Primary results from MAESTRO-NASH trial: resmetirom efficacious for NASH

Resmetirom proved efficacious in the treatment of non-alcoholic steatohaepatitis (NASH) and has shown improvement in fibrosis. Together with the agent's acceptable safety profile, resmetirom offers a useful oral therapy for patients with NASH.

Resmetirom is an investigational, liver-targeted thyroid hormone receptor-β (THR-β) agonist. In a phase 2 trial, this agent showed promising activity in participants with NASH and fibrosis [1]. Building on these findings, the double-blind, placebo-controlled, phase 3 MAESTRO-NASH trial (NCT03900429) randomised adult participants with biopsy-confirmed NASH and fibrosis (n=966) in a 1:1:1 ratio to 3 groups: placebo, resmetirom 100 mg, or resmetirom 80 mg, once daily [2].

Prof. Jörn Schattenberg (University Medical Center Mainz, Germany) mentioned that participants needed to have at least 3 metabolic risk factors and ≥8% hepatic fat measured by magnetic resonance imaging-proton density fat fraction to be eligible for the study. The dual primary endpoint at week 52 was NASH resolution with no worsening of fibrosis or ≥1-stage improvement in fibrosis with no worsening in the non-alcoholic fatty liver disease (NALFD) activity score. According to Prof. Schattenberg, about 60% of the participants had type 3 fibrosis, and around 14% and 47% were on baseline GLP-1 receptor agonists and/or statins, respectively. Prof. Schattenberg presented the primary findings of the trial at 52 weeks.

Both the 80 mg and the 100 mg arms significantly outperformed the placebo arm in terms of NASH resolution, with 26% and 30% of the participants achieving this endpoint in the active arms compared with 10% of the participants in the latter arm (P<0.0001 for both). Similarly, a significantly larger proportion of participants in the resmetirom arms reached ≥1-stage improvement in fibrosis, with 24% in the 80 mg arm (P=0.0002) and 26% in the 100 mg arm (P<0.0001), compared with 14% of patients in the placebo arm. Prof. Schattenberg added that participants in the 80 and 100 mg arms had a mean percentage change in low-density lipoprotein (LDL) cholesterol of -14% and -16%, respectively, whereas this change was 0% in participants on placebo (see Figure).

Figure: Dual primary endpoints and key secondary endpoint at week 52



NASH, non-alcoholic steatohaepatitis; LDL, low-density lipoprotein.

The safety profile did not show any concerns. Prof. Schattenberg mentioned that the treatment-emergent adverse event-related discontinuation rate was somewhat higher in the 100 mg arm (6.8%) compared with the 80 mg arm (1.9%) or the placebo arm (2.5%), but this trend was only visible during the first 12 weeks of the study. Diarrhoea (30%) and nausea (20%) were the most common treatment-emergent adverse events in the active arms.

In conclusion, these results from the MAESTRO-NASH trial support resmetirom as a potential treatment for patients with NASH.

1. 
   
   1. Harrison SA, et al. Lancet. 2019;394(10213):2012–2024.
   2. Schattenberg J, et al. A randomized controlled phase 3 trial of resmetirom in nonalcoholic steatohepatitis: 52-week data from MAESTRO-NASH. OP001, UEG Week 2023, 14–17 October, Copenhagen, Denmark.

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Posted on 7 December, 20237 December, 2023