Resmetirom Shows Promise for Fatty Liver in Early Analysis

Laird Harrison

July 01, 2021

The experimental oral drug resmetirom appears to reverse biomarkers for nonalcoholic steatohepatitis (NASH), researchers report.

Patients taking the drug in an open-label arm of the phase 3 Maestro-NAFLD-1 trial showed a rapid reduction in hepatic fat, fibrosis, low-density lipoproteins, and other biomarkers for inflammation and liver injury.

"We see a drug that is safe and appears to be well tolerated, with some drops in noninvasive tests that are consistent with overall improvement in liver health," said Stephen Harrison, MD, at a press conference at the International Liver Congress (ILC) 2021.

The results bear out the phase 2 findings, but they are only preliminary, he cautioned.

"I would say that the study is limited in that there is no placebo arm here; this is open-label," Harrison said.

Researchers are working to confirm these results with biopsies and also in comparison to placebo groups in another arm of the Maestro-NAFLD-1 trial and in the separate Maestro-NASH trial, he said.

Currently, no drugs have been approved by the US Food and Drug Administration to treat NASH, an increasingly prevalent disease.

Madrigal Pharmaceuticals designed resmetirom to reduce fat in the liver by targeting the pathway by which thyroid hormone helps control lipid metabolism. It has touted the drug, a small molecule, as more selective than previous compounds tested for this purpose. The drug appeared successful in safely reducing biomarkers for NASH in a phase 2 trial.

In Maestro-NAFLD-1, the researchers evenly divided 1200 patients into four groups, three blinded and one open label. Of the three blinded groups, one was assigned to a placebo, one to resmetirom 100 mg, and one to resmetirom 80 mg. The open-label group is also taking resmetirom 100 mg.

At the ILC, Harrison presented the preliminary results of 115 patients from the open-label arm of the study who had completed 52 weeks of treatment.

Patients were predominantly women (71%). At baseline, their mean age was 55.7 years, and the mean body mass index was 36.2. Of the patients presented, 41% had diabetes, 64% had hypertension, 70% had dyslipidemia, and 41% had hypothyroidism.

Other notable baseline characteristics included the following: mean atherosclerotic cardiovascular disease score, 11.1%; mean FibroScan result, 7.4 kPa; mean controlled attenuation parameter (CAP), 341 dB/m; and mean liver fatness by MRI proton-density fat fraction (MRI-PDFF), 18%.

After 52 weeks, the patients' CAP scores improved by 45.2%, and their liver fatness, measured by MRI-PDFF, improved by 53.4%. Both were statistically significant (P < .0001).

Liver stiffness dropped by 11.9%, as measured by MR enterography (which was significant at P = .01), and by 26%, as measured by FibroScan (which was significant at P = .0006).

Liver enzyme levels declined in those patients who had mildly or moderately elevated levels at baseline.

Markers of cardiovascular disease, including low-density lipoprotein cholesterol, apolipoprotein B, triglycerides, and blood pressure, all declined.

Adverse events included increased stool frequency. COVID-19 was the most severe adverse event, but it was not deemed to be related to the treatment. Only one patient withdrew because of an adverse event. There were no central thyroid axis changes.

In addition to providing encouraging signs for resmetirom, the study showed the potential for noninvasive tests to diagnose and monitor NASH.

"I think it's an exciting trial, with some exciting data that really builds on the utilization of these noninvasive tests for monitoring disease activity," Harrison told Medscape Medical News.

The overall results are encouraging, agreed Mohammed Medhat, a lecturer in tropical medicine and gastroenterology at Assiut University Hospitals, in Assiut, Egypt.

"This is a very promising drug," he told Medscape Medical News.

Other potential candidates to treat patients with NASH are pioglitazone and vitamin E. They are also being tested in randomized clinical trials, Medhat said.

The study was funded by Madrigal Pharmaceuticals. Medhat has disclosed no relevant financial relationships. Harrison has received grant funding from Merck and is a consultant to Madrigal Pharmaceuticals and multiple other companies involved in liver health.

International Liver Congress (ILC) 2021: Abstract GS-2563. Presented June 25, 2021.

Laird Harrison writes about science, health, and culture. His work has appeared in magazines, newspapers, and online publications. He is at work on a novel about alternate realities in physics. Harrison teaches writing at the Writers Grotto. Visit him at or follow him on Twitter: @LairdH.

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