Lilly Withdraws Tirzepatide Application to FDA for Heart Failure

Rather quietly this week, Eli Lilly and Company announced that it had withdrawn an application to FDA for an indication to use tirzepatide (Zepbound) in treating heart failure – specifically for HFpEF. This news came up in a briefing for investors, with Lilly’s Chief Scientific Officer, Dan Skovronsky, saying:

“Following discussions with the FDA, we’ve withdrawn our U.S. application for the heart failure with preserved ejection fraction indication for tirzepatide. We believe the positive phase three data from the SUMMIT trial do support an indication. However, FDA indicated an additional confirmatory clinical trial is required. Regulatory reviews are ongoing in other countries.”

Disappointing,
but Not Unprecedented

Obviously, this is a disappointing turn of events for Lilly. But this is precisely what happened to an HFpEF indication for semaglutide in heart failure. Novo Nordisk withdrew its application for Wegovy in HFpEF last year and resubmitted it to FDA earlier this year. To augment their case for the indication, Novo published a pooled analysis of heart failure outcomes from four prior studies. Semaglutide now appears to be on track for a possible approval later this year.

Skovronsky was rather tentative about the prospects for Zepbound in this indication:

“That [the SUMMIT trial] was a study with a really strong and profound benefit for patients. So we were really excited about the opportunity to help patients with that. From the FDA perspective, they want multiple trials to support this indication.

“It’s possible we could get additional data from other trials to support a resubmission here. On the other hand, just remember that all the patients in this trial and for this indication are already covered under the obesity indication. So it’s not a new population to treat. It’s rather a new benefit for people that might already be understood to doctors today.

“It’s a bit unfortunate we’re in this position. It could have a curtailing effect on investments in HFpEF – which is a pretty serious unmet medical need. So I’m sorry to see that. But it’s kind of hard to think of the incentive for doing large outcome trials in this population that’s already covered under an existing indication if the benefits are well understood.”

So it seems tirzepatide has merit for persons with obesity and heart failure. But the open question is whether regulatory hurdles are too daunting for Lilly to pursue the indication in the U.S.

Click here for more on the unmet medical need in heart failure and here for perspective on the role for tirzepatide.

Heart Labyrinth, illustration by AnonMoos / WikiMedia Commons

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May 3, 2025