Resmetirom Phase 3 Trial Published in NEJM

Madrigal Pharmaceuticals, a clinical-stage biopharmaceutical firm, has made significant strides in the development of resmetirom, a potential treatment for nonalcoholic steatohepatitis (NASH). The company has reported the successful completion of a pivotal Phase 3 trial, MAESTRO-NASH, which demonstrated the drug's effectiveness in improving fibrosis and resolving NASH, key indicators for the disease's progression. The study was published in the New England Journal of Medicine, offering a comprehensive look at the efficacy and safety profile of resmetirom.

NASH, a severe form of nonalcoholic fatty liver disease, poses a significant threat to global healthcare systems, with increasing rates of liver-related mortality. The FDA has recognized the urgency of the situation by granting resmetirom a Breakthrough Therapy designation and Priority Review, setting a target action date of March 14, 2024, for its review process.

The MAESTRO-NASH trial was a landmark study that compared resmetirom treatment to a placebo in patients with significant fibrosis, a group at high risk for cirrhosis and other severe liver conditions. The trial's design included a 52-week biopsy assessment and a 54-month outcomes study to confirm the drug's long-term benefits. Remarkably, the trial achieved both primary endpoints proposed by the FDA, indicating that resmetirom could not only halt the worsening of fibrosis but also reduce it without increasing NAFLD activity scores.

Dr. Stephen Harrison, the lead Principal Investigator of the MAESTRO studies, highlighted the significance of the publication, stating that it provides clinicians with valuable information about a medication that could soon become the first approved therapy for NASH.

The results of the 52-week biopsy portion showed promising outcomes, with approximately half of the patients treated with resmetirom showing either NASH resolution or fibrosis improvement. Furthermore, over 80% of these patients experienced either fibrosis reversal or no progression.

Dr. Becky Taub, Madrigal's Chief Medical Officer, emphasized the importance of resmetirom for patients with significant fibrosis, who are at a higher risk of developing severe liver conditions and are in need of effective treatments. The MAESTRO-NASH study also achieved multiple secondary endpoints, including significant reductions in liver enzymes and improvements in lipid profiles and fibrosis biomarkers.

Safety was a critical aspect of the trial, and the incidence of serious adverse events was comparable across treatment groups. Common transient side effects included diarrhea and nausea, which were more frequent at the start of therapy but subsided after the initial weeks.

Bill Sibold, Madrigal's CEO, expressed optimism about resmetirom's potential to become the foundational therapy for NASH with significant fibrosis, transforming care for patients who currently have no approved treatment options. The company is building on its leadership in NASH drug development with ongoing trials aimed at confirming clinical benefits and expanding the patient population eligible for treatment.

Resmetirom is a once-daily, oral, liver-directed THR-β agonist, designed to address the root causes of NASH. Madrigal is conducting multiple Phase 3 trials to assess the drug's safety and efficacy, with the MAESTRO-NASH trial being a key component of the company's submission for accelerated FDA approval.

NASH is a pressing health concern, with no FDA-approved treatments currently available. Madrigal estimates that around 1.5 million patients in the U.S. have been diagnosed with the disease, and the company plans to focus on patients under the care of liver specialists during the launch of resmetirom.

In conclusion, Madrigal Pharmaceuticals' resmetirom has shown promising results in treating NASH, a disease with a significant unmet medical need. The successful Phase 3 trial and the upcoming FDA review represent a crucial step forward in addressing this global health challenge.