Eli Lilly Slides as FDA Case Sparks GLP-1 Safety Talk

Key Moments

Market Reaction to FDA Adverse Event Data

Investing.com – Shares of Eli Lilly and Company (NYSE:LLY) fell 3% on Monday, while Novo Nordisk (NYSE:NVO) advanced 2%, after Evercore ISI analyst Umer Raffat drew attention to a liver-related case in the U.S. Food and Drug Administration’s adverse event database that he said has “potential to create confusion” for Eli Lilly.

Raffat identified an instance of hepatic failure in the FDA Adverse Event Reporting System connected with Foundayo, Eli Lilly’s oral GLP-1 therapy. The case involved a 56-year-old man and may have taken place on or before April 15, with the formal report submitted to the FDA on April 30.

How the Foundayo Case Compares With Other GLP-1 Drugs

To frame the new report, Raffat highlighted that hepatic failure has also appeared in association with other GLP-1 medicines. According to the analyst, Mounjaro has been linked to 30 hepatic failure cases and Zepbound to 2 cases, while Ozempic has 33 such reports and Wegovy 15 in the adverse event system.

Raffat further contrasted broader serious hepatic events for these therapies with their prescription volumes since the third quarter of 2018. Combined, Mounjaro and Zepbound showed 311 serious hepatic cases against approximately 105 million prescriptions, whereas Ozempic and Wegovy together had 447 serious hepatic cases versus approximately 150 million prescriptions over the same period.

Commenting on the context of the single Foundayo report, Raffat wrote that “we cannot look at this single liver case in a silo … and such cases do tend to occur on other GLPs as well because of various confounding factors.”

Trial Data and Safety Profile for Foundayo

Raffat pointed out that Foundayo’s hepatic safety profile has been evaluated across several clinical studies. This includes the ACHIEVE-4 trial, which enrolled 2,800 patients and was specifically designed at the FDA’s request to assess liver-related safety. According to the analyst, this large study did not detect a hepatic safety signal.

Even so, Raffat argued that “onus is on LLY to ensure that proper and expedient adjudication of each of such liver cases is being done commercially to avoid any confusion.” He linked this caution to prior concerns around liver toxicity for other oral GLP-1 candidates from Pfizer, as well as elevations in ALT levels seen in earlier Foundayo studies.

Analyst Responses to the Market Selloff

Other analysts weighed in on the situation and the share price reaction. Wolfe analyst Alexandria Hammond said Eli Lilly had dismissed the reported hepatic failure after concluding it was not caused by Foundayo. “With the additional context from LLY, we feel confident that today’s pre-market trading reaction is overdone (LLY -3%), and we’d be buyers on weakness,” Hammond wrote.

Bernstein’s Christian Moore also expressed confidence in the existing body of clinical evidence. He argued that a liver toxicity issue is unlikely to have been overlooked in trials, given the extent of data generated on the drug. “We’re buyers today of this LLY -3% early reaction to sell-side highlighting a report of hepatic failure on April 30 for a 56-year old male who took Foundayo (oral GLP-1),” Moore stated.