By james art 
Months after securing a label extension to reduce cardiovascular events, Novo Nordisk reported Friday that its semaglutide produced superior improvement over placebo in liver fibrosis in patients with steatohepatitis associated with metabolic dysfunction.
Semaglutide — marketed as Wegovy for weight loss — met the primary endpoints in Part 1 of the pivotal phase III ESSENCE study, demonstrating “statistically significant and superior improvement in liver fibrosis without worsening of steatohepatitis, as well as resolution of steatohepatitis without worsening of liver function.” 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 without worsening of steatohepatitis, while 62.9% of those treated with semaglutide enjoyed resolution of steatohepatitis without worsening liver fibrosis versus 34.1% for the placebo group. The safety profile is consistent with previous trials of semaglutide, Novo said.
Data were taken from the first 800 patients in a double-blind study 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 weeks of data from all 1,200 patients, are expected in 2029, according to a note to investors from Jefferies analysts.
The analysts noted that the benefit was “broadly as expected,” adding that “the placebo effect appears to be relatively high at the MASH split endpoint, which has been observed in more recent studies and in larger programs.”
BMO Capital Markets analyst Evan David Sagerman said in an investor note that the fibrosis benefit was “particularly impressive with this endpoint hotly debated before the report.” Seigerman noted that ESSENCE’s results appear comparable to Eli Lilly’s previous SYNERGY-NASH results.
Analysts at William Blair, meanwhile, said the results were comparable to Madrigal’s recently approved MASH drug Rezdiffra. “We think the rate of improvement in fibrosis is similar to that of Madrigal. . . Rezdiffra,” they wrote in an investor note, adding that the placebo-adjusted improvement in fibrosis without worsening of steatohepatitis was 12% with the 100 mg dose of Rezdiffra compared with 14% for semaglutide in the ESSENCE trial.
Novo plans to present detailed results from ESSENCE at a medical conference later this year. Analysts at William Blair speculated that “given the practice-changing potential of these results,” the data may be presented at the upcoming American Association for the Study of Liver Disease conference, to be held Nov. 15-19 in San Diego.
Martin Holst Lange, Novo’s executive vice president and head of development, said the company was “very pleased” with the trial results. “Among people who are overweight or obese, 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 US and the EU in the first half of 2025. If semaglutide ultimately wins MASH approval, it will follow in March 2024. label extension to reduce the risk of cardiovascular death, heart attack and stroke in adults with cardiovascular disease who are overweight or obese.
Both Novo and rival Eli Lilly are actively looking expansion their respective weight loss drugs in 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 outcome data for GLP-1+ therapeutics,” Sagerman said in his note.