Moderna spent much of its fourth-quarter earnings call reassuring investors that its flu vaccine is still on an approval pathway after lukewarm phase 3 data dinged the company’s hot streak.
It was an unfamiliar position for the famed biotech's top brass Thursday, after the COVID-19 vaccine success and a recent phase 3 RSV readout built monumental expectations that the company’s mRNA platform would continue to churn out clinical home runs. But company executives, namely President Stephen Hoge, M.D., are still bullish that looming efficacy data will validate regulatory approval.
“I would note that it is well-precedented—in fact, many of the currently approved influenza vaccines have, in the past missed on noninferiority for an influenza B strain endpoint here or there and still have received full approval or accelerated approvals,” said Hoge.
The comments come after phase 3 immunogenicity data from the Southern Hemisphere portion of Moderna’s trial showed that the first-generation flu vaccine mRNA-1010 was not better than approved shots against the influenza B strains. The vaccine was more successful against the influenza A strains, which currently make up nearly all flu cases in the U.S this season.
Moderna's shares were down more than 7% Thursday morning, from $158.17 to $146.89. The company's share price has fallen roughly $20 per share since the news of the mixed data from the flu shot trial was announced.
The company previously said that prior discussions with regulators suggested that an accelerated approval could be granted based on the immunogenicity study. But with the data out, Moderna appears to be hedging its bets, not committing to any single regulatory route until more efficacy data is available. The timing of that data is also in limbo.
Hoge says a first interim analysis will be reviewed in the first quarter of 2023, with some 200 flu cases accrued so far, almost all of which are influenza A strains. But a second interim analysis may be required to demonstrate noninferiority or superiority if that’s not evident in the first look.
“If we do not yet meet that threshold, then we'll be looking forward to subsequent interim analyses in that study,” said Hoge.
The implications and significance of these readouts have broader pipeline implications given Moderna’s combo vaccine aspirations. The company has explained in the past that regulators will need to sign off on each shot individually before they would green light a combo option. Moderna currently has three combo shots in clinical development that include the flu vaccine.
Lucky for Moderna, the flu shot is not the only big prospect in its pipeline, with an FDA breakthrough designation just secured for its personalized cancer therapy, mRNA-4157, being developed with Merck & Co. Moderna says that Merck is working to rapidly enroll a phase 3 trial of the shot, with a potential accelerated approval not off the table. The treatment is currently being tacked onto Keytruda in patients with high-risk melanoma but Moderna says it’s looking to swiftly expand clinical development to additional indications where Keytruda is already approved and beyond.
The expedited enrollment plans are evidence that FDA Commissioner Robert Califf’s calls for companies to begin enrollment of confirmatory trials prior to applying for accelerated approval are being heard. Hoge wouldn’t elaborate on what the timeline was for enrolling the phase 3 trial, saying only that the companies were working “as fast as possible.”