Patients were randomized to receive either MGL-3196 or placebo in a 2:1 ratio.
The study met the primary endpoint at week 12 and demonstrated a sustained treatment benefit at week 36.
In the study, more patients treated with MGL-3196 compared with placebo achieved a two point reduction in NAS (NAFLD activity score) on biopsy.
The company said a ≥30% fat reduction in MGL-3196 treated patients, at week 12 predicted an enhanced NASH histologic response at week 36, including 39% NASH resolution, which was statistically significant relative to placebo.
MGL-3196 was well-tolerated with mostly mild and lesser moderate adverse events.
Madrigal CEO Paul Friedman said: “The degree of NASH resolution, an approvable FDA endpoint, in patients who received MGL-3196 for 9 months we believe suggests a high likelihood of success in a larger trial with a somewhat longer treatment period in a Phase 3 study designed similarly to this Phase 2 study, pending regulatory agreement with such a design.
“Further, considering what we have learned regarding drug exposure and dosing, we believe there is potential to resolve NASH in as little as 9 months in 30-40% of patients receiving only MGL-3196, a well-tolerated once a day oral therapy.”
Madrigal said it looks forward to advance MGL-3196 in a phase 3 clinical trial in NASH patients.
The company noted that MGL- 3196 demonstrated the potential for a range of of therapeutically beneficial effects, enhancing components of both metabolic syndrome, like insulin resistance and dyslipidemia, and fatty liver disease, including lipotoxicity and inflammation.
Image: Madrigal’s MGL-3196 achieved liver biopsy endpoints in patients with NASH. Photo: courtesy of jk1991 / FreeDigitalPhotos.net.