Madrigal Pharmaceuticals received FDA approval for Resmetra.
The United States Food and Drug Administration has granted approval to Resmetra (teramisrim) for managing adults with noncirrhotic non-alcoholic steatohepatitis (NASH) with moderate to advanced liver scarring (fibrosis), alongside dietary adjustments and physical activity.
NASH develops as a consequence of the advancement of nonalcoholic fatty liver ailment wherein liver inflammation over time can result in liver scarring and liver malfunction. NASH is frequently correlated with other medical conditions like hypertension and type 2 diabetes.
Approximately 6-8 million individuals in the United States are estimated to suffer from NASH with moderate to advanced liver scarring, a figure expected to rise. Resmetra is a partial activator of a thyroid hormone receptor; its activation in the liver reduces liver fat accumulation.
The effectiveness and safety of Resmetra were assessed based on an evaluation of a surrogate endpoint at month 12 in a 54-month, randomized, double-blind placebo-controlled trial. This surrogate endpoint measured the extent of liver inflammation and scarring. A post-approval study is mandated for the sponsor to verify and elucidate Resmetra’s clinical advantages, which will be accomplished by completing the same 54-month study that is presently ongoing. Participants required a liver biopsy demonstrating inflammation due to NASH with moderate or advanced liver scarring to enroll in the trial. In the study, 888 subjects were randomly assigned to receive either placebo (294 subjects), 80 milligrams of Resmetra (298 subjects), or 100 milligrams of Resmetra (296 subjects) once daily, in addition to standard NASH care, including counseling for a healthy diet and exercise.
After 12 months, liver biopsies revealed that a higher proportion of subjects treated with Resmetra achieved NASH resolution or a reduction in liver scarring compared to those receiving placebo. Approximately 26% to 27% of subjects receiving 80 milligrams of Resmetra and 24% to 36% of those receiving 100 milligrams experienced NASH resolution and no deterioration in liver scarring, in contrast to 9% to 13% of those receiving placebo and lifestyle counseling. The variation in responses reflects differences in pathologists' interpretations. Additionally, approximately 23% of subjects receiving 80 milligrams of Resmetra and 24% to 28% of those receiving 100 milligrams experienced an improvement in liver scarring and no worsening of NASH, compared to 13% to 15% of those receiving placebo, depending on pathologists' interpretations. The demonstration of these changes in a proportion of patients after just one year of treatment is noteworthy, given that the disease typically progresses slowly, with the majority of patients taking years or even decades to show progression.
Common adverse effects of Resmetra included diarrhea and nausea. Resmetra carries specific warnings and precautions, such as drug-induced liver toxicity and gallbladder-related adverse effects.
The use of Resmetra should be avoided in patients with decompensated cirrhosis. Patients should discontinue Resmetra use if they experience signs or symptoms of worsening liver function while on treatment.
Concomitant use of Resmetra with certain other medications, particularly statins for cholesterol reduction, may lead to potentially significant drug interactions. Healthcare providers should consult the complete prescribing information for additional details on these potentially significant drug interactions with Resmetra, as well as recommended dosage adjustments and administration modifications.
The FDA granted approval to Resmetra under the accelerated approval pathway, which permits earlier approval of drugs addressing serious conditions and fulfilling unmet medical needs, based on a surrogate or intermediate clinical endpoint likely to predict clinical benefit. The aforementioned 54-month study, which is ongoing, will evaluate clinical benefits after 54 months of Resmetra treatment.
Resmetra received Breakthrough Therapy, Fast Track, and Priority Review designations for this indication.