D&D Pharmatech has linked its GLP-1/glucagon dual receptor agonist to improvements in liver health, keeping the Korean biotech in the hunt for a market already served by Novo Nordisk’s Wegovy.
Patients in the U.S. with metabolic dysfunction-associated steatohepatitis (MASH) now have access to Wegovy and Madrigal Pharmaceuticals’ Rezdiffra. However, while the approvals ended the long wait for MASH drugs, rival companies continue to see opportunities for new products. D&D advanced its pursuit of the market last year by linking 12 weeks of treatment with its asset, zabopegdutide, to a reduction in liver fat.
The biotech continued to track patients in the phase 2 trial through Week 48 to show if zabopegdutide improves fibrosis and resolves MASH. The new data cover the endpoints the FDA advises (PDF) sponsors to use in phase 3 MASH trials.
At Week 48, half of the 16 patients taking 40 mg of zabopegdutide had at least a one-stage improvement in fibrosis and no worsening of MASH, compared with three of 19 people on placebo. Ten of the 16 patients on zabopegdutide had MASH resolution with no worsening of fibrosis, versus one person on placebo, while six people on zabopegdutide and one patient on placebo had fibrosis improvement and MASH resolution.
Placebo-adjusted effect sizes of 34.2% for fibrosis improvement and no worsening of MASH, and 57.2% for MASH resolution and no fibrosis worsening, put zabopegdutide in at least the same ballpark as rival drugs. The caveat is that such cross-trial comparisons can be unreliable, particularly as D&D’s data come from a small study.
Madrigal reported (PDF) placebo-adjusted results of between 8% and 23% at Month 12 of a phase 3 trial. Novo linked Wegovy to placebo-adjusted effect sizes of 14.4% and 28.7% in its phase 3 program. Lilly’s Zepbound, a GLP-1/GIP receptor agonist, achieved placebo-adjusted results ranging from 21% to 53% in a phase 2 study.
Lilly is targeting metabolic dysfunction-associated steatotic liver disease, which can lead to MASH, in its phase 3 program. The study is evaluating tirzepatide—the active ingredient in Zepbound—and Lilly’s investigational triple receptor agonist retatrutide. Boehringer Ingelheim has a GLP-1/glucagon receptor agonist in phase 3 development.
