GLP-1s, a class of drugs including Ozempic and Wegovy that have become widely popular for treating obesity and diabetes, are also being studied for NASH, a form of fatty liver disease. But a new small study suggests GLP-1s may not dominate the disease area as they have others.
Akero Therapeutics tested its experimental medicine efruxifermin in conjunction with a GLP-1, and found that patients taking the combination had reduced liver fat and improved markers of liver scarring compared with those taking just a GLP-1, the company said Monday.
“There has been speculation that maybe GLP-1 is so effective in diabetes and obesity that it’s really going to be the key for NASH treatment as well,” said Jonathan Young, co-founder and chief operating officer at Akero. But, the company’s results show that “GLP-1 alone may not be adequate for the complex pathogenesis of NASH.”
NASH, short for nonalcoholic steatohepatitis, affects about 17 million Americans. There are no approved treatments yet for the disease, which has grown into one of the leading causes of liver transplantation and liver cancer.
Akero’s 12-week study included 31 patients who have NASH and type 2 diabetes and were already taking a GLP-1 drug, such as Ozempic or Trulicity.
Among patients taking the combination treatment, 88% achieved normalized liver fat of 5% or less, compared with 10% of people taking just a GLP-1. Additionally, patients on the combination experienced an average 65% reduction in liver fat, versus 10% for those taking solely a GLP-1.
Due to the short length of the study, the researchers didn’t conduct biopsies to look at changes in living scarring, called fibrosis, which is a key endpoint that regulators evaluate with NASH treatments. But the researchers looked at biomarkers of fibrosis — such as PRO-C3, the ELF score, and FAST score — and patients on the combination showed greater improvements.
An earlier Phase 2 trial that did conduct biopsies showed that Akero’s drug on its own improved fibrosis at twice the rate of a placebo without worsening other symptoms.
Both Akero’s drug and GLP-1 treatments have gastrointestinal side effects like nausea and diarrhea, so there was concern that using them in combination would be intolerable for patients, said Tim Rolph, co-founder and chief scientific officer. But the study found that the combination was generally well-tolerated, with one participant discontinuing due to nausea.
The company plans to start a Phase 3 trial of its NASH drug in the second half of this year, and results from this study can help in supporting the enrollment of patients already on a GLP-1 into the Phase 3 trial, Rolph said.
Other companies are pushing ahead with studying GLP-1s on their own in NASH. Novo Nordisk is conducting a Phase 3 trial with semaglutide, the underlying ingredient in Ozempic and Wegovy, even though a Phase 2 trial had shown that the drug didn’t significantly improve fibrosis. Eli Lilly is also testing tirzepatide, the underlying ingredient in Mounjaro, for NASH.
“We can assume that GLP-1 will be very widely used in this population, even without having a formal NASH label,” Akero’s Rolph said. “So being compatible, if you will, and bringing additional value specific to NASH on top of these therapies, I think, is a profile that will enable us to be successful.”
Akero is also up against several non-GLP-1 competitors. Intercept Pharmaceuticals’s drug is pending a decision from the Food and Drug Administration, but advisers to the agency last month voted against approving it. Meanwhile, Madrigal Pharmaceuticals plans to submit a rival drug for FDA review before the end of this month.
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