Overview of MAESTRO-NASH Trial
The Phase 3 MAESTRO-NASH trial of Resmetirom, published in the New England Journal of Medicine, has provided fresh hope for patients suffering from Nonalcoholic Steatohepatitis (NASH) with significant liver fibrosis. NASH is a leading cause of liver-related mortality and is increasingly becoming a burden on healthcare systems worldwide. This illness is rapidly becoming the leading cause of liver transplantation in the U.S. and currently lacks approved treatments. Resmetirom, a once-daily oral liver-directed THR Î² agonist, shows potential to fill this gap.
Resmetirom's Breakthrough Therapy Designation
Resmetirom has received a Breakthrough Therapy designation from the Food and Drug Administration (FDA). It is currently under review to become the first approved medicine to treat patients with NASH with liver fibrosis. This designation is a significant development, as it fast-tracks the review process for drugs that show substantial potential in treating a serious or life-threatening disease. Resmetirom's liver-directed mode of action aims to target the fundamental causes of NASH, making it a potential game-changer in NASH treatment.
Pivotal Results from the MAESTRO-NASH Trial
During the trial, patients with biopsy-confirmed NASH and a fibrosis stage of F1B, F2, or F3 were randomly assigned to receive either 80 mg or 100 mg of resmetirom or placebo once daily. The primary endpoints at week 52 were NASH resolution and fibrosis improvement. In the 80 mg resmetirom group, 25.9% of patients achieved NASH resolution with no worsening of fibrosis, and 29.9% in the 100 mg group. This compared favourably to a 9.7% resolution rate in the placebo group. Moreover, fibrosis improvement by at least one stage with no worsening of the NAFLD activity score was achieved in 24.2% of the patients in the 80 mg resmetirom group and 25.9% in the 100 mg group, compared to 14.2% in the placebo group. These results reinforce the potential of resmetirom in treating NASH.
Additional Benefits and Side Effects of Resmetirom
Resmetirom also demonstrated a significant change in low-density lipoprotein cholesterol levels from baseline to week 24 compared to the placebo group. Additionally, patients receiving resmetirom experienced reductions in levels of a broad range of atherogenic lipids and lipoproteins, including LDL cholesterol, non-high-density lipoprotein cholesterol, triglycerides, apolipoprotein B, and lipoprotein(a). However, diarrhea and nausea were more frequently reported with resmetirom than with placebo, and the incidence of serious adverse events was similar across trial groups. While more patients in the 100-mg group discontinued the trial due to adverse events, it is noteworthy that most adverse events were mild to moderate in severity.
The ongoing MAESTRO-NASH trial has indeed provided promising evidence that resmetirom could be a potential treatment option for NASH with liver fibrosis. The trial's significant findings offer hope for patients suffering from this condition. However, as with any potential treatment, it is necessary to weigh the benefits against the possible side effects. As always, patients should discuss potential treatment options with their healthcare provider.