This is – in the truest sense of the word – a growing problem: more and more people in industrialized countries are developing fatty liver disease. According to the German Liver Foundation, non-alcoholic fatty liver disease is now the most common liver disease in Germany. It is usually caused by an imbalance between calorie intake and expenditure, which leads to excessive fat storage in the liver. The excess energy is stored there as a reserve for bad times.
However, this fat storage has consequences: inflammation and fibrosis of the liver can occur. For this so-called metabolic dysfunction-associated steatohepatitis (MASH) with liver fibrosis, a specific drug has now been approved for the first time.
The European Medicines Agency (EMA) approved the active ingredient resmetir for the European market in August. It is now also available in Germany.
Mechanism of action: increased fat metabolism in the liver
Resmetir binds to the thyroid receptor THR-b (THR-β) in the liver, thereby mimicking the state of increased thyroid function. This accelerates fat metabolism, breaks down triglycerides, and reduces inflammation and fibrosis.
"For sufferers, this drug is a real blessing, because for the first time we have a specific therapy that acts directly in the liver and can interrupt or at least alleviate this vicious cycle of damage, inflammation and fibrosis," explains Frank Take, director of the Clinic for Hepatology and Gastroenterology at the Charite Hospital in Berlin, to the health magazine "Visite", a public service broadcaster of NDR.
Study confirms reduction in MASH and fibrosis
Take also participated in the multinational phase III clinical trial, MAESTRO-NASH, which was pivotal to the drug's approval. The study enrolled 966 adults with steatohepatitis associated with metabolic dysfunction and varying stages of liver fibrosis. They received 80 mg of resmetiron, 100 mg of resmetiron, or placebo for 52 weeks.
The results showed that after twelve months, about 30 percent of patients who received 100 milligrams and about 26 percent of those who received about 80 milligrams of the drug had complete resolution of MASH. In the placebo group, the result was only about ten percent. In addition, fibrosis improved by at least one stage in about 26 and 24 percent of patients who received the new drug, respectively.
"What is particularly significant is that with this drug, even damage that has already occurred and is not yet too severe – i.e. the middle stages of fibrosis – can be reversed," says Rainer Günter, head of the department of hepatology at the University Hospital of Schleswig-Holstein in Kiel.
The results contributed to the EMA's decision to approve the drug in Europe as a treatment in combination with diet and exercise for MASH with moderate to advanced liver fibrosis (stages F2 to F3). However, the approval was granted under specific conditions: further evidence of the drug's effectiveness is awaited, and the EMA will assess new data at least once a year. This is because key clinical outcomes are still lacking – primarily whether the drug reduces mortality or the number of liver transplants needed. This is being investigated in the ongoing MAESTRO-NASH OUTCOMES study.
Side effects: diarrhea, nausea, and itching
In addition to its positive effects on the liver, the drug has been shown to further reduce blood fats, such as LDL cholesterol. However, resmetir also has side effects: nausea and diarrhea are very common, and itching is also common.
The current guidelines of the German Society for Gastroenterology, Digestive and Metabolic Diseases (DGVS) from 2022 do not yet list this drug as a treatment option. However, a draft guideline amendment is already available for consultation. At the same time, the Federal Joint Committee (G-BA) is conducting a benefit assessment process for this drug.
Important basic therapy: Weight loss and exercise
Until now, there has been no specific cure for MASH in Europe. The basis of therapy remains lifestyle changes: weight loss, physical activity, reduced alcohol intake and, if necessary, medications for concomitant diseases such as diabetes, fat metabolism disorders and obesity.
The German Society for Gastroenterology, Digestive and Metabolic Diseases recommends that obese patients reduce their body weight by at least five percent during MASH.
If fibrosis is already present, a ten percent weight loss is recommended. At least three hours of aerobic exercise per week is also advised. These measures lead to significant improvement in many cases and should be continued even if drug therapy is initiated.
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