Madrigal Receives Positive CHMP Opinion for Resmetirom (Rezdiffra) for MASH
Madrigal Pharmaceuticals announced that the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) issued a positive opinio...
Breakthrough Clinical Results
Madrigal Pharmaceuticals announced that the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion recommending the approval of resmetirom (Rezdiffra) for treating adults with noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH) and moderate to advanced liver fibrosis. This follows the FDA's accelerated approval in March 2024. The European Commission's decision is expected in August 2025. Resmetirom is a once-daily, oral, liver-directed THR-β agonist that targets key underlying causes of MASH. The CHMP opinion is based on positive results from the Phase 3 MAESTRO-NASH trial, which showed both fibrosis reduction and MASH resolution. If approved, resmetirom will be the first medication for MASH in the EU.
Key Highlights
- Positive CHMP opinion recommending approval of resmetirom (Rezdiffra) for MASH in the EU.
- European Commission decision expected in August 2025.
- Resmetirom is the first medication to achieve fibrosis improvement and MASH resolution in a Phase 3 trial.
- Resmetirom already approved by the FDA in March 2024.
Incidence and Prevalence
Global MASLD Burden (2021)
- Point Prevalence: 15,018.1 cases per 100,000 population (95% UI 13,756.5-16,361.4)
- Annual Incidence: 608.5 cases per 100,000 population (95% UI 598.8-617.7)
- Years Lived with Disability (YLDs): 0.5 years (95% UI 0.3-0.8)
Prevalence in Specific Populations
- Sex: Higher in men (15,731.4 cases per 100,000) than women (14,310.6 cases per 100,000)
- Age: Peaks at 45-49 years for men and 50-54 years for women
Highest Prevalence Countries (2021)
- Kuwait: 32,312.2 cases per 100,000 (95% UI 29,947.1-34,839.0)
- Egypt: 31,668.8 cases per 100,000 (95% UI 29,272.5-34,224.7)
- Qatar: 31,327.5 cases per 100,000 (95% UI 29,078.5-33,790.9)
Largest Prevalence Increases (2010-2021)
- China: 16.9% (95% UI 14.7%-18.9%)
- Sudan: 13.3% (95% UI 9.8%-16.7%)
- India: 13.2% (95% UI 12.0%-14.4%)
MASLD and Type 2 Diabetes (T2D)
In patients with T2D:
- Global pooled prevalence of MASLD: 65.33% (95% CI 62.35%-68.18%)
- Prevalence of MASH (in those with biopsy-proven MASLD): 66.44% (95% CI 56.61%-75.02%)
Important Note: While the question asks specifically about MASH, the provided abstracts primarily focus on MASLD. MASH is a subtype of MASLD characterized by inflammation and liver cell damage. The prevalence of MASH is estimated within the subset of individuals with biopsy-confirmed MASLD and T2D. More research is needed to determine the global prevalence of MASH independent of T2D.
It's also important to note that MASLD affects more than a third of the world's adult population and represents a substantial economic burden on healthcare systems.
Economic Burden
MASH/NASH Economic Burden
The economic burden of MASH (Metabolic dysfunction-associated steatohepatitis), formerly known as NASH (non-alcoholic steatohepatitis), is substantial in both the US and Europe. Several studies highlight the increasing costs associated with this condition.
GAIN Study (2018 data): This study provides real-world data on NASH-associated costs in five European countries (UK, France, Germany, Spain, and Italy) and the USA. The mean total annual per-patient cost of NASH was estimated as follows:
- Direct medical costs: €2,763
- Direct non-medical costs: €4,917
- Indirect costs: €5,509
The study noted that the USA had the highest per-patient cost, while France had the lowest. Costs increased with disease progression (fibrosis and decompensation), primarily driven by hospitalization and comorbidities. Indirect costs were mainly due to work loss.
US-based Claims Data Analysis (2023 data): Another study analyzed US claims data and stratified MASH patients by FIB-4 score (a measure of liver fibrosis). The study found that higher FIB-4 scores (indicating more severe disease) were associated with significantly higher liver-related costs. Specifically:
- Patients with indeterminate FIB-4 scores had 3.68 times higher liver-related costs than those with low FIB-4 scores.
- Patients with high FIB-4 scores had a staggering 33.73 times higher liver-related costs compared to those with low FIB-4 scores.
This study also observed increased all-cause hospitalization rates in the high FIB-4 group and higher cardiovascular-related costs in both the indeterminate and high FIB-4 groups.
General Observations:
- MASLD/NAFLD Global Burden: A meta-analysis of studies from 1990-2019 estimated the global prevalence of NAFLD/MASLD at 30% and rising. This broader context underscores the growing economic impact of liver diseases like MASH.
- Cost Drivers: Across studies, key cost drivers for MASH/NASH include hospitalization, comorbidities (like diabetes and cardiovascular disease), and indirect costs related to lost productivity.
- Future Projections: Given the rising prevalence of MASLD/NAFLD and the progressive nature of MASH, the economic burden is expected to increase further without effective interventions.
It's important to note that these studies represent snapshots in time and methodologies may vary. Continued research is needed to monitor the evolving economic impact of MASH and to evaluate the cost-effectiveness of emerging therapies.
Drug used in other indications
Resmetirom, a thyroid hormone receptor (THR) β agonist, is primarily known and FDA-approved for treating Metabolic dysfunction-associated steatohepatitis (MASH) and liver fibrosis. While the provided text focuses heavily on its use in MASH, it also mentions its potential use alongside other medications to optimize metabolic factors, suggesting possible trials or investigations in related metabolic conditions.
Specifically, the text mentions its use with:
- Glucagon-like peptide-1 (GLP-1) receptor agonists: These are commonly used to treat type 2 diabetes and have shown promise in managing MASH. Combining resmetirom with GLP-1 agonists could enhance metabolic benefits and improve liver health in patients with both conditions.
- Hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins): Statins are widely used to lower cholesterol levels and have also demonstrated some benefits in MASH. Combining resmetirom with statins could potentially improve lipid metabolism and reduce cardiovascular risk in MASH patients.
While the text doesn't explicitly mention clinical trials for resmetirom outside of MASH, its suggested use alongside these medications implies potential investigations into its efficacy in related metabolic conditions like type 2 diabetes and dyslipidemia. Further research is needed to confirm these potential applications and determine the optimal intervention models for such trials.
Potential Intervention Models for Future Trials:
- Combination therapy trials: These trials would evaluate the efficacy and safety of resmetirom in combination with other medications like GLP-1 agonists or statins in patients with MASH and other metabolic conditions.
- Dose-ranging studies: These studies would investigate the optimal dose of resmetirom for different patient populations and in combination with other therapies.
- Long-term efficacy and safety trials: These trials would assess the long-term effects of resmetirom on liver health, metabolic parameters, and cardiovascular outcomes.
- Trials in specific patient subgroups: These trials would focus on the efficacy of resmetirom in patients with specific metabolic profiles or genetic predispositions.
It's important to note that this information is based on indirect inferences from the provided text. Dedicated clinical trials are necessary to confirm the efficacy and safety of resmetirom in indications other than MASH.
