Eli Lilly’s next-generation weight-loss shot clears another hurdle

Eli Lilly & Co.’s highly anticipated next-generation weight-loss shot didn’t increase overall heart risk in a new study, the company said, helping dispel lingering concerns over its potential as it nears regulatory review.

Lilly’s trial evaluated retatrutide’s cardiovascular safety in people with obesity and heart disease after earlier studies raised questions about a possible increase in heart rhythm abnormalities. The latest findings — plus another new study in patients with obesity and diabetes — help solidify the drug’s blockbuster potential.

However, Lilly will seek approval from US regulators later than investors hoped. The company said Thursday that it plans to file for US Food and Drug Administration approval early next year. Some Wall Street analysts expected a filing by the end of 2026.

Lilly’s shares were down less than 1% before markets opened in New York.

The delay stems, in part, from the fact that Lilly is planning to submit retatrutide under an approval pathway known as a Biologics License Application, which is typically used for products like vaccines and gene therapies. There are more complex requirements needed for a BLA, which Lilly said it’s working to complete. If the FDA ends up approving retatrutide as a biologic medicine, it would have a longer runway before being subject to government price cuts and a stronger defense against would-be copycats.

Lilly’s weight-loss shot Zepbound is the most popular weight-loss medication on the market today, but the company is developing alternatives that are more effective, easier to take or offer benefits like fewer side effects. Retatrutide is a critical part of maintaining its lead over rival Novo Nordisk A/S in the highly competitive market for next-generation weight-loss drugs. The experimental shot works by combining three different gut hormones — GLP-1, GIP and glucagon — giving it an edge over other treatments.

The latest results cement retatrutide’s “best-in-class” potential, analysts said. However, the data left some wondering about the drug’s ability to actually reduce heart attacks and strokes — a benefit seen with other weight-loss medications. Lilly is running a separate trial designed to test whether retatrutide can improve heart outcomes.

“These data read positively for retatrutide’s efficacy and overall benefit-risk profile, although the limited cardiovascular event dataset could raise some questions” ahead of the heart outcomes study, BMO Capital Markets analyst Evan Seigerman said in a note.

Lilly has been fighting for years to get retatrutide classified as a biologic drug. There’s potentially billions of dollars at stake for the company: In studies, retatrutide has proven to be more powerful than any other weight-loss drug on the market, with analysts expecting almost $16 billion in sales by 2036. Already, people have been clamoring to get their hands on black-market versions of the shot.

The fight over whether retatrutide is a biologic or a conventional drug comes down to amino acids, which are the building blocks of proteins. Federal law says that biologics must contain more than 40 amino acids. Retatrutide sits right on that boundary with a backbone of 39 amino acids, plus a side chain.

According to Lilly, that should be enough to classify as a biologic. The company has even taken the fight to federal court, arguing that the FDA is interpreting the rule too narrowly: “These differences in regulatory treatment have substantial ramifications for Lilly at nearly every stage of retatrutide’s development, licensure, and marketing,” the company wrote in a 2024 complaint filed in the US District Court for the Southern District of Indiana.

Last year a federal judge handed Lilly a partial win, ordering the FDA to reconsider its classification.