Madrigal Pharmaceuticals announced the publication of positive data from the Phase 3 MAESTRO-NASH trial, revealing that Rezdiffra (resmetirom) significantly improved health-related quality of life (HRQL) in patients with nonalcoholic steatohepatitis (NASH) and moderate to advanced fibrosis. The findings, published in Hepatology, highlight the potential of Rezdiffra, the first FDA-approved medication for NASH, to address the disease's impact on patients' emotional well-being.
Impact on Patient-Reported Outcomes
The MAESTRO-NASH trial evaluated changes in HRQL scores in patients receiving Rezdiffra versus placebo. By weeks 24 and 52, patients on Rezdiffra experienced notable improvements in the Worry domain of the Chronic Liver Disease Questionnaire-NASH. At week 52, patients who achieved fibrosis improvement or NASH resolution showed improvements in Worry, Health Distress, and Stigma domains. Zobair M. Younossi, M.D., MPH, FACP, FACG, AGAF, FAASLD, emphasized that NASH significantly impairs HRQL with symptoms like fatigue and lack of stamina, making these improvements highly encouraging.
Tolerability Profile
The study also highlighted Rezdiffra's tolerability, with no worsening of HRQL related to potential side effects. This is particularly important given the chronic nature of NASH and the need for long-term treatment options. The positive tolerability profile supports the use of Rezdiffra as a viable therapy for patients with NASH and moderate to advanced fibrosis.
Clinical Significance
Bill Sibold, CEO of Madrigal, noted that NASH is a leading cause of liver transplant among women and those listed for hepatocellular carcinoma in the U.S. He added that the unpredictable speed of NASH progression can cause serious emotional distress. The introduction of Rezdiffra offers hope for patients, reflected in the observed improvements in HRQL within the MAESTRO-NASH trial.
About Rezdiffra
Rezdiffra is a once-daily, oral, liver-directed thyroid hormone receptor (THR)-β agonist designed to target key underlying causes of NASH. It is indicated in conjunction with diet and exercise for adults with noncirrhotic NASH and moderate to advanced liver fibrosis (stages F2 to F3). The approval is contingent upon verification and description of clinical benefit in ongoing confirmatory trials.
NASH Disease Burden
NASH, also known as metabolic dysfunction-associated steatohepatitis (MASH), is a progressive form of nonalcoholic fatty liver disease (NAFLD) and a leading cause of liver-related mortality. Madrigal estimates that approximately 1.5 million patients have been diagnosed with NASH in the U.S., with about 525,000 having moderate to advanced liver fibrosis.
