High dose of resmetirom rapidly reduces hepatic fat, fibrosis, biomarkers in NASH
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Resmetirom rapidly reduced hepatic fat, fibrosis and biomarkers among patients with nonalcoholic steatohepatitis, according to a presentation at the International Liver Congress.
“Consistent with data that has been generated already, we see with a higher dose of 100 mg in open label cohort a drug that is safe, appears to well tolerated with some drops in noninvasive tests that are consistent with overall improvement in liver cell and liver health,” Stephen Harrison, MD, medical director, Pinnacle Clinical Research, University of, Texas, visiting professor of hepatology at the University of Oxford, said during his presentation.
Harrison and colleagues performed an exploratory evaluation of imaging and biomarkers of 169 patients with NASH enrolled in the MAESTRO-NAFLD-1, phase 3 open label study specifically assessing the use of resmetirom (Madrigal) 100 mg daily. Patients were studied for 52 weeks.
Safety, relative percent reduction of MRI-estimated proton density fat fraction at week 16, low-density lipoprotein cholesterol (LDL-C) at week 24, apolipoprotein B and triglycerides, PRO-C3 at week 52, and safety served as the primary secondary endpoints.
Results showed the 169 patients completed 16 weeks and 64 completed 52 weeks. Investigators noted Fibroscan (Echosens; kPa 7.7), and mean MRI-PDFF 18% (7%) were concordant with stage F2 NASH. At 52 weeks, Harrison and colleagues observed MRI-PDFF reduction of 53%, fat fraction overall, and 62% reduction in a sex hormone-binding globulin responder group (all P < .0001). At 16 weeks and 53 weeks, magnetic resonance elastography was statistically significantly reduced.
According to researchers, in comparison to baseline, at 52 weeks the Fibroscan CAP and kpa were reduced. In addition, LDL-C (–23%), apolipoprotein-B (–22%), triglycerides (med, –32 mg/dL), and lipoprotein(a) (–39%) were reduced compared with baseline (P < .0001).
Harrison noted alanine aminotransferase (–22 IU), aspartate aminotransferase (–12 IU) and gamma-glutamyl transferase (–25 IU) decreased from baseline (all P < .0001). They observed significant reductions in inflammatory and fibrosis biomarkers high-sensitivity C-reactive protein, reverse T3, enhanced liver fibrosis and M30. No safety flags were noted.
“What we found is that the 100 mg dose is very well tolerated,” he said. “There are some early, mild [gastrointestinal] issues with loose stools that tend to abate after about 2 weeks and that was seen in roughly 10% over the placebo.”
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Harrison, et al. Abstract: GS-2563. Presented at: The International Liver Congress; June 23-26 (virtual meeting).
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