Mazen Nouredden, MD, MHSc1, Jörn M. Schattenberg, MD2, Rebecca Taub, MD3, Dominic Labriola, PhD3, Rohit Loomba, MD, MHSc4 1Houston Methodist Hospital, Houston, TX; 2Saarland University Medical Center, Homburg, Saarland, Germany; 3Madrigal Pharmaceuticals, West Conshohocken, PA; 4University of California San Diego School of Medicine, La Jolla, CA
Introduction: MAESTRO-NASH (NCT03900429) is an ongoing 54-month, randomized, double-blind, placebo-controlled Phase 3 trial evaluating the efficacy of resmetirom in patients with biopsy-confirmed nonalcoholic steatohepatitis (NASH) and fibrosis. 966 patients with biopsy-confirmed NASH were randomized 1:1:1 to resmetirom 80 mg, resmetirom 100 mg, or placebo administered once daily. Histologic endpoints were assessed after 52 weeks. Dual primary endpoints at Week 52 were achieved with both resmetirom 80 mg and 100 mg: NASH resolution with no worsening of fibrosis (NR) or ≥1-stage reduction in fibrosis with no worsening of NAS (FI).
Body weight is the major factor influencing exposure to resmetirom in patients with NASH/MASH. This post-hoc analysis was performed to provide additional evidence of a relationship between resmetirom dose, baseline body weight and body mass index (BMI).
Methods: To assess the impact of baseline body weight and BMI on resmetirom response, we stratified resmetirom efficacy data on the dual endpoints based on baseline patient body weight (≤100 and >100 kg) and BMI (≥35 and < 35 kg/m2).
Results: For patients treated with resmetirom 80 mg who weighed ≤100 kg, the 30% PDFF response was 66.9%; and in patients with a Week 52 biopsy, 35.4% showed fibrosis improvement (FI) compared with 32% who showed no worsening of fibrosis (NR). In patients >100 kg, the 30% PDFF response was 56.7%; FI=22.5%; and NR=27%. For patients who received resmetirom 100 mg who were ≤100 kg, the 30% PDFF response was 71.7%; FI was 33.6% and NR was 35.8%; for patients >100 kg, PDFF=72.5%; FI=32.5%; NR=35.8%.
Increases in FI were noted relative to placebo for patients who received resmetirom 80 mg (mITT population) who had BMI < 35: 13.0% (5.2, 20.8); NR=33.4% (14.2, 30.6); and in patients with BMI ≥35: FI=7.0% (-0.7, 14.7); NR=9.8% (3.1, 16.6).
Increases were also noted relative to placebo for patients who received 100 mg of resmetirom (mITT population) who had a BMI < 35: FI=11.8% (4.2, 19.4) NR=21.0% (13.4, 28.7); for patients with BMI ≥35: FI=11.1% (3.4, 18.9); NR=20.0% (12.3, 27.7).
Discussion: As shown in these stratified data, resmetirom 100 mg was consistently more effective than 80 mg in achievement of the dual primary endpoints in the sample of patients who had higher baseline body weight and BMI. In patients with a lower BMI, there was no observed difference in efficacy between the 80 and 100 mg resmetirom doses.
Disclosures:
Mazen Nouredden: Altimmune – Advisor or Review Panel Member. Chronwell – Stock Options. Cytodyne – Stock Options. Madrigal Pharmaceuticals – Advisor or Review Panel Member, Consultant. Merck – Advisor or Review Panel Member. Novo Nordisk – Advisor or Review Panel Member. Rivus – Stock Options. Takeda – Advisor or Review Panel Member. Terns – Advisor or Review Panel Member.
Mazen Nouredden, MD, MHSc1, Jörn M. Schattenberg, MD2, Rebecca Taub, MD3, Dominic Labriola, PhD3, Rohit Loomba, MD, MHSc4, 58, Assessment of Resmetirom Efficacy (80 mg vs 100 mg) Stratified by Baseline Body Mass Index and Weight in Patients From the MAESTRO-NASH Trial, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.
