First-generation mRNA vaccines for flu “will not win,” Sanofi executives have admitted as they set out plans to develop more advanced candidates they believe will overcome the technology’s existing shortfalls.
The biggest names in messenger RNA like Moderna, Pfizer and CureVac are all working on their own influenza candidates, but Sanofi used a vaccines investor event yesterday to spell out bluntly why those initial attempts to target the technology on flu just won’t work.
At the event, the French Big Pharma unveiled trial data putting its hemagglutinin-based mRNA vaccine up against the company’s approved quadrivalent flu vaccine Fluzone. In an echo of the underwhelming data posted by Moderna earlier this year for its own candidate, Sanofi’s mRNA shot performed well against influenza strain A but struggled against strain B.
“The immune response we observed with our platform is very similar to that observed with other mRNA vaccines,” Sanofi’s head of translational medicine Saranya Sridhar, M.D., Ph.D., told attendees at the London event. “And what that tells us is that improving on the standard of care, the minimum bar against which all mRNA vaccines need to be compared, is difficult.”
The fact that Sanofi’s competitors are also struggling to tackle B strains “suggests to us that low flu B responses are probably a class effect across mRNA platforms,” Sridhar explained.
“We need to find a more comprehensive solution to ensure a strong B strength performance year on year with mRNA,” he added.
It wasn’t all bad news, however. Sridhar said the Sanofi candidate's strong reaction to A strains and “lower reactogenicity profile compared to competitors” means the Big Pharma has a “competitive mRNA platform.”
Still, as Sanofi’s head of influenza franchise Bill Averbeck put it, “Even if you were to be licensed, this first generation mRNA vaccine will not be commercially successful.”
It may seem like something of an admission of failure for a company that paid $3.2 billion to acquire mRNA-focused Translate Bio two years ago as well as funneling billions more into a highly publicized mRNA strategy. But, while in the near term Sanofi will continue to expand its Fluzone franchise, executives explained that the company will work on a new generation of mRNA flu vaccines, including bringing five different lipids into clinical trials.
So how will these new candidates overcome the shared weakness of mRNA vaccines in tackling B flu strains? For now, Sanofi is remaining tight-lipped on what the underlying issue might be and how to resolve it, citing the “highly competitive field.”
“You have seen that our competitors have not really disclosed what they are working on to fix it,” Thomas Triomphe, Sanofi’s head of vaccines, said. “We believe we have the solution, but we are not going to share that.”
The company isn’t limiting its mRNA tech to flu, either. A therapeutic vaccine for acne is due to enter a phase 1/2 trial in 2023, while an mRNA vaccine for chlamydia is also in the works.
While Sanofi may be reassessing the flu mRNA strategy, things are more straightforward for its respiratory syncytial virus (RSV) ambitions. The Big Pharma has set sights on being the only company to protect all affected age groups from the infection.
With Sanofi preparing for a global launch of its EU-approved immunization for infants, called Beyfortus, starting with this year’s RSV season, plans to initiate a phase 3 trial for a vaccine for toddlers in the first half of 2024 are rolling on, Jean-François Toussaint, Sanofi’s head of vaccines R&D, said.
“If this reads positively in phase 3, there is no doubt that we will deliver the first-in-class RSV vaccine for toddlers, and that we will set a high bar for competitors that are at least two years behind us,” he added.
Toussaint then “shifted gears” to provide an update on Sanofi’s RSV program for older people. Here, there is more competition, with GSK and Pfizer both scoring approvals already this year. However, Sanofi plans to carve out a space in the market by offering a combination mRNA vaccine for this patient group that also addresses the respiratory viruses human metapneumovirus and parainfluenza, with a phase 1/2 trial due to launch by the end of this year.
“Looking at the competitive environment now we believe that our combo vaccine is a real potential to be a first in class,” Toussaint said.
In a reference to the lukewarm response Pfizer and GSK’s RSV candidates received from the FDA’s advisory committee, Toussaint said he expected the combo vaccine’s “superior medical value … will provide a more compelling case to recommending bodies.”