FDA Approves Resmetirom (REZDIFFRA™) as First Treatment for NASH

Key Insights

• The FDA granted accelerated approval to resmetirom (REZDIFFRA™) on March 14, 2024, marking it as the first approved therapy for non-alcoholic steatohepatitis (NASH).
• Resmetirom is an oral, liver-targeting, once-daily THR-β-selective agonist, initially discovered at Roche Nutley, offering a novel approach to NASH treatment.
• This approval signifies a historic milestone in liver drug discovery, addressing a significant unmet need in the treatment of NASH, now also known as MASH.

The FDA has granted accelerated approval to resmetirom (REZDIFFRA™) on March 14, 2024, making it the first drug specifically indicated for the treatment of non-alcoholic steatohepatitis (NASH), now also referred to as MASH. This approval marks a significant advancement in the treatment of liver diseases, addressing a critical unmet need in the medical community.

Mechanism of Action

Resmetirom is an orally administered, liver-targeting, THR-β-selective agonist. Designed for once-daily dosing, it selectively activates the thyroid hormone receptor beta (THR-β) in the liver. This activation plays a crucial role in regulating lipid metabolism, reducing liver fat accumulation, and mitigating inflammation and fibrosis associated with NASH.

Clinical Significance

The approval of resmetirom represents a historic milestone for liver drug discovery. NASH, a severe form of non-alcoholic fatty liver disease (NAFLD), affects millions worldwide and can lead to cirrhosis, liver failure, and hepatocellular carcinoma. Currently, management strategies primarily focus on lifestyle modifications, such as diet and exercise, with limited pharmacological options available. Resmetirom offers a targeted therapeutic approach to directly address the underlying pathophysiology of NASH.

Development and Discovery

Originally discovered at Roche Nutley, resmetirom's journey to FDA approval highlights the importance of innovative drug discovery efforts. The molecule's selective action on THR-β minimizes systemic hormonal effects, enhancing its safety profile. This selectivity is crucial for avoiding potential adverse effects associated with non-selective thyroid hormone receptor agonists.

Future Implications

With the FDA's accelerated approval, resmetirom is poised to transform the treatment landscape for NASH. Ongoing studies will further evaluate its long-term efficacy and safety, potentially leading to full approval and broader clinical use. This development also paves the way for further research and development of novel therapies targeting liver diseases.