Navigating NASH Treatment – Future Therapies

Nonalcoholic fatty liver disease (NAFLD) encompasses conditions characterised by excess fat in the liver which are unrelated to alcohol consumption. The prevalence of NAFLD amongst adults worldwide is estimated to be as high as 32.4%. In Europe, prevalence rates of 26.9 to 30.9% have been reported, with the condition occurring more frequently in men than in women.

Nonalcoholic steatohepatitis (NASH) is a progressive liver disease and the most severe form of NAFLD. It leads to liver inflammation, swelling, damage and scarring, and is typically diagnosed through a liver biopsy. It is becoming an increasing cause of liver transplantation. NASH affects those with conditions like obesity, diabetes, high cholesterol and occurs typically between the ages of 40 and 60 years. The traditional treatment approach involves weight loss and increased physical activity, which can help to reduce fat, inflammation, and scarring in the liver. Currently, there are no approved drug therapies for NASH in the EU or UK.

A number of drugs are being investigated for use in the treatment of NASH. Recently, the New England Journal of Medicine highlighted the efficacy of resmetirom in patients with NASH, who also have signs of liver scarring. Resmetirom is a thyroid hormone receptor-beta agonist from Madrigal Pharmaceuticals. The Phase 3 trial, MAESTRO-NASH, showed positive primary and secondary endpoint results with an improvement in NASH, no worsening of scarring, and a reduction in cholesterol levels in patients taking resmetirom.

While resmetirom leads the way, NASH treatment developments continue. Other drugs under investigation include GLP-1 agonists, such as semaglutide and tirzepatide, azemiglitazone, a thiazolidinedione-like molecule, and belapectin, an IV galectin inhibitor.

Given the varying mechanisms of action of the upcoming products, combination therapy could possibly be a consideration for physicians in treatment. Another consideration is the diagnosis of NASH. Although trial efficacy has been modest and liver biopsy remains a key clinical trial inclusion criterion, ongoing research on non-invasive diagnostic criteria may reshape the approach to NASH treatment.

As the pharmaceutical market adapts to these novel therapies, the medical community awaits further insights and non-invasive diagnostic criteria to optimise the treatment paradigm and manage the associated costs effectively.

For more information on NASH and future treatment developments, click here to read this issue’s clinical bulletin.