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

Eli Lilly & Co.’s highly anticipated next-generation weight-loss vaccine did not increase overall heart risk in a new study, the company said, helping to allay ongoing concerns about its potential as it approaches regulatory review.

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

But Lilly will seek approval from U.S. regulators later than investors had hoped. The company said Thursday it plans to apply for U.S. Food and Drug Administration approval early next year. Some Wall Street analysts expected an application to be filed by the end of 2026.

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

The delay is partly due to Lilly planning to submit retatrutide under an approval pathway known as a Biologics License Application, which is often used for products such as vaccines and gene therapies. More complex requirements are required for the BLA, which Lilly says it is working to complete. If the FDA stops approving retatrutide as a biologic drug, the government will have a longer road to go before being subject to price cuts and will have a stronger defense against copycats.

Lilly’s weight-loss vaccine, Zepbound, is the most popular weight-loss drug on the market today, but the company is developing alternatives that offer benefits such as being more effective, easier to take, or with fewer side effects. Retatrutide is a critical part of maintaining its lead over rival Novo Nordisk A/S in a highly competitive market for next-generation weight loss drugs. The experimental vaccine works by combining three different intestinal hormones (GLP-1, GIP and glucagon), providing an advantage over other treatments.

Lilly Science and Product Officer reacted

“If approved, retatrutide would be a first: the first triple agonist, a drug that acts on three pathways simultaneously,” said Lilly Chief Science and Product Officer Daniel Skovronsky. “In practice, this means more room for doctors and patients to find an approach that suits each person.”

Analysts said the latest results reinforce retatrutide’s “best-in-class” potential. But the data raised some curiosity about the drug’s ability to actually reduce heart attacks and strokes; this is a benefit also seen with other weight loss medications. Lilly is conducting a separate trial designed to test whether retatrutide can improve heart outcomes.

“These data read favorably in terms of retatrutide’s effectiveness and overall benefit-risk profile, but the limited cardiovascular event data set may raise some questions,” BMO Capital Markets analyst Evan Seigerman said in a note.

Lilly has been fighting for years to have retatrutide classified as a biologic drug. Potentially billions of dollars are at stake for the company: In studies, retatrutide has been proven to be more powerful than other weight loss drugs on the market; analysts were expecting sales of almost $16 billion by 2036. People are already clamoring to get their hands on black market versions of the vaccine.

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

According to Lilly, this should be enough to classify it as biological. The company even took the fight to federal court, arguing that the FDA interpreted the rule too narrowly: “These differences in regulatory treatment have significant consequences for Lilly at nearly every stage of the development, licensing, and marketing of retatrutide,” the company wrote in a complaint filed in the U.S. District Court for the Southern District of Indiana in 2024.

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