New data from phase III MAESTRO-NASH biopsy clinical trial of MGL 3196 in NASH with liver fibrosis presented at NASH-TAG Conference.- Madrigal Pharma

In December 2022, Madrigal announced that MAESTRO-NASH achieved both liver histological improvement endpoints that FDA proposed as reasonably likely to predict clinical benefit to support accelerated approval for the treatment NASH with liver fibrosis. New data to be presented at NASH-TAG using a supportive analysis, a "consensus read" by the central pathologists of digitized biopsy images, supplement the positive topline findings and reinforce the strength of results observed in the primary analysis.

Additional MAESTRO-NASH biopsy results include: All baseline and Week 52 biopsies in MAESTRO-NASH were read independently by two central pathologists (glass slides) for the primary analysis read. Each pathologist's scores showed a similar statistically significant magnitude of response at both doses for both liver biopsy endpoints. The results were combined statistically to generate a single treatment effect.

As a supportive analysis, a “consensus read” of digitized biopsy images was conducted in cases where the two pathologists scores disagreed as to whether the there was a response for either NASH resolution (ballooning 0,1; at least 2-point NAS reduction and no worsening of fibrosis) OR at least 1 stage fibrosis reduction with no worsening of NAS (primary endpoints). The consensus read by the two central pathologists reinforced the positive results observed in the primary analysis. Other secondary liver biopsy endpoints were achieved at both doses including at least 2 point reduction in NAS (with at least 1 point improvement in ballooning and/or inflammation) and no worsening of fibrosis; at least 2 point reduction in NAS (with at least 1 point improvement in ballooning and/or inflammation) AND at least 1-stage improvement in fibrosis; NASH resolution (with at least 2 point reduction in NAS) AND at least 1-stage improvement in fibrosis; a 2-stage reduction in fibrosis without worsening of NAS; and reduction in all 3 NAS components (ballooning, inflammation and steatosis) without worsening of fibrosis (the steatosis response included at least 1-point improvement in biopsy steatosis grade and/or, for this endpoint only, a MRI-PDFF reduction of at least 30%). The new MAESTRO-NASH data are being presented at the NASH-TAG Conference, taking place from January 5-7, 2023 in Park City, Utah.

In the first half of 2023, Madrigal intends to file a new drug application seeking accelerated approval of resmetirom. In addition to the efficacy and safety results from MAESTRO-NASH, the filing will be supported by a robust safety database, which also includes the Phase III MAESTRO-NAFLD-1 safety study, and two ongoing outcomes studies designed to confirm clinical benefit.