Moderna says its mRNA flu vaccine cleared early studies, but comparisons with other vaccines drive stock down
Moderna says that it’s on its way to having an mRNA vaccine against not one, but two different seasonal viruses.
The biotech released the first early data from its flu program Friday morning, announcing that all doses of the shot significantly boosted antibodies in younger and older adults without “significant safety findings.”
A 500-person Phase II will confirm dose levels and compare it to an approved flu vaccine, the company said, and preparations for a large pivotal trial are underway. Moderna said it is also advancing new designs that can have potentially broader coverage of different flu strains than current shots.
The results are the opening salvo in a four-headed (so far) race to develop the first mRNA flu vaccine, as Moderna tries to edge out BioNTech, Sanofi subsidiary Translate Bio, and CureVac past the gate. Although all four have programs underway, Moderna is the first to announce data.
Those data, though, don’t give a clear answer on whether mRNA can improve on previous technologies. Moderna said the 50 microgram dose of the shot, designed like most flu vaccines to inoculate against four different strains of the virus, increased antibodies against the two Influenza A strains by eight-fold and ten-fold, respectively, and against the two influenza strains by three-fold and two-fold.
There was little difference in antibodies between dose levels, the company said. Safety data echoed those from the Covid-19 vaccine, with fatigue, myalgia (muscle ache), and headache the most common side effects.
The company hopes it will eventually be approved and then combined with its Covid-19 vaccine, and its experimental RSV shot for a single seasonal virus vaccine.
Outside experts praised the data, but were cautious about how big an impact the single shot will have, especially given Moderna’s promise of “premium pricing.”
“It looks very good,” Adolfo García-Sastre, director of the Center for Research on Influenza Pathogenesis, said in an email.”There are many approved flu vaccines. I think if approved, this will be just one more.”
Analysts also raised questions about what the side effect profile could mean for the potential combo vaccine. SVB Leerink’s Mani Foroohar noted there were significantly more grade 3 side effects than in other flu vaccines.
Combining that with a Covid-19 booster and an RSV booster could potentially make a shot that’s too reactogenic to be widely used.
Should Moderna “go back to the drawing board?” Foroohar asked on a conference call.
Moderna president Stephen Hoge cautioned against making comparisons between shots before head-to-head trials came out.
Companies working on mRNA vaccines have long believed mRNA flu shots could be more potent and manufactured faster than existing flu vaccines, allowing developers to more closely match up the strains in the shot with the strains circulating in a given season.
On the conference call Friday morning, Hoge estimated the flu vaccine market at $11 billion. He said the company could cut significantly into that market by being able to closely match circulating strains, citing data that suggest in some years flu vaccine efficacy drops as low as 19%.
He particularly noted the impact of variation in H3N2 on vaccine efficacy.
“This, we think, represents one of the most significant opportunities for improving vaccine efficacy,” he said.
But the company’s own data on antibodies comparing their shot to a different trial to Sanofi’s approved protein-based flu vaccine Fluzone found the results were largely similar. CEO Stéphane Bancel focused instead on strain-matching and the potential for a two-in-one or three-in-one vaccine.
“We believe Moderna can be the first company to market a vaccine for covid-plus-flu,” he said.
Jefferies analyst Michael Yee said the data were “promising” and “somewhat in line with our expectations,” but he acknowledged the comparison data leave room for debate. “There is going to be debate on whether it’s truly better than newer high-efficacy vaccines from [Sanofi],” he said.
As Sanofi CEO Paul Hudson has argued, because there are already established shots, the bar for approval and widespread adoption in flu may be higher than it was for Covid-19. And not all vaccinologists agree that mRNA is a good match for flu, especially given their harsher side effects.
“They only give short-lived immunity to COVID (less than 6 months) after two doses, with more side effects than a regular flu shot,” Hildegund Ertl, a vaccinologist at the Wistar Institute who focuses on adenovirus vaccines, said in an email. “They did a great job with the pandemic but I don’t see them as a long-term solution for seasonal viruses.”
Millions of dollars, though, are being spent on the idea that mRNA can replace existing flu shots entirely. Pfizer is helping BioNTech’s efforts and GSK has signed onto CureVac’s.
Investors and infectious disease experts will closely compare today’s data with early results out of ongoing Phase I trials from BioNTech and Translate in the coming months. For now, the investors appear largely bearish.
Moderna $MRNA is down 12% premarket.