Harrison S, et al. Abstract LB005. Presented at: International Liver Congress; June 22-26, 2022; London (hybrid meeting).
Harrison reports financial support from Akero, Altimmune, AstraZeneca, Axcella, 89 Bio, Boehringer-Ingelheim, Corcept, Chronic Liver Disease Foundation, Cymabay, Echosens, Enyo, Galectin, Galmed, Genentech, Genfit, Gilead, GSK, Hepion, Hightide, HistoIndex, Intercept, Madrigal, Medspace, Metacrine, NGM Bio, NorthSea, Novartis, Novo Nordisk, Nutrasource, Perspectum, Poxel, Sagimet, Sonic Incytes, Terns and Viking.
LONDON — Resmetirom was safe and well tolerated at 100 mg and 80 mg doses in patients with nonalcoholic steatohepatitis, according to late-breaking research presented at the International Liver Congress.
“The primary and key secondary endpoints from the study were achieved,” Stephen Harrison, MD, medical director for Pinnacle Clinical Research in San Antonio and visiting professor of hepatology at Oxford University, told Healio. “Resmetirom was safe and well tolerated and provided significant reductions in liver fat, low-density lipoprotein cholesterol and other atherogenic lipids vs. placebo.”
In the randomized, double-blind, phase 3b MAESTRO-NAFLD-1 trial, Harrison and colleagues investigated the safety and tolerability of resmetirom, a once-a-day oral thyroid hormone receptor beta-selective agonist, vs. placebo. They enrolled 1,143 patients with NASH, who were randomized to receive placebo, 80 mg or 100 mg resmetirom, or 100 mg open label for 52 weeks. Researchers noted that discontinuations (22.5%) did not differ by treatment.
“Patients achieved significant reductions relative to placebo in alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase,” Harrison said. “For those patients with sufficient baseline liver stiffness, as measured by FibroScan vibration-controlled transient elastography or magnetic resonance elastography, responder analyses showed statistically significant responses in the resmetirom groups compared with placebo.”
According to study results, adverse event withdraws occurred in 2.4% of patients in the 80 mg arm, 2.8% in the 100 mg arm and 1.3% in the placebo arm. Treatment-emergent adverse events occurred in 88.4%, 86.1% and 81.8% of patients, respectively. The most common adverse events, reported with greater frequency in the resmetirom groups compared with placebo, were mild diarrhea or increased stool frequency at the beginning of therapy.
“Resmetirom has the potential to be the first medication approved for patients with NASH,” Harrison concluded. “The MAESTRO-NAFLD-1 study provides clinicians with important information about the safety profile of resmetirom and key noninvasive measures of efficacy that may be used in clinical practice to monitor treatment response if resmetirom is approved.
“Patients with NASH are at increased risk for adverse cardiovascular events,” he added, “so the reductions in LDL-C and other atherogenic lipids observed in patients treated with resmetirom are also meaningful.”