D&D Pharmatech (Kosdaq: 347850) has reported 48-week histology data from its Phase II trial of zabopegdutide (DD01) in metabolic dysfunction-associated steatohepatitis. The GLP-1/glucagon dual agonist met all three prespecified biopsy endpoints against placebo in a small but fully randomized, double-blind study.
The DD01-DN-02 study enrolled 67 overweight or obese adults with biopsy-confirmed MASH and fibrosis stage F1–F3 across 12 US centers. Patients received a two-week titration at 20 mg followed by 40 mg once-weekly zabopegdutide or placebo. The 48-week per-protocol population comprised 35 subjects — 16 on active treatment and 19 on placebo — who completed paired liver biopsies and demonstrated high protocol adherence. On the primary histological endpoint of at least one-stage fibrosis improvement with no worsening of MASH, 50% of zabopegdutide-treated patients responded versus 15.8% on placebo, a placebo-adjusted effect size of 34.2% (p=0.0323). MASH resolution with no worsening of fibrosis was achieved by 62.5% of treated patients compared with 5.3% on placebo (placebo-adjusted effect: 57.2%; p=0.0003). The composite endpoint — both fibrosis improvement and MASH resolution — was reached by 37.5% versus 5.3% (placebo-adjusted effect: 32.2%; p=0.0192). These biopsy findings were accompanied by reductions in liver fat measured by MRI-PDFF, liver stiffness by MRE, and fibrosis biomarkers including pro-C3 and ELF. Zabopegdutide was well-tolerated across the full treatment period; the most common adverse events were gastrointestinal, described as mild-to-moderate and transient, with discontinuation rates consistent with other incretin-based therapies.
Zabopegdutide is a once-weekly peptide that co-activates GLP-1 and glucagon receptors. The GLP-1 component drives weight loss and glycemic improvement, while glucagon receptor agonism is intended to enhance hepatic lipid oxidation and contribute directly to antifibrotic activity — a mechanistic rationale for liver-specific benefit beyond what weight reduction alone might produce.
Two therapies now carry US FDA approval for noncirrhotic MASH with moderate-to-advanced fibrosis: Madrigal Pharmaceuticals' Rezdiffra (resmetirom), a selective thyroid hormone receptor-beta agonist approved in March 2024, and Novo Nordisk's Wegovy (semaglutide), a GLP-1 receptor agonist that received MASH approval in August 2025. Both are indicated for F2–F3 fibrosis only, leaving patients with F1 fibrosis outside any approved pharmacotherapy. The DD01-DN-02 study enrolled F1–F3 patients, meaning the dataset includes a population currently unaddressed by approved agents. Cross-trial comparisons are limited by differences in population, sample size, and trial design, and the per-protocol cohort of 35 patients here is substantially smaller than the registrational datasets supporting resmetirom and semaglutide.
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