Moderna is set to make tens of billions of dollars this year and next from its mRNA COVID vaccine and booster, but the market won’t let the Big Biotech rest on its laurels and wants broader applicability from its programs.
The jury is out as to whether Moderna has delivered some of the potential of that today with some early phase 1 data from its influenza shot trial for mRNA-1010, which only entered the clinic in the July, not showing a clear picture whether it can better newer shots already on the market.
Data from the phase 1 trial, posted in a release Friday morning, showed it “successfully boosted” hemagglutination inhibition assay geometric mean titers (GMTs) against all tested flu strains 29 days after vaccination, at all doses, tested in both younger and older adults.
It has also finished off enrollment in its phase 2 and is prepping for a phase 3 as it adds two new flu candidates, mRNA-1011 and mRNA-1012, to the rota, and will come with additional hemagglutinin (HA) antigens. This may suggest it wants to focus more on a next-gen approach if this one doesn’t pan out so well.
The Cambridge, Massachusetts-based company, made famous by the success of its COVID-19 vaccine, is developing mRNA-1010 to protect against common flu strains as recommended by the World Health Organization.
The company is hoping to improve on traditional flu shots, which are typically about 40% to 60% effective. Most of these shots are developed using eggs, which Moderna said can cause unintended changes to the vaccine virus. The strains to be used in the vaccines are also decided six to nine months ahead of time, meaning a lot of guesswork as to which strain might be dominant during flu season.
The technology works by teaching a patient’s cells to make a protein that can trigger an immune response in the body and spur the creation of antibodies and therefore protection against a virus. While the authorization of the COVID-19 vaccines marked the first time mRNA had been cleared by regulators, the technology has been studied for decades.
Moderna has used mRNA vaccines in trials before, though, aimed at specific flu strains: Back in 2019, it dropped early data from several phase 1 tests showing its mRNA vaccines against H10N8 and H7N9 influenza viruses "were well-tolerated and elicited robust immune responses."
This latest attempt is aiming wider using a seasonal approach that targets multiple strains, including influenza A H1N1, H3N2 and influenza B Yamagata and Victoria. It’s competing with the likes of Pfizer, its mRNA COVID rival, and GlaxoSmithKline to make mRNA work in flu.
In the phase 1 data, mRNA-1010 was assessed at three doses—50 µg, 100 µg and 200 µg—in younger adult (age 18-49) and older adult (age 50-plus) cohorts.
At the lowest dose level (50 µg) in younger adults, Day 29 GMTs against influenza A strains were 538 (H1N1) and 530 (H3N2); GMT against influenza B strains were 467 (B/Yamagata) and 261 (B/Victoria).
Boosts on baseline for influenza A strains were approximately tenfold (H1N1) and eightfold (H3N2), and approximately threefold for B/Yamagata and twofold for B/Victoria. Minimal dose response was observed between the 50-µg, 100-µg and 200-µg dose levels, “suggesting the potential to explore even lower doses.”
At the lowest dose level (50 µg) in older adults, Day 29 GMT against influenza A strains were 310 (H1N1) and 263 (H3N2); GMT against influenza B strains were 305 (B/Yamagata) and 215 (B/Victoria). GMFR for influenza A strains were around sixfold (H1N1) and sixfold (H3N2), and then threefold for B/Yamagata and twofold for B/Victoria. Safety data were generally clean.
The phase 2, made up of 500 patients, and the upcoming phase 3 will be more important in telling us just how efficacious this shot can be, with these early data telling us that the shot is producing some protection.
Shares in the company were off 12% on the data drop in premarket trading Friday morning after a bearish response to the data, which were not as strong as investors had hoped.
Analysts at Jefferies set out the debate. “On one hand, the antibodies increased to good levels, but on the other hand, the levels aren't necessarily seen as high or necessarily better than some high-efficacy vaccines such as Flublok or Fluzone HD,” the analysts said in a note to clients.
“Compared to current flu vaccines, we see this is an improvement vs. some flu vaccines. Current flu vaccines GMT range from low 100's (SNY - Fluzone) to as high as ~400-700. MRNA-1010 was, at minimum, on par with some flu vaccines and better than some (Fluzone - SNY) at the lowest doses (50 µg).”