Abstract
Background: Nonalcoholic steatohepatitis (NASH) is a progressive liver disease with no approved treatment. Resmetirom is an oral, liver-directed thyroid hormone receptor-β selective agonist in development for the treatment of NASH with liver fibrosis.
Methods: MAESTRO-NASH is an ongoing Phase 3 trial in adults with biopsy-confirmed NASH and fibrosis stage 1B, 2, or 3. Patients were randomized 1:1:1 to once-daily resmetirom 80 mg, resmetirom 100 mg, or placebo. Dual primary endpoints at Week 52 were NASH resolution with ≥2-point reduction in the nonalcoholic fatty liver disease [NAFLD] activity score [NAS] and no worsening of fibrosis and ≥1-stage improvement in fibrosis with no worsening of NAS.
Results: Overall, 966 patients formed the primary analysis population (resmetirom 80 mg [n=322], resmetirom 100 mg [n=323], or placebo [n=321]). NASH resolution was achieved in 25.9% (80 mg) and 29.9% (100 mg) of resmetirom-treated versus 9.7% of placebo-treated patients (p<0.001 vs placebo). Fibrosis improvement was achieved in 24.2% (80 mg) and 25.9% (100 mg) of resmetirom-treated versus 14.2% of placebo-treated patients (p<0.001 vs placebo). Week 24, low-density lipoprotein cholesterol was reduced from baseline by -13.6% (80 mg) and -16.3% (100 mg) with resmetirom versus +0.1% placebo (p<0.001 vs placebo). Diarrhea and nausea were more frequent with resmetirom. Incidence of serious AEs was similar across treatment groups, 10.9%, 12.7%, and 11.5% in 80 mg, 100 mg and placebo groups respectively.
Conclusions: Both 80 and 100 mg doses of resmetirom were superior to placebo in ≥1 stage improvement in liver fibrosis as well as in resolution of NASH.
(Funded by Madrigal Pharmaceuticals; MAESTRO-NASH ClinicalTrials.gov identifier, NCT03900429)
Methods: MAESTRO-NASH is an ongoing Phase 3 trial in adults with biopsy-confirmed NASH and fibrosis stage 1B, 2, or 3. Patients were randomized 1:1:1 to once-daily resmetirom 80 mg, resmetirom 100 mg, or placebo. Dual primary endpoints at Week 52 were NASH resolution with ≥2-point reduction in the nonalcoholic fatty liver disease [NAFLD] activity score [NAS] and no worsening of fibrosis and ≥1-stage improvement in fibrosis with no worsening of NAS.
Results: Overall, 966 patients formed the primary analysis population (resmetirom 80 mg [n=322], resmetirom 100 mg [n=323], or placebo [n=321]). NASH resolution was achieved in 25.9% (80 mg) and 29.9% (100 mg) of resmetirom-treated versus 9.7% of placebo-treated patients (p<0.001 vs placebo). Fibrosis improvement was achieved in 24.2% (80 mg) and 25.9% (100 mg) of resmetirom-treated versus 14.2% of placebo-treated patients (p<0.001 vs placebo). Week 24, low-density lipoprotein cholesterol was reduced from baseline by -13.6% (80 mg) and -16.3% (100 mg) with resmetirom versus +0.1% placebo (p<0.001 vs placebo). Diarrhea and nausea were more frequent with resmetirom. Incidence of serious AEs was similar across treatment groups, 10.9%, 12.7%, and 11.5% in 80 mg, 100 mg and placebo groups respectively.
Conclusions: Both 80 and 100 mg doses of resmetirom were superior to placebo in ≥1 stage improvement in liver fibrosis as well as in resolution of NASH.
(Funded by Madrigal Pharmaceuticals; MAESTRO-NASH ClinicalTrials.gov identifier, NCT03900429)
| Original language | English |
|---|---|
| Pages (from-to) | 497-509 |
| Number of pages | 13 |
| Journal | The New England Journal of Medicine |
| Volume | 390 |
| DOIs | |
| Publication status | Published - 8 Feb 2024 |
Bibliographical note
Support Statement:The MAESTRO-NASH trial is sponsored by Madrigal Pharmaceuticals. Medical writing and editorial assistance was provided by Thomas R. King, MPH, Karen A. Finnegan, PhD and Keith J. Miller, PhD, employees of Madrigal Pharmaceuticals. We thank the patients, their families, and trial investigators for participating in this trial.
