Both Eli Lilly and the partnered companies Boehringer Ingelheim and Zealand Pharma have mid-stage data readouts this week, fueling the race in metabolic dysfunction-associated steatohepatitis.
You would be forgiven if, with all the cancer news from ASCO24 in Chicago this week, you missed the hepatology data dump at the 2024 Congress of the European Association for the Study of the Liver in Milan, Italy. However, there’s a battle brewing between Eli Lilly and the partnered companies Boehringer Ingelheim and Zealand Pharma in metabolic dysfunction-associated steatohepatitis (MASH), previously referred to as nonalcoholic steatohepatitis (NASH).
The drugs being tested in MASH belong to the now-blockbuster class of therapies known as glucagon-like peptide-1 receptor agonists (GLP-1s). Lilly’s tirzepatide is already approved for type 2 diabetes (marketed as Mounjaro) and weight loss (marketed as Zepbound), spaces it shares with Novo Nordisk’s semaglutide products Ozempic and Wegovy—a duopoly that has led to skyrocketing revenue for both companies, which continue to seek additional indications. Meanwhile, Boehringer and Zealand are looking to leap into the space with a GLP-1 agonist, survodutide, which is under investigation for obesity and other indications.
What is interesting this week at the European Association for the Study of the Liver (EASL24) is the GLP-1 clash between Lilly and Boehringer/Zealand in the MASH space, with both sides providing readouts on their latest Phase II data.
MASH is a potentially deadly fatty liver disease that affects more than 115 million people globally and is expected to increase to 357 million by 2030. In March, the FDA approved Madrigal Pharmaceuticals’ Rezdiffra, a liver-directed thyroid hormone receptor (THR)-β agonist, as the first-ever treatment for the disease.
Following a data leak snafu at EASL24 on Thursday, Boehringer and Zealand announced Friday that survodutide demonstrated “breakthrough improvement” in liver fibrosis with no worsening of MASH in 64.5% of patients with F2 and F3 fibrosis. The companies said the new data also revealed up to 52.3% of adults with fibrosis stages F1, F2 and F3 had improvement in fibrosis without worsening of MASH. Survodutide, which is licensed to Boehringer from Zealand, is moving into Phase III trials.
Lilly’s Phase II data will be presented at EASL24 on Saturday as a late breaker, which according to the abstract will show that 54.9% of MASH patients treated with a 5-mg dose of tirzepatide saw at least a one-stage improvement in fibrosis. In the study of MASH patients with F2 and F3 fibrosis, tirzepatide treatment was found to be more effective than placebo in achieving MASH resolution without worsening of fibrosis.
While GLP-1 drugs may have beneficial effects on MASH by improving insulin sensitivity, reducing liver fat accumulation and reversing fibrosis, Jefferies analysts said in a note to investors this week that they “don’t think GLP-1s will eliminate the market opportunity” for Madrigal in MASH. Likewise, Evercore ISI analysts opined, “there is room for different treatment options for patients with different needs, including daily oral pills and injectable products.” Evercore estimated a potential U.S. market opportunity for Madrigal’s Rezdiffra of $4 billion, while Jefferies’ estimate was considerably lower, pegging peak U.S. sales for Rezdiffra at $2.3 billion.
Of course, there are a host of other promising MASH candidates, including Akero Therapeutics. Also at EASL24 this week, Viking Therapeutics announced its candidate VK2809—a thyroid hormone beta receptor agonist—significantly improved secondary histologic endpoints at 52 weeks with no worsening of fibrosis, as assessed by hepatic biopsy. And tomorrow, 89bio will be presenting Phase IIb data for pegozafermin, a specifically engineered glycoPEGylated analog of fibroblast growth factor 21. Meanwhile, new data from Altimmune and a preclinical poster presentation from Aligos Therapeutics also hint at promise in the treatment of MASH.
Still, MASH is a complex and confounding disease that has caused many once-promising programs to be discontinued. However, with a projected $25.7 billion total market by 2032 in the U.S., France, Germany, Italy, Spain, the U.K. and Japan, competitors will continue to be in hot pursuit of Madrigal, which has set the standard. Let the clash of the MASH titans begin!
Greg Slabodkin is the news editor at BioSpace. You can reach him at greg.slabodkin@biospace.com. Follow him on LinkedIn.
