mRNA-Flu(National Institute For Health & Care Research/Acuitas Therapeutics)

A spokesperson told Fierce Biotech this morning that it is not yet able to set out a timeline for when the vaccine will enter phase 3. After an initial defeat against the biggest barrier to mRNA flu vaccines—namely, B strains of influenza—GSK has returned with a reformulated candidate that has delivered the goods in the all-important population of older adults.The British pharma already demonstrated in a previous phase 2 trial in April that its candidate was able to beat licensed flu vaccines when it came to triggering an immune response against influenza A strains. But the company had to admit that it couldn’t manage the same feat against “historically challenging” B strains of influenza.CureVac, which had been developing the vaccine with GSK, said at the time that they would work on “targeted optimizations” to improve the shot’s protection against the B strains, and it seems like that has finally done the trick. GSK has returned Wednesday morning with fresh phase 2 data that show new formulations of the vaccine “demonstrated positive A and B strain immune responses relative to standard of care in both younger and older adults.”The study enrolled 250 healthy adults aged 18 to 64 years and another 250 aged 65 to 85 years. The companies tested a range of mRNA formulations and dose levels of their own vaccine against age-appropriate, approved flu shots, showing that their candidate induced acceptable immune responses for both A and B strains.Interim data also suggest the various formulations tested had “an acceptable safety and reactogenicity profile,” GSK said.The Big Pharma bought out the full rights to CureVac’s flu and COVID mRNA candidates for $430 million in July. Today’s results “confirm the mRNA platform elicits strong overall antibody titres with an acceptable safety profile,” said GSK, which will now move its vaccine into phase 3. “This marks a significant advancement in our mRNA programme and these data support moving into late-stage development,” GSK Chief Scientific Officer Tony Wood, Ph.D., said in the Sept.12 release. “Ultimately, our goal is to develop a new best-in-class vaccine to bring greater protection to people through the influenza season.”A spokesperson told Fierce Biotech this morning that the company is not yet able to set out a timeline for when the vaccine will enter phase 3, but further updates will be provided at the next quarterly earnings.GSK’s peers in the race to get the first mRNA flu vaccine to market have all encountered the same problem when it comes to B strains. Moderna is the only competitor to have already secured full success—showing a year ago that a reformulated version of its candidate was able to induce higher antibody levels for major B strains than GSK’s approved flu vaccine Fluarix in a phase 3 trial.Meanwhile, Sanofi’s executives were so disheartened by the failure of their own candidate to neutralize B strains that they proclaimed last year that the first generation of mRNA vaccines for flu “will not win.”Pfizer and BioNTech have managed to overcome B strains with their own mRNA candidate in a phase 3 study—but so far only against under-65s. The companies revealed last month that their combo COVID-flu mRNA vaccine didn’t manage to neutralize B strains in older adults.Like Pfizer, GSK also has plans to work on its own COVID-flu combination vaccine, and today’s results should ease the path toward that development.

Pfizer and BioNTech can take some comfort from the fact that their mRNA peers have also struggled to tackle influenza strain B. Pfizer and BioNTech may have a strong pedigree in the mRNA vaccine game, but, when it comes to flu, they’ve run up against the same problem as their peers—neutralizing influenza strain B.The two companies have been testing a combination flu and COVID-19 vaccine in a phase 3 trial. While the candidate did demonstrate sufficient immunogenicity against SARS-CoV-2 when compared to the companies’ own approved COVID-19 vaccine Comirnaty, it failed the trial’s other primary endpoint of triggering an immune response against both influenza strains A and B when compared to an unnamed approved flu shot.“Compared to a licensed influenza vaccine, the [trivalent] formulation was noteworthy for eliciting robust influenza A responses, including a continued trend of higher influenza A responses versus a licensed influenza vaccine, while it showed lower geometric mean titers and seroconversion against the influenza B strain,” the two companies noted.The study enrolled more than 8,000 adults ages 18 to 64, and the companies said no safety signals related to its combo vaccine were identified in an ongoing safety data review. Pfizer and BioNTech are now “evaluating adjustments” to the combo candidate, which consists of Comirnaty and an mRNA flu vaccine that Pfizer has been working on.“We are dedicated to developing combination vaccines which provide broader protection against multiple respiratory diseases,” BioNTech CEO Ugur Sahin, M.D., said in the release.“The insights gained from this combination vaccine trial are highly valuable and will play a crucial role in guiding the further development of Pfizer’s and our combination vaccine program against influenza and COVID-19,” Sahin added. “We are committed to drawing on our experience in developing mRNA-based vaccine candidates against multiple antigens and believe we can successfully accomplish this task in collaboration with our partner Pfizer.”Annaliesa Anderson, Ph.D., senior vice president and head of vaccine R&D at Pfizer, said the Big Pharma “remains optimistic” about the combo vaccine while it is “evaluating the next steps.” Perhaps the companies can take some comfort from the fact that their mRNA peers have also struggled to tackle influenza strain B. A previous version of Moderna’s mRNA-1010 vaccine failed to meet the noninferiority 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.More recently, CureVac and GSK’s mRNA flu vaccine came up short against “historically challenging” B strains, leading the partners to work on “targeted optimizations” to improve the vaccine’s protection against these strains.Meanwhile, Sanofi’s executives were so disheartened by the failure of their own candidate to neutralize B strains that they proclaimed last year that the first generation of mRNA vaccines for flu “will not win.”Judging by Pfizer’s other piece of news today, Sanofi may be proved right. In this morning’s release, Pfizer also revealed that a phase 2 trial of its next-gen trivalent mRNA flu formulations “elicited robust influenza A responses and B responses, including continued trend of higher influenza A responses versus a licensed influenza vaccine” in adults ages 18 to 64.The Big Pharma didn’t go into more detail and said a top-line readout from the trial for adults ages 65 years and over would only be unveiled “at a later date.”A phase 3 trial of Pfizer’s original quadrivalent mRNA influenza candidate already secured success against B strains among people younger than 65, the pharma pointed out in today’s release, but couldn’t manage the same feat in older patients.