Relationship of non-invasive measures with histological response in patients with nonalcoholic steatohepatitis and fibrosis: 52-week data from the Phase 3 MAESTRO-NASH trial

Background 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 80mg, resmetirom 100mg, or placebo administered once daily. Histologic endpoints were assessed after 52 weeks. Dual primary endpoints at Week 52 were achieved with both resmetirom 80mg and 100mg: NASH resolution with no worsening of fibrosis (NR) or≥1-stage reduction in fibrosis with no worsening of NAS (FR).

Methods The relationship of non-invasive measures with histological response (NR and/or FR) in the resmetirom 80mg, resmetirom 100mg, and placebo groups was assessed.

Results Patients with biopsy-confirmed NASH with fibrosis had high metabolic risk. Among patients treated with resmetirom 80mg or 100mg who achieved a≥30% reduction from baseline in MRI-PDFF, NR was observed in 28% and 38% and FR in 17% and 18% more patients than placebo. A≥30% PDFF response was observed in 96%, 88%, and 92% of resmetirom 100mg NR, FR, and NR and/or FR responders. Half of resmetirom≥30% PDFF responders without NR or FR showed≥2-point NAS reduction. On biopsy, NR correlated (r2) with FR (=0.30). Additional correlates (r2) of NR and FR at resmetirom 100mg included reduction in PDFF (0.39, 0.23); ALT (0.20, 0.24); and liver volume (0.25, 0.18).

Conclusion Achievement of NASH resolution and fibrosis reduction was associated with a≥30% reduction from baseline in MRI-PDFF – at both resmetirom doses (80 and 100mg). Additional analyses are ongoing.

Publication History

Article published online:
23 January 2024