Lilly Highlights Tirzepatide Success in MASH Fibrosis

As newer treatment options for metabolic dysfunction-associated steatohepatitis (MASH) emerge, experts from Evercore ISI suggest that the condition will not be dominated by a singular medication. In February, Eli Lilly disclosed promising results about its dual GLP-1/GIP drug, tirzepatide, for reducing fibrosis in patients with fatty liver disease. The company has now provided detailed data from its phase 2 SYNERGY-NASH trial. The findings indicate that 54.9% of patients on a 5 mg dose, 51.3% on a 10 mg dose, and 51% on a 15 mg dose of tirzepatide exhibited a reduction in fibrosis by at least one stage, without worsening their MASH condition. In contrast, only 29.7% of patients in the placebo group experienced similar improvements.

Analysts at Evercore ISI praised tirzepatide’s impact on fibrosis, noting it may be slightly superior to Madrigal Pharmaceuticals' Rezdiffra, the only approved MASH medication. However, they cautioned that Lilly’s data is not as robust as those from competitors Akero Therapeutics and 89bio, which are still in clinical stages.

In March, Madrigal Pharmaceuticals achieved a significant milestone with the approval of resmetirom, marketed as Rezdiffra, marking the first effective MASH treatment. Following Lilly’s tirzepatide data release, Madrigal’s stock saw a nearly 9% dip. Despite this, Evercore ISI emphasizes that the MASH treatment landscape is diverse, requiring a range of therapeutic options to cater to different patient needs, including both oral and injectable solutions. Even with new competitors, Rezdiffra is still projected to capture a $4 billion market in the U.S.

Lilly’s latest fibrosis data follows its February announcement of positive midstage MASH results. According to the company, 74% of overweight or obese adults on a 15-mg dose of tirzepatide saw MASH clearance without worsening of liver scarring over 52 weeks. For lower doses of 10 mg and 5 mg, the clearance rates were 63.1% and 51.8%, respectively. Only 12.6% of patients in the placebo group achieved MASH clearance.

Despite these promising results, it remains uncertain whether Lilly will pursue a label expansion for tirzepatide. Currently, tirzepatide is approved for Type 2 diabetes and obesity under the brand names Mounjaro and Zepbound. Additionally, Lilly is investigating its efficacy in other conditions, including sleep apnea in obese patients and heart failure with preserved ejection fraction. Concerns about meeting demand persist, prompting Lilly to invest $9 billion in a new production facility in Indiana.

Madrigal, on the other hand, has reported sufficient funds to support the launch of Rezdiffra, with CEO Bill Sibold highlighting strong interest from healthcare providers. The company has reached over 80% of its target physicians, focusing on around 6,000 high-volume MASH-treating doctors. In total, Madrigal is aiming to treat approximately 315,000 MASH patients in the U.S.

Meanwhile, Viking Therapeutics recently shared secondary endpoint results from its VOYAGE phase 2b study for its MASH candidate, VK2809. The data revealed that up to 75% of patients on VK2809 achieved MASH resolution without worsening fibrosis, compared to 29% in the control group. Additionally, 57% saw a one-stage or greater improvement in fibrosis without worsening MASH, versus 34% in the placebo group.

In summary, the race to treat MASH is intensifying, with multiple contenders showing promising results. Both established and emerging treatments are vying for a share of the market, suggesting a future where a variety of therapeutic options will be available to meet diverse patient needs.