According to the phase III MAESTRO-NASH trial, the investigational agent resmetirom has demonstrated positive results in treating nonalcoholic steatohepatitis (NASH). The study found that the drug resolved liver biopsy findings in NASH more often than the placebo. While only 10% of the placebo patients achieved resolution of inflammation, ballooning, and disease activity, the rate was 26% among people treated with the 80-mg dose of resmetirom and 30% with the 100-mg dose of resmetirom.
In the co-primary endpoint of the trial, 14% of patients on placebo had liver fibrosis improve by at least one stage without a worsening of non-alcoholic fatty liver disease activity score (NAS) compared with 24% of patients taking 80 mg daily of resmetirom and 26% on the 100 mg dose of the agent. The results show that resmetirom is the first treatment to achieve meaningful effects on both primary liver endpoints and is reasonably likely to produce clinical benefit with these NASH patients, according to Stephen Harrison, MD, of Pinnacle Clinical Research in San Antonio.
Resmetirom demonstrates an excellent safety profile
The study reported an “excellent” safety profile for resmetirom, with the most common adverse events being gastrointestinal (GI)-related. They were mild to moderate and tended to occur early in the course of treatment. The study also reported that study discontinuations in the 100-mg arm were increased relative to placebo only during the first few weeks of treatment and were similar in all treatment groups for the remaining period of the first 52 weeks of treatment.
Importantly, there were no adjudicated cases of drug-induced liver injury in the MAESTRO-NASH trial, an issue that has caused concern with other drugs investigated for NASH, a severe form of fatty liver disease for which no approved treatment exists.
To be eligible for the phase III trial, which was presented as a plenary late-breaker, patients were required to have been diagnosed with at least three metabolic risk factors, to have had a biopsy result indicating at least a NAS 4 score, to be in fibrosis stage F1B, F2, or F3, and to have had at least 8% hepatic fat measured by MRI scans.
The research team reported that patients treated with resmetirom achieved significant reductions relative to placebo in key noninvasive tests, including MRI-proton density fat fraction. At 52 weeks, fat reduction of 42% was observed with the 80-mg dose, 51% among patients treated with 100-mg resmetirom, and 10% among placebo patients.
The results of the MAESTRO-NASH trial demonstrate the efficacy of resmetirom in treating NASH, with the drug outperforming the placebo in resolving liver biopsy findings. The study also reports an excellent safety profile for the drug, with no adjudicated cases of drug-induced liver injury. While the study acknowledges the limitation of the lack of clinical outcomes data to correlate with the biopsy data, the MAESTRO-NASH trial will continue for 54 months to accrue and evaluate clinical outcomes. Resmetirom is a promising drug in treating NASH, with both 80- and 100-mg doses being effective, giving patients and their doctors options for treatment.