Madrigal Announces Publication in the Journal of Hepatology Demonstrating Consistent Rezdiffra Efficacy Across Common MASH Genetic Risk Variants
Key Highlights
- ➤Rezdiffra improved MASH resolution, fibrosis and liver fat across five genetic risk variants
- ➤738-patient analysis found no meaningful genotype-based difference across major efficacy endpoints
- ➤Rezdiffra responses remained consistent after accounting for sex and Hispanic ethnicity
- ➤PNPLA3 subgroup MASH resolution reached 38.4% versus 12.9% for placebo in low-risk genotypes
- ➤Madrigal added PNPLA3-targeting siRNA MGL-0795 to its pipeline for potential combination therapy
Expert Statements
Naga Chalasani, David W. Crabb Professor of Gastroenterology and Hepatology at Indiana University School of Medicine and lead author of the study
“Understanding how common MASH risk alleles may influence a patient’s response to treatment will be increasingly important as the treatment landscape and number of diagnosed patients continue to evolve. For example, there is emerging evidence suggesting that response to various therapies could differ in individuals with MASH carrying the PNPLA3 allele, and it will be important to perform similar analyses for other approved and investigational MASH therapies moving forward”
Naga Chalasani, David W. Crabb Professor of Gastroenterology and Hepatology at Indiana University School of Medicine and lead author of the study
“It is encouraging to see that Rezdiffra demonstrated consistent effects on liver histology and biomarkers across the genetic risk subgroups evaluated, supporting broad applicability across patients with this serious liver disease.”
David Soergel, Chief Medical Officer of Madrigal
“MASH is a complex, heterogeneous disease driven by both metabolic and genetic factors”
David Soergel, Chief Medical Officer of Madrigal
“These data reinforce that Rezdiffra provides broad benefit across patients with MASH, including those with the most common genetic risk variants that may put them at higher risk of disease progression, cirrhosis and liver cancer, strengthening its position as a foundation of MASH treatment. These results also support our pipeline strategy of developing precision approaches targeting well-defined genetic drivers of disease that may complement Rezdiffra in specific patient populations.”
* Secondary analysis of the Phase 3 MAESTRO-NASH trial demonstrated Rezdiffra improved histology and MRI-PDFF across common genetic variants associated with MASH progression CONSHOHOCKEN, Pa., Oct. 06, 2026 (GLOBE NEWSWIRE) -- Madrigal Pharmaceuticals, Inc. (NASDAQ: MDGL), a biopharmaceutical company focused on delivering novel therapeutics for metabolic dysfunction-associated steatohepatitis (MASH), today announced the publication of a pre-specified secondary analysis from the Phase 3 MAESTRO-NASH trial in the Journal of Hepatology evaluating whether common genetic risk variants associated with MASH altered patient response to Rezdiffra(®) (resmetirom).
The analysis demonstrated that treatment with Rezdiffra resulted in fibrosis improvement, MASH resolution and liver fat and biomarker reductions across patients with several well-established genetic variants associated with MASH progression, including PNPLA3, HSD17B13, TM6SF2, MTARC1 and MBOAT7. The findings suggest that Rezdiffra may have a therapeutic effect regardless of genetic risk factors that contribute to more severe disease.
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