MDGL News & Events

Madrigal Pharmaceuticals announced new analyses of Phase 3 data and real-world evidence demonstrating Rezdiffra reduced markers of cardiovascular and liver-related risk in patients with MASH. The data are featured across eight poster presentations at the European Association for the Study of the Liver Congress, taking place May 27-30 in Barcelona, Spain. Data from a secondary analysis of the Phase 3 MAESTRO-NASH and MAESTRO-NAFLD-1 trials demonstrated that Rezdiffra improved key histologic MASH endpoints and significantly reduced multiple atherogenic lipids and lipoproteins associated with cardiovascular risk, including LDL-C and Lp(a), regardless of baseline statin use. Among statin-treated patients receiving Rezdiffra 100mg: 44.4% of patients with baseline LDL-C greater than or equal to 70mg/dL shifted to less than 70mg/dL at week 52. In total, 50% of patients with baseline LDL-C greater than or equal to 100mg/dL shifted to less than 100mg/dL at week 52. Among patients with elevated baseline Lp(a), 36.3% of patients with baseline Lp(a) greater than or equal to30mg/dL and 37.5% of patients with baseline Lp(a) greater than or equal to50mg/dL shifted below those thresholds. No significant statin-related safety signals were observed. Among patients receiving Rezdiffra 100mg and no statins: 13.8% of patients with baseline LDL-C greater than or equal to 70mg/dL shifted to less than 70mg/dL at week 52. In total, 51.5% of patients with baseline LDL-C greater than or equal to 100mg/dL shifted to less than100mg/dL at week 52. Among patients with elevated baseline Lp(a), 45.4% of patients with baseline Lp(a) greater than or equal to30mg/dL and 62.5% of patients with baseline Lp(a) greater than or equal to 50mg/dL shifted below those thresholds. These findings support the concomitant use of Rezdiffra with statin therapy and suggest the potential for Rezdiffra to address both liver disease and cardiometabolic risk in patients with MASH. In patients with compensated MASH cirrhosis, clinically significant portal hypertension is a key driver of disease progression and severe liver-related complications. While Baveno criteria are used to identify patients likely to have CSPH, ANTICIPATE-NASH is a noninvasive risk stratification model developed for MASH that integrates liver stiffness measurements, platelet count and body mass index to estimate future CSPH risk and predict the likelihood of liver-related events over the subsequent three years. The ANTICIPATE-NASH risk model was applied to the open-label extension cohort from the MAESTRO-NAFLD-1 trial, which included patients with well-compensated MASH cirrhosis treated with Rezdiffra for up to two years. Results demonstrated progressive improvements in ANTICIPATE-NASH risk scores over time: the proportion of patients 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. Liver-related events were infrequent and occurred exclusively in patients with baseline ANTICIPATE-NASH scores associated with elevated CSPH risk. These findings support the potential use of ANTICIPATE-NASH as a risk stratification tool to identify patients with a high-risk of disease progression, informing prognosis and clinical decision-making.