Independent AI-based qFibrosis® analysis confirmed zabopegdutide’s antifibrotic benefit in Phase 2 MASH trial, reinforcing histopathology results and supporting continued development.
Written By: Nalam Karthik, PharmD
Reviewed By: Pharmacally Editorial Team
D&D Pharmatech and HistoIndex reported that an independent AI-driven analysis (NCT06410924) of liver biopsy samples confirmed the antifibrotic effects of zabopegdutide (DD01) in patients with metabolic dysfunction-associated steatohepatitis (MASH).
Using HistoIndex’s qFibrosis® platform, investigators found significantly greater fibrosis improvement after 48 weeks of treatment compared with placebo, reinforcing previously reported Phase 2 histopathology results and providing additional quantitative evidence of treatment benefit.
Precision Assessment with qFibrosis®
The analysis employed HistoIndex’s proprietary qFibrosis® platform, an AI-powered digital pathology tool that quantifies fibrosis changes with greater sensitivity and reproducibility than conventional categorical scoring. These data complement blinded pathologist assessments previously reported, which showed statistically significant improvements in fibrosis and MASH resolution after 48 weeks.
The findings are particularly notable because fibrosis assessment remains one of the most challenging endpoints in MASH clinical trials. Traditional biopsy scoring can be subject to inter-observer variability, creating growing interest in AI-driven quantitative approaches that provide more objective and reproducible measurements of treatment response.
Trial Design and Patient Cohort
The independent evaluation included 27 protocol-compliant patients with baseline fibrosis stage F1 or higher confirmed by qFibrosis®. Of these, 11 received zabopegdutide and 16 received placebo. Liver biopsy samples were analyzed after 48 weeks of treatment.
Key Findings
Fibrosis Improvement: 81.8% of patients treated with zabopegdutide achieved at least a one-stage improvement in fibrosis compared with 18.8% of placebo-treated patients (p=0.001).
Continuous Fibrosis Reduction: Patients receiving zabopegdutide showed a 41.0% reduction in steatosis-corrected qFibrosis® continuous scores from baseline, compared with a 9.5% increase in the placebo group (p<0.001).
Consistency with histopathology: The AI-derived results closely mirrored findings from conventional histological review, reinforcing the robustness and consistency of the observed treatment effect.
Mechanistic Profile
Zabopegdutide is a liver-targeted GLP-1/glucagon receptor dual agonist with an 11:1 GLP-1-to-glucagon potency ratio. The therapy combines GLP-1-mediated metabolic benefits, including weight loss and improved glycemic control, with glucagon-driven hepatic effects while maintaining a favorable safety and tolerability profile.
Broader Clinical Context
The AI-derived findings build on previously reported Phase 2 results showing statistically significant improvements in fibrosis and MASH resolution after 48 weeks of treatment. The study also demonstrated meaningful reductions in body weight, improvements in glycemic control, reduced liver fat content, lower liver stiffness, and favorable changes in fibrosis biomarkers. Several of these benefits were observed as early as 12 weeks, supporting the therapy’s potential to address both metabolic dysfunction and liver disease progression.
Seulki Lee, PhD, President and CEO of D&D Pharmatech, said the findings strengthen confidence in zabopegdutide’s ability to reverse fibrosis and resolve steatohepatitis.
Dr. Mazen Noureddin, coordinating investigator of the study, noted that quantitative AI pathology provides an additional layer of objectivity and sensitivity when evaluating histological changes and may help advance the development of emerging MASH therapies.
Path Forward
Additional analyses from the qFibrosis® dataset are expected to be presented at upcoming scientific meetings. Together, the blinded histopathology and AI-based assessments provide converging evidence that zabopegdutide may deliver both metabolic and antifibrotic benefits in patients with MASH.
The findings further support continued clinical development of the therapy while highlighting the growing role of AI-powered digital pathology in improving endpoint assessment across MASH clinical trials.
What This Could Mean for Patients
For people living with MASH, fibrosis is a key driver of progression to cirrhosis, liver failure, and cancer. The AI-based analysis adds evidence that zabopegdutide may reverse liver scarring and reduce inflammation, while also improving weight, blood sugar, and liver fat. Though larger studies are needed, these results strengthen confidence in its potential as a future treatment option for patients with MASH and fibrosis.
Reference
About the Writer
Nalam Karthik (LinkedIn) is a healthcare writer and PharmD graduate with interests in pharmacovigilance, drug safety, clinical data analysis, and quality assurance. He is passionate about translating clinical and pharmaceutical knowledge into accessible healthcare content while staying engaged with advancements in drug development and patient safety initiatives.