• Data to be featured in an oral presentation at the American Association for the Study of Liver Diseases (AASLD) Liver Meeting®
• Analyses from comprehensive set of noninvasive tests used in MAESTRO-NASH provide new insights on strategies to identify patients and measure response to resmetirom
• A significant majority (>70%) of patients treated with resmetirom 100 mg experienced a ≥30% reduction in MRI-PDFF, which predicted treatment response on biopsy, including both the NASH resolution and fibrosis improvement endpoints
• Multiple additional abstracts examine resmetirom safety and efficacy in NASH with significant fibrosis and NASH with compensated cirrhosis

CONSHOHOCKEN, Pa., Nov. 10, 2023 (GLOBE NEWSWIRE) -- Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL), a clinical-stage biopharmaceutical company pursuing novel therapeutics for nonalcoholic steatohepatitis (NASH), today announced new data from the Phase 3 MAESTRO-NASH trial demonstrating broad treatment effects of resmetirom on noninvasive tests that may be used to monitor NASH with liver fibrosis. The noninvasive testing data and multiple additional abstracts from the MAESTRO program are being presented at the American Association for the Study of Liver Diseases (AASLD) Liver Meeting, taking place in Boston from November 10-14, 2023.

Resmetirom is a liver-directed thyroid hormone receptor (THR)-β agonist oral therapy that is designed to target key underlying causes of NASH. It is the only investigational therapy for NASH that has achieved both fibrosis improvement and NASH resolution primary endpoints in a Phase 3 trial.

In MAESTRO-NASH, resmetirom treatment helped patients with NASH with significant fibrosis (F2/F3) as diagnosed on liver biopsy achieve improvements in liver enzymes, magnetic resonance imaging-proton density fat fraction (MRI-PDFF), magnetic resonance elastography (MRE), FibroScan Vibration Controlled Transient Elastography (VCTE), FibroScan Controlled Attenuation Parameter (CAP), and the Enhanced Liver Fibrosis (ELF) test. Resmetirom also reduced levels of LDL cholesterol and other lipids that are associated with heart disease.

Rohit Loomba, M.D., Chief of the Division of Gastroenterology and Hepatology at University of California San Diego School of Medicine and lead author of the new MAESTRO-NASH analysis, stated, "These new data from MAESTRO-NASH highlight the importance of noninvasive tests in the care pathway for NASH with significant liver fibrosis and further improves our understanding of resmetirom's liver-directed efficacy as a THR-β agonist. In our analyses, resmetirom-mediated reduction in liver fat as measured by MRI-PDFF, a noninvasive imaging test, was the strongest predictor of both NASH resolution and fibrosis improvement on biopsy. This suggests that reducing liver fat with a THR-β agonist may resolve the underlying hepatitis that drives the disease and reverse or halt the fibrosis progression that leads to negative patient outcomes."

Becky Taub, M.D., Chief Medical Officer and President of Research & Development of Madrigal, stated, "It is encouraging to see such a broad and consistent treatment response with resmetirom across multiple noninvasive tests, from simple blood-based tests that are widely used in clinical practice today to advanced imaging tests that will play a larger role in future care pathways for NASH. If resmetirom receives accelerated approval, clinicians will have many opportunities to highlight treatment response for their patients over time; even something as readily measurable as an improvement in ALT or LDL can be highly motivating for patients and support treatment adherence."

A significant majority (>70%) of patients treated with resmetirom 100 mg had a ≥30% MRI-PDFF response. A ≥30% MRI-PDFF reduction was strongly associated with NASH resolution (96% of patients) and fibrosis improvement (88% of patients). Median reduction in MRI-PDFF was 52% overall in this group.

Resmetirom is an investigational therapy and has not been approved by the FDA or any other regulatory authority. In September 2023, the FDA granted Priority Review for the new drug application (NDA) seeking accelerated approval of resmetirom for the treatment of NASH with liver fibrosis and assigned a Prescription Drug User Fee Act date for resmetirom of March 14, 2024.

Artificial Intelligence-Based Analyses of MAESTRO-NASH Biopsy Results

A second oral presentation from the MAESTRO program examined the use of an artificial intelligence (AI) biopsy reading method (HistoIndex Second Harmonic Generation "qFibrosis" score) to measure the effect of resmetirom on fibrosis on serial liver biopsy using both continuous and quantitative scoring. In this analysis, AI-based reading of the biopsies reinforced the primary results from the central pathologists: measurements of fibrosis change using qFibrosis on either a continuous or categorical scale demonstrated a clear improvement and less worsening in fibrosis among resmetirom-treated patients as compared with placebo-treated patients after 52 weeks. A late-breaking poster examining another AI-based biopsy reading method (PathAI "AIM-NASH") also recapitulated the MAESTRO-NASH primary endpoint results and showed a high degree of alignment with pathologists on NASH component scoring.

Full Listing of Resmetirom Data Presentations at AASLD

Multiple resmetirom and Madrigal health economics outcomes research abstracts will be presented at the AASLD Liver Meeting:

• Oral presentation: "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" [Monday, November 13 at 8:30 AM. Presenter: Rohit Loomba]
• Oral presentation: "Artificial Intelligence to Measure Fibrosis Change on Liver Biopsy in MAESTRO-NASH: A Phase 3 Serial Liver Biopsy Study in 966 Patients with NASH Treated with Resmetirom or Placebo" [Sunday, November 12 at 11:00 AM. Presenter: Stephen Harrison]
• Late-Breaking poster: "Artificial Intelligence-Based Measurement of NASH Histology (AIM-NASH) Recapitulates Primary Results from Phase 3 Study of Resmetirom for Treatment of NASH/MASH" [Presenter: Janani Iyer]
• Poster of Distinction: "Resmetirom Treatment Helps Restore Thyroid Hormone Levels in Patients with Nonalcoholic Steatohepatitis: 52-Week Data from the Phase 3 MAESTRO-NASH Trial" [Presenter: Stephen Harrison]
• Poster: "Resmetirom Improves the Atherogenic Lipid/Lipoprotein Profile in Patients with Nonalcoholic Steatohepatitis: 52-Week Data from the Phase 3 MAESTRO-NASH Trial" [Presenter: Naim Alkhouri]
• Poster: "The Next Generation of HepQuant Tests Measure Reduction in Risk for Clinical Events in Compensated NASH Cirrhosis Subjects Treated with Resmetirom" [Presenter: Michael McRae]
• Poster: "Understanding the Incremental Costs of Nonalcoholic Steatohepatitis and Diabetes Using Electronic Health Records and Closed Claims Data" [Presenter: Jesse Fishman]
• Poster: "Characterizing the Management of Patients with NASH (With Versus Without Cirrhosis) in Real-World Clinical Practice: Rare Assessment by Hepatologists and Low Frequency of Imaging" [Presenter: Christina Qian]