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Novo Nordisk said Sunday that an exploratory analysis of its ESSENCE trial found improvements in several liver-related markers among adults with MASH and liver scarring whose body mass index was below 27. The findings add evidence about once-weekly Wegovy 2.4 mg injections in a group that can be overlooked when the liver disease is associated mainly with obesity, but they do not prove fewer serious liver complications.
The company announced the findings November 8 at The Liver Meeting in Denver. Its post hoc analysis covered 106 adults drawn from the first 800 randomized participants in the trial’s 72-week interim analysis. Post hoc means researchers examined the subgroup after the trial was designed; Novo described the results as exploratory and hypothesis-generating.
A closer look at patients with lower BMI
MASH, short for metabolic dysfunction-associated steatohepatitis, is a liver disease that can progress to serious scarring. The subgroup had a BMI below 27 kilograms per square meter, rather than being selected for obesity.
“MASH can affect people of any body type,” said Michelle Skinner Moore, Novo’s vice president for medical affairs. She said the analysis examined a population that had received less attention because of the disease’s association with obesity.
At week 72, comparisons with placebo favored semaglutide 2.4 mg on ALT and AST, enzymes used as markers of liver injury; the FAST disease-activity score; and two fibrosis markers, ELF and PRO-C3. The estimated treatment ratios for ALT and AST were 0.61 and 0.67, respectively, with 95% confidence intervals below 1.0.
The ELF score difference was minus 0.45, while the PRO-C3 treatment ratio was 0.82. These are comparisons between treatment groups, not a declaration that liver damage disappeared in every patient.
Not every measurement gave a clear result
The liver-stiffness measurement known as VCTE-LSM had an estimated treatment ratio of 0.88, but its 95% confidence interval ranged from 0.73 to 1.06. Because that range includes 1.0, the analysis did not establish a clear treatment difference on that measure.
That distinction limits any claim that every marker improved. The findings concern laboratory and non-invasive measurements in a relatively small subgroup, not proof that treatment prevented liver failure, transplant or other clinical events.
“This analysis is not about any single biomarker, but suggests a pattern across measures of liver injury, disease activity and fibrosis,” said Jörn Schattenberg of Saarland University Medical Center in Germany. Novo also posted the presentation’s study page.
The longer trial still has a different question to answer
ESSENCE is an ongoing phase 3 trial of 1,197 adults with MASH and moderate-to-advanced fibrosis. Participants were randomized two to one to semaglutide 2.4 mg or placebo, alongside standard care, for 240 weeks.
The first part examined liver-biopsy outcomes at 72 weeks in the first 800 participants. The ongoing second part is designed to test whether treatment lowers the risk of liver-related clinical events at 240 weeks. Sunday’s subgroup analysis does not answer that longer-term question.
The announcement is a research update, not a new FDA approval or product launch. Novo said semaglutide 2.4 mg already has accelerated U.S. approval for adults with MASH and moderate-to-advanced fibrosis without cirrhosis, with continued approval potentially dependent on confirmation of clinical benefit. The company also noted its boxed warning for possible thyroid tumors, including cancer, and that it should not be used by people with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2.
For Novo, the new analysis broadens the evidence it can discuss around an existing medicine. For patients and clinicians, its narrower message is that body size alone does not settle whether MASH deserves attention, while the durability and clinical meaning of the subgroup findings still require further study.
JBizNews Desk | PLAINSBORO, NEW JERSEY
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