F.D.A. Early approval granted Resmetilom (Rezdiffra) is currently used as a first-line treatment for adults with non-cirrhotic non-alcoholic steatohepatitis (NASH), also known as metabolic dysfunction-associated steatohepatitis (MASH).
Resmetilom, a once-daily oral formulation, is a liver-directed thyroid hormone receptor (THR)-β selective agonist designed to target the primary underlying cause of NASH. The drug is specifically indicated for NASH patients with moderate to advanced liver fibrosis, corresponding to fibrosis stages F2 to F3, and should be used in conjunction with diet and exercise, the agency said.
“Until now, NASH patients with significant liver scarring lacked drugs that could directly address liver damage,” Dr. Nikolai Nikolov of the FDA’s Center for Drug Evaluation and Research said in a statement. “With today’s approval of RezdiFla, for the first time these patients will be offered a treatment option in addition to diet and exercise.”
As a result of the progression of nonalcoholic fatty liver disease (NAFLD), NASH can lead to liver fibrosis and dysfunction, increasing the risk of transplantation and hepatocellular carcinoma. This condition is often associated with high blood pressure and diabetes.
According to some estimates, more than 6 million Americans have stage F2 to F3 fibrosis NASH, and that number is expected to further increase in the coming years.
Results from the ongoing Phase 3 MAESTRO-NASH trial support approval, reporting that 25.9% of those receiving resmetirom 80 mg and 29.9% of those receiving 100 mg had resolution of NASH without worsening of fibrosis. His 9.7% of patients who received a placebo (P<0.001 for both comparisons with placebo).
Improvement in fibrosis by at least one grade without worsening of NAFLD activity score was achieved in 24.2%, 25.9%, and 14.2%, respectively (P<0.001 for both comparisons with placebo).
The study included only patients with liver biopsies showing inflammation due to NASH with moderate or advanced liver scarring; Prescription information The drug company Madrigal Pharmaceuticals noted that it does not include a biopsy requirement for diagnosis.
“The approval of the first treatment for NASH is a true game-changer for healthcare providers, the research community and, most importantly, patients living with this serious liver disease.” said Dr. Stephen Harrison, a researcher at Pinnacle Clinical Research in SunSun. Antonio, press release From Madrigal. “Based on the robust efficacy and safety data from two large Phase III MAESTRO studies, I believe Rezdiffra can become a cornerstone therapy for patients with NASH with moderate to progressive liver fibrosis. I am.”
As a condition of accelerated approval, Madrigal Pharmaceuticals will be required to conduct post-marketing studies to test and describe the drug’s clinical benefits in this patient population.
The study “will determine whether the positive results observed in the MAESTRO study translate into a lower risk of progression to cirrhosis, liver failure, need for liver transplantation, and early death,” Harrison said. he said.
In trials, the most common side effects of resmetilom included diarrhea, nausea, pruritus, abdominal pain, vomiting, constipation, and dizziness. Diarrhea and nausea usually began early in treatment and were mild to moderate in severity.
The FDA stated that resmetilom should not be used in patients with decompensated cirrhosis and should be discontinued if patients develop signs or symptoms of worsening liver function. Resmetirom should not be taken at the same time as certain other drugs, especially cholesterol-lowering drugs.
Resmetilom tablets are available in three doses: 60 mg, 80 mg, and 100 mg, but the recommended dose is based on the patient’s weight. 100 mg once daily for patients weighing 100 kg (220 lb) or more, or 80 lb or more. If you are under that weight, then -mg once a day.
Madrigal said resmetilom is expected to launch in the U.S. in April and will be distributed through a limited network of specialty pharmacies.
