim readout given that the trial has to accrue cases but said he “would be surprised if it was less than a year from now.” 

“I’m not worried about [if] our technology [is] going to work ... it’s just do you get the right particle effect given it's a complex virus,” he said. 

Work is continuing on vaccines for Lyme disease and Zika virus, Bancel said. Discussions are underway with regulators regarding a phase 2 safety trial for the latter, but the hope is that the FDA will OK an approval pathway using antibody levels in animals. As for mpox, Bancel stuck by a previous statement that it's not a high priority, and thus Moderna won't rush into a phase 3 trial—though he's committed to a phase 1/2 study. 

"The piece we have to be thoughtful [of] … is is it something that the world needs or not? And is it worth us run[ning] a phase 3 or not if [there's] a product equivalent on the market and the outbreak is finished?" he said.