Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL), announced that Dr. Stephen Harrison, M.D., Medical Director for Pinnacle Clinical Research, San Antonio, Texas, and Visiting Professor of Hepatology, Oxford University, and Principal Investigator of the MAESTRO studies, will make an oral presentation today at 4:30 PM ET at The Liver Meeting Digital Experience™, The American Association for the Study of Liver Diseases Meeting, November 2020 accessible via the Product Theaters and Satellite Symposium page. Dr. Harrison’s presentation, based on data from studies with MGL-3196 (resmetirom), will also highlight key insights from three posters, which are available to registered attendees on The Liver Meeting Digital Experience™ website throughout the four-day meeting. Resmetirom is the first orally administered, small-molecule, liver-directed, truly β-selective thyroid hormone receptor (THR) agonist and is currently in Phase 3 development for the treatment of NASH patients both with biopsy-confirmed fibrosis stage 2-3 (ClinicalTrials.gov NCT03900429) and in presumed NASH subjects diagnosed non-invasively (ClinicalTrials.gov/NCT04197479).
Dr. Harrison commented, “In the MAESTRO-NASH study, using a series of readily available tests such as FibroScan, MRI-PDFF and PRO-C3 in patients with metabolic risk factors (diabetes, obesity, dyslipidemia and hypertension) we have demonstrated that, in recruiting a clinical trial, NASH with advanced fibrosis (F2-F3) may be confirmed on liver biopsy with an increasing level of confidence. The MAESTRO-NAFLD-1 study in patients with presumed NASH diagnosed non-invasively, now with 1,200 enrolled patients, is helping to build a robust safety and efficacy data set in NASH patients treated with resmetirom.”
Becky Taub, M.D., Chief Medical Officer and President of Research & Development of Madrigal, stated, “Interim data from the ongoing open label arm of MAESTRO-NAFLD-1 confirm the safety and efficacy at a 100 mg dose of resmetirom, with 80% of patients achieving at least a 30% reduction from baseline in liver fat measured on MRI-PDFF, and more than half achieving a 50% or greater reduction in liver fat at Week 16, both of which percentage fat reductions have been associated with increased NASH resolution and reduction in liver fibrosis on subsequent liver biopsy in resmetirom treated patients. The reduction in MRE at Week 16 is novel, and consistent with potential fibrosis and inflammation reductions in patients with baseline F1-F3 fibrosis. MRE is potentially a more accurate measurement of liver fibrosis than other non-invasive measures such as FibroScan because MRE measures a larger area of the liver, and may demonstrate correlations with Week 52 liver biopsy in MAESTRO-NASH. Of note, no safety flags have been observed at the 100 mg dose in the open-label arm, consistent with earlier Phase 1 and Phase 2 data.”
Paul Friedman, M.D., Madrigal’s Chief Executive Officer, added, “The open label arm of MAESTRO-NAFLD-1 provides opportunities to observe safety and the potential benefits of resmetirom treatment on an ongoing basis in non-cirrhotic NASH and compensated NASH cirrhotic patients, with completion of the double-blind arms of the study in the next 12 months. We believe that these data will inform the results of the blinded 80 and 100 mg arms of the MAESTRO-NAFLD-1 and MAESTRO-NASH studies.”
- #1657 ALGORITHM FOR PREDICTING ADVANCED NASH FIBROSIS ON SCREENING BIOPSY IN RESMETIROM PHASE 3 MAESTRO-NASH CLINICAL TRIAL
Dr. Stephen A Harrison1, Dr. Rebecca A. Taub2, Prof. Morten Asser Karsdal3, John Franc2, Dr. Mustafa R Bashir4, Mr. Jordan Mark Barbone2, Dr. Guy Neff5, Dr. Nadege T Gunn1 and Dr. Sam Moussa6, (1) Pinnacle Clinical Research, (2) Madrigal Pharmaceuticals, (3) Biomarkers & Research, Nordic Bioscience, (4) Department of Radiology, Duke University Medical Center, (5) Covenant Research, LLC, (6) Medical, Adobe Gastroenterology
MAESTRO-NASH is a Phase 3 double-blind placebo-controlled serial liver biopsy study to evaluate resmetirom for the treatment of NASH with F2 or F3 fibrosis and an exploratory F1 arm. Data was assessed for the power of the screening paradigm to predict eligible NASH with fibrosis on liver biopsy. These data suggest that PRO-C3 is a marker not only of fibrosis stage in NASH but also of the level of NASH activity (inflammation and ballooning) in the NASH liver. In the absence of a liver biopsy, elevated PRO-C3 in the setting of metabolic syndrome (or FIBC3 (PRO-C3 [age, BMI, platelets, T2D]), fibroscan and MRI-PDFF may predict advanced NASH.
- #1707 TREATMENT WITH RESMETIROM IN PHASE 3 MAESTRO-NAFLD-1 NASH STUDY OPEN LABEL ARM: EFFECTS ON BIOMARKERS AND IMAGING
Dr. Stephen A Harrison, Pinnacle Clinical Research, Dr. Naim Alkhouri, Arizona Liver Health, Dr. Rebecca A. Taub, Madrigal Pharmaceuticals, Dr. Guy Neff, Covenant Research, LLC, Dr. Seth J Baum, Excel Medical Clinical Trials and Dr. Mustafa R Bashir, Department of Radiology, Duke University Medical Center Data from the ongoing Open Label Arm of Madrigal’s MAESTRO-NAFLD-1 trial will be presented.
In this 52-week Phase 3 open label study, NASH patients identified using non-invasive imaging and biomarkers were treated with resmetirom 100 mg and demonstrated rapid reduction in hepatic fat, biomarkers and atherogenic lipids after 12-16 weeks of treatment, potentially supporting use of non-invasive tests to monitor individual NASH patient response to resmetirom treatment.
|Relative % Change||-53%||-62%|
|Baseline (>2.9, F1-F3)||3.5||3.5|
- #1675 IMPROVEMENT OF HEALTH-RELATED QUALITY OF LIFE IS ASSOCIATED WITH IMPROVEMENT OF FAT FRACTION BY MRI-PDFF IN PATIENTS WITH NONALCOHOLIC STEATOHEPATITIS TREATED WITH RESMETIROM
Dr. Zobair M. Younossi, MD, MPH, FAASLD1, Maria Stepanova2, Dr. Rebecca A. Taub3, Mr. Jordan Mark Barbone3, Dr. Sam Moussa4and Dr. Stephen A Harrison5, (1) Center for Liver Disease, Department of Medicine, Inova Health System, (2) Center for Outcomes Research in Liver Diseases, Washington, DC, United States, (3) Madrigal Pharmaceuticals, (4) Medical, Adobe Gastroenterology, (5) Pinnacle Clinical Research
A review of patient reported outcome data from resmetirom’s Phase 2 NASH study demonstrates that NASH patients treated with resmetirom who had liver fat reduction also improved some quality of life measures, particularly physical components such as bodily pain. Ongoing Phase 3 studies will assess long-term sustainability of quality of life improvements with resmetirom treatment.