Novo Nordisk's semaglutide, marketed as Wegovy for weight loss, has shown promising results in the Phase III ESSENCE trial for patients with metabolic dysfunction-associated steatohepatitis (MASH). The trial demonstrated a statistically significant and superior improvement in liver fibrosis and resolution of steatohepatitis compared to placebo, potentially offering a new treatment option for this prevalent condition.
Key Findings from the ESSENCE Trial
After 72 weeks, 37% of participants treated with semaglutide 2.4 mg experienced an improvement in liver fibrosis with no worsening of steatohepatitis, compared to 22.5% in the placebo group. Furthermore, 62.9% of those treated with semaglutide achieved resolution of steatohepatitis with no worsening of liver fibrosis, versus 34.1% for the placebo group. These data are from the first 800 patients in the double-blinded trial of 1,200 adults with MASH and moderate to advanced liver fibrosis. The safety profile was consistent with previous semaglutide trials.
Analyst Perspectives
Analysts from Jefferies noted that the benefits were "broadly as expected," while also pointing out the relatively high placebo effect observed in the MASH resolution endpoint. BMO Capital Markets analyst Evan David Seigerman highlighted the "particularly impressive" benefit on fibrosis. William Blair analysts indicated that the results compared favorably to Madrigal's recently approved MASH drug, Rezdiffra, noting 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.
Implications for MASH Treatment
Martin Holst Lange, executive vice president and head of development at Novo Nordisk, emphasized the significant unmet need in MASH, stating that "Among people with overweight or obesity, one in three live with MASH. This has a serious impact on their health." The company plans to present detailed results from ESSENCE at a medical conference later this year and intends to file for regulatory approval in both the U.S. and EU in the first half of 2025.
Future Directions
Results from part 2 of the trial, which will include 240-week data from all 1,200 patients, are expected in 2029. Both Novo Nordisk and Eli Lilly are actively exploring the expansion of their GLP-1 drugs into new indications, including cardiovascular disease and MASH, as well as sleep apnea and kidney disease. This reflects a growing recognition of the potential for these therapeutics to address multiple health challenges beyond weight loss.
