The US Food and Drug Administration (FDA) has approved Rezdiffra™ (resmetirom), the first medication for treating patients with nonalcoholic steatohepatitis (NASH) with moderate to advanced liver scarring. NASH is a type of nonalcoholic fatty liver disease (NAFLD), which includes conditions characterized by fat buildup in the liver unrelated to chronic alcohol use.
NASH and NAFLD’s recent reclassification to metabolic dysfunction-associated steatohepatitis (MASH) and metabolic dysfunction-associated steatotic liver disease (MASLD) reflects the evolving understanding of these conditions. The FDA approval and clinical trial results referenced here use the original terminology, as will this blog.
Understanding NASH: A Hidden Danger
NASH is a progressive disease. It begins as fatty liver disease and can worsen with the development of inflammation and scarring. Over time, this scarring, called fibrosis, can worsen, leading to cirrhosis, which may require a liver transplant. Wajahat Mehal, director of the Yale Metabolic Health & Weight Loss Program, notes the connection between obesity and liver damage. “Particularly with chronic overnutrition, the body stores fat in many places, including the liver,” he said. “Most people with obesity or overweight are going to have high levels of fat in their liver, and that means they have NAFLD. But, over time, about a quarter of people with NAFLD will start to experience liver damage. That’s when NAFLD transitions to NASH.”
An estimated 6 to 8 million Americans have NASH with moderate to advanced liver scarring. While early stages of NAFLD and NASH can be reversed through weight loss, scarring from advanced NASH may not be reversible. The disease often progresses without symptoms, making diagnosis difficult until significant liver damage has occurred. NASH can often be diagnosed using blood tests and imaging, with only 10% of cases requiring a liver biopsy.
Rezdiffra: A New Treatment Option
Rezdiffra was developed by Madrigal Pharmaceuticals. It is administered as a daily pill and works by activating a thyroid hormone receptor. Clinical trials have demonstrated its ability to reduce liver fat. In a Phase III trial that compared an 80 mg dose, a 100 mg dose and a placebo, about a quarter of patients receiving the drug experienced NASH resolution with no worsening of fibrosis. The trial results were published in the New England Journal of Medicine. At the lower dose, 26% of patients saw improvement without worsening fibrosis, while the higher dose achieved results in 30% of patients. For fibrosis improvement alone, the results were similarly encouraging, with 24% and 26% of patients showing progress at the lower and higher doses, respectively.
The FDA granted Rezdiffra accelerated approval, contingent on further study results. For now, the medication is available for adults with moderate to advanced NASH who haven’t yet reached the stage of severe cirrhosis. Mehal expects insurance carriers to cover the drug and plans to prescribe it to patients who meet the criteria. However, he emphasizes that Rezdiffra should be used alongside a healthy diet and physical activity.
Side Effects and Weight Loss Considerations
Rezdiffra’s side effects include nausea and diarrhea, and there are concerns about drug-induced liver toxicity and gallbladder-related issues. Additionally, the drug may interact with other medications, such as statins used for lowering cholesterol.
Obesity remains a significant contributor to NASH, and patients can see improvement through weight loss. Anti-obesity drugs like semaglutide and tirzepatide have shown promise in managing NAFLD, but not in reversing NASH. Mehal is hopeful about ongoing trials and believes these medications may also have a place in treating NASH.
Turning the Page on Treating NASH
Rezdiffra marks a new chapter in treating liver disease. “Now that the FDA has approved a drug for NASH, pharmaceutical companies will have a better understanding of the thresholds they must meet to get future approvals,” said Mehal. “This makes them more enthusiastic about continuing drug development in this area. And there are many promising medications coming along.” This is great news for the country’s 6 to 8 million adults who could benefit from new therapies.
Did you enjoy this blog post? Check out our other blog posts as well as related topics on our Webinar page.
QPS is a GLP- and GCP-compliant contract research organization (CRO) delivering the highest grade of discovery, preclinical and clinical drug research development services. Since 1995, it has grown from a tiny bioanalysis shop to a full-service CRO with 1,100+ employees in the US, Europe and Asia. Today, QPS offers expanded pharmaceutical contract R&D services with special expertise in pharmacology, DMPK, toxicology, bioanalysis, translational medicine, cell therapy (including PBMCs, leukopaks and cell therapy products) and clinical development. An award-winning leader focused on bioanalytics and clinical trials, QPS is known for proven quality standards, technical expertise, a flexible approach to research, client satisfaction and turnkey laboratories and facilities. Through continual enhancements in capacities and resources, QPS stands tall in its commitment to delivering superior quality, skilled performance and trusted service to its valued customers. For more information, visit www.qps.com or email info@qps.com.
