Topline Results Positive for Safety of NAFLD Treatment

New topline results show resmetirom is safe and well-tolerated in patients with non-alcoholic fatty liver disease (NAFLD).

Madrigal Pharmaceuticals announced the positive results from the placebo-controlled, double-blind portion of the MAESTRO-NAFLD-1 safety study.

In the 52-week study, patients were treated with resmetirom 80 mg and 100 mg once daily.

The drug was also effective treating patients with presumed non-alcoholic steatohepatitis (NASH), resulting in significant, clinically relevant reductions in liver fat and atherogenic lipids.

The Treatment

Resmetirom is a thyroid hormone that activates β-receptor in hepatocytes, which plays a role in liver function.

“This positive readout from MAESTRO-NAFLD-1 is a significant milestone for the field,” Stephen Harrison, MD, Medical Director for Pinnacle Clinical Research, San Antonio, Texas, Visiting Professor of Hepatology, Oxford University, and Principal Investigator of the MAESTRO studies, said in a statement. “As the first Phase 3 study in NASH that does not rely on liver biopsy to identify patients and measure treatment response, MAESTRO-NAFLD-1 will help accelerate the role of non-invasive imaging and biomarkers in NASH drug development.”

The Study

The study involved 972 patients who were randomized to receive either resmetirom or placebo, 969 of which were included in the safety population and 943 of which were included in a modified intent-to-treat population for the evaluation of key secondary and other endpoints.

Patients included in the study had the presence of 3 risk factors of Metabolic Syndrome, a level of liver fibrosis consistent with a range of stages of liver fibrosis, and at least 8% liver fat.

In addition, any occurrence of less than 25 events of an individual safety measurement was blinded by treatment group.

Safety

The treatment was safe and well-tolerated at the 80 mg and 100 mg with adverse events reported to be generally mild or moderate in severity.

Also, the frequency of serious adverse events was similar across the different treatment arms and discontinuation because of adverse events was low.

Serious adverse events occurred at the expected rates of the patient population.

The most common adverse event was generally mild diarrhea or increased stool frequency at the beginning of therapy. This occurred in 9% and approximately 17% over the placebo rate in the 80 mg and 100 mg dose groups, respectively.

Both groups achieved hierarchically-controlled key secondary endpoints. The drug resulted in significant reductions in liver fat, measured by MRI-PDFF and reduced atherogenic lipids, including LDLc, apolipoprotein B and triglycerides.

The investigators also found lipid reductions were numerically greater in the higher dose open label treatment arm compared to the 100 mg double-blind arm.