VIENNA — GKT831 achieved rapid dose- and time-dependent reductions in markers of cholestatic bile duct disease and liver injury in patients with primary biliary cholangitis who had an inadequate response to ursodeoxycholic acid, according to a presentation at International Liver Conference 2019.
“Primary biliary cholangitis is a complex disorder with a network of largely unknown genetic and environmental factors,” Pietro Invernizzi, MD, from the University of Milano-Bicocca School of Medicine in Italy, said during his presentation. “It is characterized by non-suppurative granulomatous cholangitis, duct destruction, and portal fibrosis that progress slowly to biliary cirrhosis.”
GKT831, a potent inhibitor of the nicotinamide adenine dinucleotide phosphate, has previously shown marked anti-inflammatory and antifibrotic activity in multiple models of advanced cholestatic diseases.
To assess the safety and efficacy of the therapy, Invernizzi and colleagues enrolled 111 patients with PBC who had been on a stable dose of UDCA with alkaline phosphatase and gamma-glutamyl transpeptidase (GGT) levels 1.5 or more times the upper limit of normal.
The ongoing study will have patients receive 400 mg of GKT831 once a day, twice a day, or placebo for 24 weeks while continuing UDCA treatment.
Results from a 6-week interim analysis showed that patients who received GKT831 twice daily had significantly greater reductions of GGT compared with placebo (–23% vs. –7%; P < .01).
Patients with higher baseline GGT in the twice daily group were especially likely to achieve significant GGT reductions compared with placebo (29% vs. 8%; P < .01). This, Invernizzi said, suggested that GKT381 may also benefit patients with more advanced disease.
Alkaline phosphatase also decreased significantly in patients who received GKT831 twice daily compared with placebo (–17% vs. –2%; P < .001).
“GKT831 is the first non-anticholestatic compound to significantly improve markers of cholestasis, inflammation and fibrosis in PBC,” Invernizzi concluded. “It appears to be well-tolerated with no signals related to pruritus or fatigue.
A full safety profile analysis will be performed at the end of the study along with evaluation of effects on liver fibrosis and patient quality of life. – by Talitha Bennett
Invernizzi P. Abstract GS-02. Presented at: International Liver Congress; April 10-14, 2019; Vienna, Austria.
Disclosures: Healio Gastroenterology and Liver Disease was unable to confirm relative financial disclosures at the time of publication.