MAESTRO-NASH: Resmetirom 80 mg, 100 mg superior to placebo, ‘efficacious’ at 52 weeks
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Key takeaways:
- At week 52, resmetirom outperformed placebo in resolution of metabolic dysfunction-associated steatohepatitis and improvement in fibrosis.
- Incidence of serious adverse events was similar among groups.
Resmetirom 80 mg and 100 mg outperformed placebo in disease resolution and improvement in liver fibrosis among patients with metabolic dysfunction-associated steatohepatitis, according to 52-week results from the MAESTRO-NASH trial.
“Currently, there is no approved pharmacologic treatment for NASH,” Stephen A. Harrison, MD, FAASLD, founder of Pinnacle Clinical Research and Summit Clinical Research and visiting professor of hepatology at the University of Oxford, and colleagues wrote in The New England Journal of Medicine. “Resmetirom is an oral, liver-directed, thyroid hormone receptor beta–selective agonist in clinical development for the treatment of NASH. ... Data from phase 2 and 3 trials have supported the potential efficacy and safety of resmetirom in adults with NASH.”
In the ongoing, phase 3 MAESTRO-NASH trial, 966 patients (mean age, 56.6 years; mean BMI, 35.7) with biopsy-confirmed MASH, previously called NASH, received once-daily resmetirom (80 mg = 322; 100 mg = 323) or placebo (n = 321).
The primary studied endpoints at week 52 included MASH resolution, defined as a reduction of nonalcoholic fatty liver disease activity score by 2 points or more, with no worsening of fibrosis; and improvement in fibrosis by at least 1 stage with no worsening of NAFLD activity score. The key secondary endpoint was percent change from baseline in LDL cholesterol at week 24.
Results showed 25.9% of patients in the resmetirom 80 mg group and 29.9% of patients in the 100 mg group achieved MASH resolution with no worsening of fibrosis compared with 9.7% of those in the placebo group. A reduction in fibrosis of at least 1 stage with no worsening of NALFD score was reported among 24.2% and 25.9% vs. 14.2%, respectively.
Patients in both resmetirom groups experienced a greater reduction from baseline in LDL cholesterol (–13.6% and –16.3%) compared with placebo (0.1%) at week 24. Further, triglyceride, non-HDL cholesterol, apolipoprotein B, apolipoprotein C-III and lipoprotein(a) levels “appeared to decrease more from baseline” at weeks 24 and 52 among those who received resmetirom.
Serious adverse events were reported in 10.9% and 12.7% of patients in the resmetirom 80 mg and 100 groups, respectively, and 11.5% in the placebo group.
“Data for the first 1,050 patients from the MAESTRO-NASH trial, together with data from completed resmetirom trials, support the potential for resmetirom to provide benefit to patients with NASH and liver fibrosis,” Harrison and colleagues wrote. “Both the 80 mg dose and the 100 mg dose of resmetirom were shown to be efficacious with respect to the two primary histologic endpoints in patients with NASH and liver fibrosis.”
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