Patients with non-alcoholic fatty liver disease (NAFLD) and suspected non-alcoholic steatohepatitis (NASH) achieved pivotal primary results in a 52-week Phase 3 safety and tolerability study of REMIRAL and secondary endpoints. The findings by Stephen Harrison, MD, founder of Pinnacle Clinical Research, and colleagues were published last month in natural medicine.
The MAESTRO-NAFLD-1 trial is a Phase 3 trial designed to evaluate the safety and efficacy of the investigational therapy resmetirom in adults with NAFLD, including patients with NASH. The primary endpoint of the trial is the occurrence of treatment-emergent adverse events (TEAEs) over 52 weeks. Secondary endpoints identified include reductions in low-density lipoprotein-C (LDL-C), apolipoprotein B (apoB), triglycerides, liver fat, and liver stiffness to better characterize the perceived clinical benefit.
NAFLD is a liver disease commonly seen in patients with obesity, type 2 diabetes, and dyslipidemia. It is characterized by fat accumulation in the liver and may progress to the more severe form of NASH, which is associated with liver inflammation and fibrosis. Currently, there are no approved treatments for NASH.
The FDA has granted priority review to resmetirom, and the manufacturer, Madrigal Pharmaceuticals, has submitted an NDA seeking accelerated approval. The FDA has set March 14, 2024, as the PDUFA date when a decision will be made on the drug. Resmetirom is an oral, once-daily, liver-targeted thyroid hormone receptor-beta selective agonist being developed as a potential treatment for NASH. In a phase 2 trial, patients with NASH who received remerol experienced greater reductions in liver fat compared with placebo.
related: FDA sets review date for Resmetirom to treat NASH patients
The MAESTRO-NAFLD-1 trial was conducted at 80 sites in the United States from December 16, 2019, to December 13, 2021. A total of 1,988 patients were screened, of whom 1,143 were randomly assigned to participate in the trial. Of these, 972 patients were included in the three double-blind groups and 171 patients were included in the open-label group.
The safety population included 969 patients in the double-blind group and 171 patients in the open-label treatment group. Patients in the double-blind group were randomly assigned to different doses (100 mg or 80 mg) of Remesirol or placebo, while patients in the open-label group received 100 mg of Remesirol.
The study found that remerol was safe and well tolerated by patients, although treatment-emergent adverse events (TEAEs) such as diarrhea and nausea were more common in the remerol group compared with the placebo group, particularly in the first 12 days of treatment. week. The incidence of TEAEs was similar in the Remelon and placebo groups, with most TEAEs being mild or moderate in severity. However, the rate of discontinuation due to TEAEs was slightly higher in the remerol group compared with the placebo group.
Key secondary endpoints showed favorable effects of Remelon on atherogenic lipid levels, liver fat and liver stiffness. Resmetirom treatment significantly reduced “bad” LDL cholesterol, apoB, and triglyceride levels compared with placebo. It also resulted in a reduction in liver fat at weeks 16 and 52 as measured by magnetic resonance imaging-proton density fat fraction and FibroScan-controlled attenuation parameters. Liver stiffness also improved in some patients.
The study also found that patients who combined weight loss with remelon treatment or were exposed to high doses of remelon had greater reductions in liver fat.
Harrison and colleagues reported that there was no significant difference in the mean change from baseline in liver stiffness measurements between resmetirom and placebo at week 52, but response analysis showed that a higher proportion of patients in the resmetirom group achieved Some lowering of standards. Resmelon treatment also improved markers of liver injury, particularly in patients with elevated baseline alanine aminotransferase levels.
Overall, the results of this phase 3 trial suggest that remerol may be a promising treatment option for non-alcoholic fatty liver disease given the encouraging safety and tolerability results. It has favorable effects on atherogenic lipid levels, liver fat, and liver stiffness. These findings suggest that remerol may be a potential treatment option for NASH and provide additional clinical evidence for FDA approval.