Madrigal Reports Positive Quality of Life Results from Phase 3 MAESTRO-NASH Trial of Rezdiffra

Madrigal Pharmaceuticals, Inc. recently announced positive findings from a study on Rezdiffra (resmetirom), an innovative treatment for nonalcoholic steatohepatitis (NASH) with moderate to advanced fibrosis. Published in the journal Hepatology, the data revealed significant improvements in health-related quality of life (HRQL) for patients.

Rezdiffra, a once-daily oral medication, is a thyroid hormone receptor (THR)-β agonist specifically aimed at addressing the root causes of NASH. It has the distinction of being the first FDA-approved drug for NASH treatment. In a pivotal Phase 3 MAESTRO-NASH biopsy trial, Rezdiffra met primary endpoints of both fibrosis improvement and NASH resolution. Notably, 80% of patients on a 100 mg dose showed either improvement or stabilization of fibrosis. Rezdiffra is prescribed along with diet and exercise for adults with noncirrhotic NASH and moderate to advanced liver fibrosis (stages F2 to F3).

Dr. Zobair M. Younossi, the lead author of the HRQL analysis and Chairman of the Global NASH Council, emphasized the often overlooked but significant impact of NASH on patients' quality of life. Symptoms like fatigue and lack of stamina severely impair HRQL. The study's findings that Rezdiffra led to meaningful and statistically significant improvements across multiple HRQL domains are therefore highly encouraging. Importantly, no worsening of HRQL related to Rezdiffra's side effects was observed, highlighting the medication's tolerability.

The study assessed changes in HRQL scores from baseline in patients treated with Rezdiffra compared to those given a placebo. By weeks 24 and 52, improvements in the Worry domain of the Chronic Liver Disease Questionnaire-NASH were evident in patients taking Rezdiffra. At week 52, those who experienced fibrosis improvement or NASH resolution reported enhanced HRQL in various domains, including Health Distress and Stigma. These benefits were not seen in the placebo group. Patients with more advanced fibrosis (stage F3) showed improvements similar to or greater than those with less severe fibrosis (F2 or F1B).

Bill Sibold, CEO of Madrigal, highlighted the severe emotional toll NASH takes on patients, given its status as the leading cause of liver transplants among women and those listed for hepatocellular carcinoma in the U.S. The unpredictable progression of the disease adds to this distress. Rezdiffra's approval offers new hope, as evidenced by the improvements in HRQL seen in the MAESTRO-NASH trial.

NASH, a severe form of nonalcoholic fatty liver disease (NAFLD), is a leading cause of liver-related deaths and poses a growing burden on global healthcare systems. Patients with NASH, particularly those with advanced metabolic risk factors like hypertension and type 2 diabetes, face increased risks of cardiovascular events and other complications. Once the disease progresses to moderate or advanced liver fibrosis (stages F2 to F3), the risk of adverse liver outcomes rises significantly. NASH is rapidly becoming the leading cause of liver transplants in the U.S., especially among women.

Madrigal estimates that around 1.5 million people in the U.S. have been diagnosed with NASH, with about 525,000 of these cases involving moderate to advanced liver fibrosis. The company's initial focus for Rezdiffra will be on approximately 315,000 diagnosed patients receiving care from liver specialists.

In 2023, medical societies and patient groups worldwide renamed NASH to metabolic dysfunction-associated steatohepatitis (MASH) to reduce stigma and better represent the condition. Similarly, NAFLD was renamed metabolic dysfunction-associated steatotic liver disease (MASLD).

Rezdiffra is prescribed along with lifestyle changes to treat adults with NASH and moderate to advanced liver fibrosis. Its safety and efficacy in children are not established, and ongoing studies aim to confirm its clinical benefits. Patients with other liver issues, gallbladder problems, or those who are pregnant or breastfeeding should consult their healthcare provider before using Rezdiffra. The medication may interact with other drugs, necessitating careful management.

Common side effects of Rezdiffra include diarrhea, nausea, itching, abdominal pain, vomiting, dizziness, and constipation. Serious side effects could include liver injury and gallbladder problems, necessitating immediate medical attention.

Madrigal Pharmaceuticals continues to develop novel treatments for NASH, aiming to meet the significant unmet needs associated with this liver disease.