In part 1 of the pivotal ESSENCE trial, Novo Nordisk’s weight loss drug Wegovy demonstrated “statistically significant and superior improvement” in liver fibrosis in patients with metabolic dysfunction–associated steatohepatitis.
Months after securing a label expansion for reducing cardiovascular events, Novo Nordisk reported Friday that its semaglutide elicited superior improvement over placebo in liver fibrosis in patients with metabolic dysfunction–associated steatohepatitis.
Semaglutide—marketed as Wegovy for weight loss—hit the primary endpoints in part 1 of the pivotal Phase III ESSENCE trial, demonstrating a “statistically significant and superior improvement in liver fibrosis with no worsening of steatohepatitis as well as resolution of steatohepatitis with no worsening of liver fibrosis” compared to placebo, the company announced in a press release.
After 72 weeks, 37% of trial participants treated with semaglutide 2.4 mg and 22.5% of their placebo counterparts saw improvement in liver fibrosis with no worsening of steatohepatitis, while 62.9% of those treated with semaglutide enjoyed resolution of steatohepatitis with no worsening of liver fibrosis versus 34.1% for the placebo group. The safety profile was in line with previous semaglutide trials, Novo reported.
The data were taken from the first 800 patients in the double-blinded trial of 1,200 adults with metabolic dysfunction–associated steatohepatitis (MASH) and moderate to advanced liver fibrosis. Results from part 2 of the trial, which will include 240-week data from all 1,200 patients, are expected in 2029, according to an investor note from Jefferies analysts.
The analysts noted that the benefit was “broadly as expected,” while adding that “the placebo effect seems relatively high in the MASH resolution endpoint, which has tended to have been the case in more recent studies and in larger programmes.”
BMO Capital Markets analyst Evan David Seigerman said in an investor note that the benefit on fibrosis was “particularly impressive with that endpoint hotly debated ahead of the readout.” Seigerman observed that results of ESSENCE appeared comparable to Eli Lilly’s previous SYNERGY-NASH results.
Meanwhile, William Blair analysts said the results compared favorably to Madrigal’s recently approved MASH drug Rezdiffra. “We view the magnitude of the fibrosis improvement as similar to Madrigal’s . . . Rezdiffra,” they wrote in an investor note, adding that the placebo-adjusted improvement in fibrosis with no worsening of steatohepatitis was 12% with the 100 mg dose of Rezdiffra compared to 14% for semaglutide in the ESSENCE trial.
Novo plans to present detailed results from ESSENCE at a medical conference later this year. The William Blair analysts speculated that “given the practice-changing potential of these results,” the data could be presented at the upcoming American Association for the Study of Liver Disease conference, taking place Nov. 15-19 in San Diego.
Martin Holst Lange, executive vice president and head of development at Novo, said the company is “very pleased” with the trial results. “Among people with overweight or obesity, one in three live with MASH. This has a serious impact on their health and represents a significant unmet need,” Lange said in a statement.
Novo plans to file for regulatory approval in both the U.S. and EU in the first half of 2025. If semaglutide ultimately wins approval in MASH, it would follow its March 2024 label expansion to reduce the risk of cardiovascular death, heart attack and stroke in adults with cardiovascular disease who are obese or overweight.
Both Novo and rival Eli Lilly are actively looking to expand their respective weight loss drugs into new indications, including cardiovascular disease and MASH, along with sleep apnea and kidney disease.
“Today’s results continue to support a growing body of secondary outcomes data for GLP-1+ therapeutics,” Seigerman said in his note.
