Phase III MAESTRO-NAFLD-1 study of MGL 3196 in NASH presented at International Liver Congress (EASL 2022).- Madrigal Pharmaceuticals

105 patients with well-compensated NASH cirrhosis were enrolled in the open-label arm of the phase III MAESTRO-NAFLD-1 study. Baseline FibroScan VCTE (kPa 24.6) and MRE (5.7) scores were consistent with F4 fibrosis. Patients with lower MRI-PDFF (at least 5%) at baseline had more progressed cirrhosis and greater spleen volumes.

Similar to patients with non-cirrhotic NASH, liver volume was greatly elevated compared to normal at baseline. Resmetirom reduced MRI-PDFF and LDL-C and other atherogenic lipids in patients with NASH cirrhosis and reduced FibroScan controlled attenuation parameter (CAP), VCTE, and MRE in a significant fraction of patients. The largest reduction in FibroScan VCTE (mean reduction of 9 kPa) occurred in the more advanced group (baseline PDFF at least 5%). Similar improvements were observed in MRE. 73% of patients, independent of baseline cirrhosis severity, had at least 15% reduction in liver volume at Week 52. Spleen volume was also reduced and was strongly correlated with liver volume change and exposure to resmetirom. Reductions in liver enzymes and atherogenic lipids were similar across patient subgroups.

Resmetirom was safe and well tolerated. As observed in patients with noncirrhotic NASH, mild GI adverse events were seen at the beginning of therapy. No differences in safety parameters between patients with cirrhosis compared to noncirrhotic NASH patients were noted. No thyroid axis changes or hyper- or hypothyroid symptoms were observed.