- Moderna's plans to develop a messenger RNA vaccine covering several common influenza strains took a step forward Friday, when the company announced results from a small, early-stage study testing its shot in 180 healthy adults.
- Data showed the vaccine spurred immune responses against four widely circulating flu strains, with no worrisome safety findings that would derail further testing. A Phase 2 trial of the shot is already enrolled, with data expected early next year that could give a better sense of its potential.
- While Moderna characterized the results as encouraging, they also appeared to have given some investors pause as shares in the biotech fell by as much as 14% Friday morning. The immune responses observed, for instance, didn't appear significantly greater in older adults than an already available vaccine from Sanofi. And while few severe side effects were reported, mild to moderate reactions like fatigue, muscle pain and headache were more common.
Having proved messenger RNA's might as a vaccine technology for COVID-19, Moderna aims to prove it can work better than existing shots for countering seasonal influenza and, eventually, other respiratory infections.
The results disclosed Friday are the first look at a vaccine Moderna designed in January and put into human testing only five months ago, a timeline that showcases the speed at which mRNA shots can be developed.
Yet, initial data appear somewhat mixed. They indicate that the vaccine can spur desired immune responses to the strains it's designed to combat, but also raise questions of whether it can outperform other options.
The shot, dubbed mRNA-1010, is constructed similarly to Moderna's vaccine for COVID-19, wrapping a strip of genetic code in a fatty bubble that, once injected into the blood, coaxes cells to produce a protein found on the surface of the target virus.
In the case of influenza, that protein is called hemagglutinin and is the main target for available flu vaccines. Yet it shapeshifts often and can vary across flu subtypes that may be more or less prevalent in any given year. Typically, current vaccines are anywhere from 40% to 60% effective against the circulating flu strain, a mismatch that in part reflects the months of lead time that manufacturers need to prepare each year's vaccine.
Moderna thinks mRNA could be a more flexible system, allowing the company to design and adapt its shot closer to flu season, when scientists are more confident in which strain might predominant.
For the Phase 1 study, Moderna designed a vaccine for four strains singled out by the World Health Organization: H1N1, H3N2 and two influenza B subtypes known as Yamagata and Victoria.
Three doses — 50 micrograms, 100 micrograms and 200 micrograms — were tested in groups of 45 study participants each and compared to a fourth group that received placebo.
Unusually, higher doses did not appear to lead to significantly higher immune responses, but did result in more frequent reactions, leading Moderna to focus on the 50 microgram dose, which it will also test in Phase 2.
Twenty-nine days after the 50 microgram shot, antibody levels against H1N1 and H3N2 had risen by 10-fold and 8-fold, respectively in adults aged 18 to 49, and by 6-fold for each in adults over 50. The immune response against the two influenza B strains was less, with antibody rises of 3-fold and 2-fold for Yamagata and Victora, respectively, in both age groups.
"It is a bit of a mixed picture and strain specific," said Moderna President Stephen Hoge in a conference call Friday. "We have to be careful about over interpreting" the data, he added, citing the small number of patients in the study.
Among older adults, the titer, or antibody level, after Moderna's vaccine did not appear noticeably different than that generated by a high dose of Sanofi's approved Fluzone shot in a separate study, according to data shared by Moderna.
Executives at the biotech defended the results, and asked analysts for patience until the company had more results to share.
"I would really caution against direct comparisons," said Hoge. "We have to provide that data but we think it has to come from the Phase 2 study where we have an active comparator."
In addition to the 50 microgram dose, Moderna will also test a lower 25 microgram dose in that Phase 2 study. Some analysts, though, saw that move as a response to the shot's side effect profile.
In a note to clients, SVB Leerink analyst Mani Foroohar wrote that Moderna's choice to advance a lower dose of its vaccine, along with its plans to test the drug against a standard rather than high dose of Fluzone, represents a "tacit admission by the company of these safety concerns."
Moderna could have competition in developing an mRNA vaccine for seasonal influenza, too. Pfizer, GlaxoSmithKline and Sanofi also hope to develop mRNA shots with their respective partners BioNTech, CureVac and Translate Bio, the latter of which Sanofi acquired earlier this year.
Eventually, Moderna's goal is to prove a single dose booster vaccine that could be given to protect against COVID-19, influenza and respiratory synctial virus, all in one shot.