CONSHOHOCKEN, PA — Madrigal Pharmaceuticals Inc. (NASDAQ: MDGL) reported that its liver disease drug Rezdiffra improved measures of liver damage across patients carrying common genetic risk variants for metabolic dysfunction-associated steatohepatitis, potentially broadening confidence in the treatment’s effectiveness across genetically diverse patient populations.
The findings come from a prespecified secondary analysis of the Phase 3 MAESTRO-NASH trial, published in the Journal of Hepatology, examining whether genetic differences associated with disease progression affected patients’ responses to Rezdiffra, also known as resmetirom.
Researchers evaluated treatment outcomes among patients carrying variants in five genes associated with MASH progression: PNPLA3, HSD17B13, TM6SF2, MTARC1 and MBOAT7.
Across the genetic subgroups examined, Rezdiffra treatment was associated with improvements in liver fibrosis, resolution of MASH, reductions in liver fat measured by magnetic resonance imaging-proton density fat fraction (MRI-PDFF), and changes in disease-related biomarkers.
The findings suggest that the genetic variants evaluated did not prevent patients from benefiting from treatment, although the analysis was secondary to the trial’s primary objectives.
MASH is a form of fatty liver disease characterized by liver inflammation and damage. Its progression is influenced by metabolic conditions and inherited genetic factors, which can contribute to fibrosis, cirrhosis and liver cancer.
Determining whether genetic differences influence treatment effectiveness has implications for how physicians select therapies as additional MASH treatments are developed.
Naga Chalasani, a professor of gastroenterology and hepatology at Indiana University School of Medicine and the study’s lead author, said emerging research suggests that genetic variation could affect responses to some MASH therapies.
“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,” Chalasani said.
The PNPLA3 variant is among the genetic factors associated with MASH progression, making its potential influence on treatment response a focus of clinical research.
The secondary analysis found improvements in liver histology and biomarkers across the genetic subgroups evaluated, supporting further investigation into how inherited risk factors affect treatment outcomes.
Madrigal Chief Medical Officer David Soergel said the results also inform the company’s development strategy, which includes investigating therapies directed at specific genetic drivers of liver disease.
“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,” Soergel said.
The analysis adds genetic subgroup findings to the clinical evidence from MAESTRO-NASH, rather than representing a separate trial or a new regulatory approval.
The results support the possibility that Rezdiffra’s therapeutic effects extend across several common MASH-associated genetic variants, while the findings remain specific to the patient subgroups and outcomes examined in the analysis.
Support the local news that supports Chester County. MyChesCo delivers reliable, fact-based reporting and essential community resources—free for everyone. If you value that, click here to become a patron today.