Resmetirom (Madrigal Pharmaceuticals) is a thyroid hormone receptor (THR) β-selective agonist which selectively targets receptors in the liver. The THR is involved in the regulation of metabolism, cholesterol, and triglycerides, as well as the pathological buildup of fat in the liver. The high liver specificity of resmetirom aims to avoid adverse events associated with THR activation outside the liver. There are low to undetectable traces of resmetirom in the heart, bone, and brain. Resmetirom primarily works by reducing the buildup of additional fat in the liver, which alleviates the associated inflammation caused by excess liver fat in non-alcoholic steatohepatitis (NASH) patients. Subsequently, there should be an increase in NASH resolution and ultimately a reduction in fibrosis stage as the liver begins to regenerate.
If Phase II results are replicated in Phase III studies, resmetirom will likely experience strong uptake due to its robust safety profile and encouraging efficacy data as measured by NASH resolution, fibrosis regression, and liver fat reduction. Resmetirom has a unique advantage compared to other NASH contenders as it exhibited positive effects on low-density lipoprotein cholesterol (LDL-C), suggesting possible cardiovascular (CV) benefits, which is desirable given the elevated CV risk in the NASH population. In addition, Phase II trial data revealed favorable rates of NASH resolution (27% vs 6% placebo) after 36 weeks of treatment, and it is important to note that a longer follow-up duration could yield higher rates of reduction given the lagging nature of fibrosis improvement, particularly as the reduction in liver fat was sustained throughout the trial. Despite the strong correlation observed between patients experiencing relative fat reductions of ≥30% at 12 weeks, measured by magnetic resonance imaging proton density fat fraction (MRI-PDFF), and histological biopsy data, regulators will still likely require biopsy data to make informed decisions regarding regulatory approval. However, these results can be used to educate specialists around the potential use of non-invasive tests in NASH.
LIST OF FIGURES
10 Figure 1: Datamonitor Healthcare’s drug assessment summary of resmetirom for NASH
11 Figure 2: Datamonitor Healthcare’s drug assessment summary of resmetirom for NASH
13 Figure 3: Resmetirom sales for NASH across the US and five major EU markets, by country, 2018–27
LIST OF TABLES
6 Table 1: Resmetirom drug profile
8 Table 2: Late-phase trials of resmetirom for NASH
9 Table 3: Resmetirom for NASH – SWOT analysis
Pharma Intelligence UK Limited is a company registered in England and Wales with company number 13787459 whose registered office is Suite 1, 3rd Floor, 11 - 12 St. James's Square, London, England, SW1Y 4LB. The Pharma Intelligence group is owned by Caerus Topco S.à r.l. and all copyright resides with the group.