Lilly touts fibrosis win as it pads case for tirzepatide in MASH

Back in February, Eli Lilly teased “clinically meaningful” results around the ability of its dual GLP-1/GIP med tirzepatide to curb fibrosis in patients with fatty liver disease. Now, the company is laying out the fine details.

In Lilly’s phase 2 SYNERGY-NASH trial, 54.9% of patients on tirzepatide 5 mg, 51.3% of patients on tirzepatide 10 mg and 51% of patients on tirzepatide 15 mg saw their fibrosis decrease by at least one stage without their metabolic dysfunction-associated steatohepatitis (MASH) worsening.

That compared with just 29.7% of MASH patients in the placebo group who saw their fibrosis improve, according to a late-breaking abstract published ahead of the EASL International Liver Congress.

Analysts at Evercore ISI called tirzepatide’s fibrosis results “solid” and said they “may be slightly better” than those for Madigral Pharmaceuticals' approved MASH drug Rezdiffra. Still, the analysts cautioned that the Lilly readout is “not quite as strong” as data from clinical-stage MASH competitors Akero Therapeutics and 89bio.

In March, Madrigal ended a decades-long wait for an effective MASH treatment when its candidate resmetirom was approved as the first drug for the fatty liver disease under the brand name Rezdiffra. Following Lilly’s tirzepatide data drop, Madrigal’s stock plunged nearly 9% in early Wednesday trading, Investor’s Business Daily reported.

Still, Madrigal and other MASH players shouldn’t be too intimidated, with the Evercore team positing that the disease “is not a ‘one-drug-suits-all’ marketplace.”

“With large markets of this magnitude, we think there is room for different treatment options for patients with different needs including daily oral pills and injectable products,” the analysts explained in a Wednesday note to clients. All told, the Evercore team figures Rezdiffra still has a shot at a roughly $4 billion market opportunity in the U.S.

Lilly’s fibrosis data come after the company unveiled positive midstage results in MASH in early February. At the time, Lilly said tirzepatide helped 74% of overweight or obese adults with MASH clear the disease with no worsening of liver scarring after 52 weeks. The 74% figure came from tirzepatide’s 15-mg dose. For the 10-mg and 5-mg doses, clearance rates clocked in at 63.1% and 51.8%, respectively.

In the placebo group, just 12.6% of patients experienced MASH clearance.

Despite the apparent MASH win, it remains unclear what Lilly’s plans are for a potential tirzepatide label expansion, the Evercore ISI team pointed out.

Tirzepatide is currently approved in Type 2 diabetes and obesity as Mounjaro and Zepbound, respectively. Meanwhile, Lilly is testing its drug in a suite of other indications, too, such as sleep apnea in obese patients and heart failure with preserved ejection fraction.

Demand remains an ongoing concern for the compound, so much so that Lilly is slotting $9 billion to establish a record-breaking production facility in Indiana.

As for Madigral, the company early last month said it had enough cash on hand to “fully resource” the launch of Rezdiffra, with CEO Bill Sibold citing “remarkable interest” for the med among doctors.

At the time, Madrigal noted it had reached more than 80% of its top physician targets, which primarily include about 6,000 high-volume MASH-treating physicians. All told, Madrigal is targeting 315,000 MASH patients actively being treated by doctors in the U.S.

Elsewhere, Viking Therapeutics this week unveiled secondary endpoints results on its own MASH hopeful after previously reporting that its phase 2b study VOYAGE had met its primary endpoint.

Specifically, up to 75% of patients who received Viking’s investigational drug, known as VK2809, achieved MASH resolution with no worsening of fibrosis versus 29% of patients in the trial’s control arm. Up to 57% of patients experienced a one-stage or greater improvement in fibrosis with no worsening of MASH compared with 34% for placebo.