MDGL - Madrigal Pharmaceuticals Announces New Data from the Phase 3 MAESTRO-NASH Study of Rezdiffra™ (resmetirom) Presented at the EASL Congress | Benzinga
- Late-breaking AI-based analysis of MAESTRO-NASH biopsy data demonstrates Rezdiffra improved key fibrotic features that are predictive of progression to decompensated cirrhosis
- Noninvasive test data through three years of treatment demonstrate durable treatment response to Rezdiffra; 91% of patients achieved improvement or stabilization of liver stiffness
- First analysis of health-related quality of life data from MAESTRO-NASH demonstrates Rezdiffra improved patient worry, health distress and stigma
- First analysis of Rezdiffra treatment in MetALD demonstrates patients achieved similar rates of fibrosis improvement and steatohepatitis resolution compared to the NASH population
CONSHOHOCKEN, Pa., June 06, 2024 (GLOBE NEWSWIRE) -- Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL), a biopharmaceutical company focused on delivering novel therapeutics for nonalcoholic steatohepatitis (NASH), today announced results from new analyses of the Phase 3 MAESTRO-NASH trial of Rezdiffra being presented at the EASL Congress, which takes place from June 5-8, 2024 in Milan, Italy.
Rezdiffra is a once-daily, oral, liver-directed thyroid hormone receptor (THR)-? agonist designed to target key underlying causes of NASH. It is the first approved medication for the treatment of NASH. In the pivotal Phase 3 MAESTRO-NASH biopsy trial, Rezdiffra achieved both fibrosis improvement and NASH resolution primary endpoints, and 80% of patients treated with Rezdiffra 100 mg experienced improvement or stabilization of fibrosis. Rezdiffra is indicated in conjunction with diet and exercise for the treatment of adults with noncirrhotic NASH with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis). Continued approval for this indication may be contingent upon verification and description of clinical benefit in ongoing confirmatory trials.
Bill Sibold, Chief Executive Officer of Madrigal, stated, "The ten abstracts Madrigal will be presenting at the EASL Congress further advance our leadership position in NASH. Our late-breaking oral presentation leverages innovative AI technology to provide deeper insight into the antifibrotic effects of Rezdiffra and the critical role of THR-? as a suppressor of NASH disease progression. This analysis is particularly meaningful in light of emerging health economics data indicating patients with NASH can progress more rapidly than previously thought to decompensated cirrhosis. Additionally, new analyses of the MAESTRO-NASH data broaden our understanding of Rezdiffra treatment response across a range of parameters, including noninvasive measures of fibrosis and steatosis through three years of therapy and health-related quality of life. These data reinforce Rezdiffra's role as the foundational therapy in NASH."
Becky Taub, M.D., Chief Medical Officer and President of Research & Development of Madrigal, added, "Madrigal continues to advance ambitious scientific research that will help shape the future of the NASH field. We also look forward to presenting our first abstract examining Rezdiffra treatment in patients with probable metabolic dysfunction and alcohol-associated liver disease (MetALD), a population that has historically been underrepresented in clinical research."
Late-breaking AI-based analysis of MAESTRO-NASH biopsy data demonstrates Rezdiffra improved key fibrotic features that may be predictive of progression to decompensated cirrhosis
An AI-driven fibrosis assessment methodology, qFibrosis (Histoindex), has identified 30 specific fibrotic features on NASH liver biopsies that may be predictive of progression to cirrhosis and decompensated cirrhosis based on the SteatoSITE database. SteatoSITE contains integrated clinical and pathological data from 940 cases across the NASH spectrum with outcome data from electronic health record and pathologist-assigned fibrosis stage and RNA on baseline biopsy.
In an analysis of MAESTRO-NASH data featured in a late-breaking presentation at EASL, total qFibrosis score showed a highly significant improvement in fibrosis with Rezdiffra treatment and less progression of fibrosis as compared with placebo; results were similar to pathologist scoring. Six qFibrosis progression features with the strongest correlations between baseline pathologist scoring and noninvasive tests were identified. At week 52, patients treated with Rezdiffra showed reduction from baseline in these key features compared to placebo, with the most marked reductions occurring in the F3 population.
In a previous study, baseline biopsy RNA analyses and annotated patient timelines from SteatoSITE in histologically identical high risk fibrosis stages (F3 and F4) identified THR-? as a potential master regulator of fibrosis progression. Patients with low THR-? activity in their liver at baseline had the highest chance of progression to decompensated cirrhosis.
"The qFibrosis data provide support for Rezdiffra's potential in benefiting patients with NASH with moderate to advanced liver fibrosis by reversing fibrosis and preventing progression to more advanced liver disease," said Jörn M. Schattenberg, M.D., Professor of Medicine and Director of the Department of Medicine at the University Medical Center Homburg and University of the Saarland in Germany. "These results, coupled with earlier analyses of the SteatoSITE database which found that reduced THR-? activity predicts future hepatic decompensation in patients with NASH, are highly encouraging as we await results from two ongoing Phase 3 outcomes studies of Rezdiffra, a THR-? agonist."
Noninvasive test data through three years of treatment demonstrate durable treatment response to Rezdiffra
In analyses of noninvasive test results from MAESTRO-NASH, changes in vibration-controlled transient elastography (VCTE; an ultrasound-based measure of liver stiffness, a surrogate for fibrosis), controlled attenuation parameter (CAP; an ultrasound-derived measure of fat content in the liver), and magnetic resonance imaging-proton density fat fraction (MRI-PDFF; an MRI-based measure of triglyceride content in the liver) were assessed in the Rezdiffra 80mg, Rezdiffra 100mg, ...