VIENNA — When patients do not fully respond to ursodeoxycholic acid, a new peroxisome proliferator-activated receptor alpha and delta agonist may offer control for alkaline phosphatase and may even alleviate pruritis, according to new data presented during the International Liver Congress.
“Both doses of elafibranor achieved the primary endpoint of alkaline phosphatase reduction; achieved key secondary composite endpoints aligned to future registrational studies; significantly reduced PBC-related cholestatic markers, IgM, HsCRP and bile acid precursors,” Velimir Luketic, MD, from Virginia Commonwealth University School of Medicine, said during his presentation. “Strong alkaline phosphatase and composite results further justify moving elafibranor into a phase 3 trial in PBC patients with inadequate response to UDCA.
In this phase 2 study, Luketic and colleagues looked at 45 patients with PBC without cirrhosis considered to have inadequate response to UDCA. They randomly assigned these patients to receive 12 weeks of “add-on” oral elafibranor (Genfit) at 80 mg/day (n=14) or 120 mg/day (n = 15) or to receive placebo (n = 14).
Both doses of elafibranor decreased mean ALP compared with placebo (P < .001). Specifically, the 80 mg/day group saw a reduction of 48% and the 120 mg/day group saw a reduction of 41% while the placebo group rose 3%.
“There was a rapid, sustained and persistent reduction in alkaline phosphatase in the two treatment arms but there was no change in the placebo arm,” Luketic said. “More than 90% of the individuals in the treatment arms achieved greater than 20% reduction.”
As alkaline phosphatase (ALP) at 1.67 times the upper limit of normal is the cutoff for measuring response to UDCA, Luketic presented the data showing that, at week 12, the 80 mg/day group 67% of patients were below that level with an ALP reduction of more than 15 and bilirubin within normal limits. At the same time point, 79% of those within the 120 mg/day group met the same parameters. In the placebo group, 6.7% met the same levels.
Luketic noted significant improvements in lipid and inflammatory makers as well as a trend in decreased pruritis in the treatment groups that he suggested should be studied further in a phase 3 study.
“The majority of the subjects in all three arms had stable pruritus during the trial,” he said. “In the placebo arm, there were more individuals who experienced worsened pruritis while in the treatment arm, more individuals experienced improved pruritis.”
Luketic noted one serious adverse event – myasthenia gravis – that was possibly related to the study drug. – by Katrina Altersitz
Luketic V. LB-02. Presented at: International Liver Congress; April 10-14, 2019; Vienna, Austria.
Disclosures: Luketic reports acting as a consultant for Genfit and an investigator on sponsored clinical trials by AbbVie, BMS, Exalenz, Genfit, Gilead, Intercept, Merck and Novartis.