Madrigal Pharmaceuticals' Rezdiffra (resmetirom, THR-β agonist) becomes the first US FDA approved drug for the treatment of NASH (MASH)

Madrigal Pharmaceuticals' Rezdiffra (resmetirom, THR-β agonist) becomes the first US FDA approved drug for the treatment of NASH (MASH) 

 

US FDA have granted accelerated approval for Rezdiffra in conjunction with diet and exercise for the treatment of adults with noncirrhotic NASH with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis). 

 

Approval is based on Phase 3 MAESTRO-NASH trial that evaluated 80 or 100 mg of MGL-3196 vs. Placebo in pts. with NASH and Fibrosis  

 

Primary endpoints:  

• NASH resolution (including a reduction in the nonalcoholic fatty liver disease [NAFLD] activity score by ≥2 points) with no worsening of fibrosis An improvement in fibrosis by at least one stage with no worsening of the NAFLD activity score 

 

Results published in NEJM showed that NASH resolution with no worsening of fibrosis was achieved in 25.9% of the pts. in the 80-mg group and 29.9% of those in the 100-mg group vs. 9.7% of those in the placebo group  

 

Rezdiffra is expected to be available to patients in the U.S. in April and will be distributed through a limited specialty pharmacy network.  

Focus on 315,000 U.S. Patients seen by ~14K target specialists 

• Comes at an annual WAC price of $47,400.  
• Co-pay support: $10 co-pays for Commercial patients 
• Patient Assistance Program also available for pts. with no insurance or no coverage for Rezdiffra 

 

MAESTRO-NASH remains ongoing as an outcomes study designed to generate confirmatory data that, if positive, will help verify clinical benefit and may support full approval 

 

A second ongoing outcomes trial (MAESTRO-NASH OUTCOMES) is evaluating progression to liver decompensation events in patients with well-compensated NASH cirrhosis treated with Rezdiffra vs. placebo.

IMFINZI (durvalumab) plus bevacizumab met primary endpoint for progression-free survival in liver cancer eligible for embolization in EMERALD-1 Phase III trial

Results from the EMERALD-1 Phase III trial have showcased positive high-level outcomes for AstraZeneca's IMFINZI (durvalumab) when combined with transarterial chemoembolization (TACE) and bevacizumab. 

This combination exhibited a statistically significant and clinically meaningful improvement in the progression-free survival (PFS) primary endpoint compared to TACE alone in patients with hepatocellular carcinoma (HCC) eligible for embolization.

The trial is ongoing, focusing on the secondary endpoint of overall survival (OS).

Hepatocellular carcinoma is the most prevalent form of liver cancer, ranking as the third-leading cause of cancer-related deaths, with approximately 900,000 new cases diagnosed annually worldwide. 

About 20-30% of patients are suitable for embolization, a procedure that restricts blood supply to the tumor while allowing the delivery of chemotherapy or radiation therapy directly to the liver. Despite being the standard of care, most patients undergoing embolization face rapid disease progression or recurrence.

Dr. Riccardo Lencioni, the principal investigator in the trial, emphasized that patients eligible for embolization often experience high rates of progression or recurrence without the opportunity for early intervention using effective systemic therapy.

The results for durvalumab plus bevacizumab suggest a potential shift in treating this challenging disease, demonstrating, for the first time, that adding an immunotherapy combination to TACE significantly enhances progression-free survival.

Susan Galbraith, Executive Vice President, Oncology R&D at AstraZeneca, expressed optimism about the potential of IMFINZI-based treatment in EMERALD-1, anticipating a groundbreaking application of immunotherapy in earlier stages of liver cancer. 

The company looks forward to discussing these findings with regulatory authorities and monitoring the maturation of survival data over time to bring this innovative treatment option to patients.

The safety profiles for IMFINZI and TACE plus bevacizumab were consistent with the known profiles of each medicine, and there were no new safety findings. The detailed data will be presented at an upcoming medical meeting and shared with regulatory authorities.

AstraZeneca is actively engaged in a comprehensive clinical development program to further evaluate IMFINZI across various gastrointestinal cancer settings. 

This includes combinations with bevacizumab in adjuvant HCC (EMERALD-2) and with IMJUDO (tremelimumab-actl), lenvatinib, and TACE in embolization-eligible HCC (EMERALD-3).