Rezdiffra Demonstrates Cardiovascular and Liver Risk Reduction in MASH Patients
核心洞察
Rezdiffra significantly improved atherogenic lipid profiles including LDL-C, ApoB and Lp(a) in MASH (搜索) patients, with 37.5% of statin-treated patients achieving clinically meaningful Lp(a) reductions below 50mg/dL.
In patients with compensated MASH (搜索) cirrhosis (搜索), Rezdiffra treatment reduced high-risk classification for portal hypertension (搜索) from 75% to 54.5% over two years using the ANTICIPATE-NASH risk score.
Real-world evidence demonstrated that 49% of patients achieved ≥25% reduction in liver stiffness over nine months, with sustained improvements in liver enzymes and cardiometabolic parameters.
Madrigal Pharmaceuticals presented compelling new evidence at the European Association for the Study of the Liver (EASL) Congress 2026 demonstrating that Rezdiffra (resmetirom) reduces both cardiovascular and liver-related risk markers in patients with metabolic dysfunction-associated steatohepatitis (搜索) (MASH (搜索)). The data, spanning eight poster presentations, reinforces the drug's position as foundational therapy for MASH while revealing significant cardiovascular co-benefits.
Cardiovascular Risk Reduction Independent of Statin Therapy
A secondary analysis of the Phase 3 MAESTRO-NASH and MAESTRO-NAFLD-1 trials involving approximately 966 patients demonstrated that Rezdiffra 100mg significantly improved atherogenic lipid profiles regardless of baseline statin use. Among statin-treated patients (n=473), 44.4% of those with baseline LDL-C ≥70mg/dL shifted below that threshold at week 52, while 50.0% with baseline LDL-C ≥100mg/dL achieved levels below 100mg/dL.
The most striking findings emerged in lipoprotein(a) [Lp(a)] reduction, a cardiovascular risk factor largely unaffected by statin therapy. Among patients with elevated baseline Lp(a), 36.3% of those with levels ≥30mg/dL and 37.5% with levels ≥50mg/dL shifted below these thresholds. In statin-naive patients (n=493), the Lp(a) reductions were even more pronounced, with 62.5% of patients with baseline Lp(a) ≥50mg/dL crossing below that threshold by week 52.
"Cardiovascular disease (搜索) is the leading cause of death in people with MASH (搜索), so the secondary analysis from the Phase 3 MAESTRO program demonstrating that Rezdiffra improved LDL-C, ApoB and Lp(a) is highly relevant for clinicians and patients," said Dr. Meena B. Bansal, System Chief, Division of Liver Diseases Director at the MASH/NASH Center of Excellence, Icahn School of Medicine at Mount Sinai.
Portal Hypertension Risk Reduction in Cirrhosis Patients
In patients with well-compensated MASH (搜索) cirrhosis (搜索) (F4c), Rezdiffra demonstrated progressive improvements in the ANTICIPATE-NASH risk score, a noninvasive model that predicts clinically significant portal hypertension (搜索) (CSPH) risk and liver-related events. The analysis of 180 cirrhosis patients from the MAESTRO-NAFLD-1 open-label extension showed the proportion classified as high-risk for CSPH decreased from 75% at baseline to 60.3% at Year 1 and 54.5% at Year 2.
Mean ANTICIPATE-NASH scores declined by up to 37.6% over two years of treatment. Importantly, liver-related events were infrequent and occurred exclusively in patients with baseline ANTICIPATE-NASH scores associated with elevated CSPH risk, supporting the tool's utility for risk stratification and clinical decision-making.
Real-World Evidence Confirms Clinical Benefits
Multiple real-world analyses evaluating Rezdiffra use in routine clinical practice demonstrated sustained improvements across key parameters. In one analysis from a large gastroenterology practice, 48.6% of patients achieved ≥25% reduction in liver stiffness over a mean follow-up period of approximately nine months. Treatment discontinuation due to adverse events remained below 1%.
An electronic health record analysis of 728 patients treated over 12 months showed statistically significant reductions in ALT and AST liver enzymes, consistent across all subgroups regardless of baseline diabetes status, obesity, or concurrent GLP-1 and statin use. LDL-C levels also decreased significantly in the overall cohort.
A German prospective registry study identified that approximately one in five of 1,308 analyzed patients met criteria for Rezdiffra treatment based on noninvasive tests, with treatment-eligible patients showing higher distribution of three or more metabolic comorbidities simultaneously.
Clinical Implications for MASH Management
"New analyses from the Phase 3 MAESTRO program and a growing body of real-world evidence reinforce Rezdiffra's position as the foundational therapy for MASH (搜索)," said Dr. David Soergel, Chief Medical Officer of Madrigal. "The data we are presenting at the EASL Congress give us new insight into Rezdiffra's potential to reduce clinically significant portal hypertension (搜索) risk in patients with well-compensated MASH cirrhosis (搜索), a population with no approved therapies."
The cardiovascular benefits appear particularly significant given that MASH (搜索) is an independent driver of cardiovascular disease (搜索). Dr. Bansal noted that patients achieved key MASH endpoints and significant improvements in multiple atherogenic lipids regardless of baseline statin use, which is particularly important because statins are not known to meaningfully lower lipoproteins such as Lp(a).
Treatment Profile and Current Indications
Rezdiffra is indicated in conjunction with diet and exercise for treating adults with noncirrhotic MASH (搜索) with moderate to advanced liver fibrosis (搜索) (stages F2 to F3). The once-daily oral thyroid hormone receptor-β (搜索) agonist was the first medication approved for MASH treatment in both the U.S. and Europe.
In the pivotal Phase 3 MAESTRO-NASH biopsy trial, Rezdiffra achieved both fibrosis improvement and MASH (搜索) resolution primary endpoints while reducing liver stiffness, liver fat, liver enzymes and atherogenic lipids. At one year, 91% of patients treated with Rezdiffra 100mg achieved improvement or stabilization of liver stiffness.
The drug is not currently approved for patients with cirrhosis (搜索), though an ongoing Phase 3 outcomes trial is evaluating its use in compensated MASH (搜索) cirrhosis (F4c). The ANTICIPATE-NASH data may provide a pathway for potential label expansion in this high-risk population with significant unmet medical need.