Livdelzi reduces cholestatic, liver injury markers in patients with PBC and cirrhosis

Key takeaways:

• Patients with PBC and cirrhosis treated with seladelpar exhibited greater reductions in ALP, GGT and ALT at 12 months vs. those on placebo.
• Seladelpar appeared safe and well-tolerated.

SAN DIEGO — Livdelzi appeared safe and well-tolerated and reduced markers of cholestasis and liver injury in patients with primary biliary cholangitis, including those with compensated cirrhosis, according to a presenter.

Previous data from the phase 3, placebo-controlled RESPONSE trial have shown that Livdelzi (seladelpar, Gilead) significantly improved biomarkers of cholestasis over 12 months vs. placebo in patients with primary biliary cholangitis (PBC).

At The Liver Meeting, Alejandra Villamil, MD, of the Italian Hospital of Buenos Aires, presented additional biochemical and safety results for patients with and without cirrhosis.

The trial enrolled 193 patients with PBC and inadequate response or intolerance to ursodeoxycholic acid, who were randomly assigned to daily oral seladelpar 10 mg (n = 128) or placebo (n = 65) for 12 months and were evaluated for changes in alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT) and alanine aminotransferase.

At baseline, all patients had elevated ALP ( 1.67-times the upper limit of normal [ULN]) and total bilirubin ( 2-times ULN), and 14% had Child-Pugh A compensated cirrhosis. Patients with cirrhosis had higher mean liver stiffness vs. those without cirrhosis (18.8 kPa vs. 7.9 kPa), as well has higher ALP (345.8 U/L vs. 309.2 U/L) and total bilirubin (0.97 mg/dL vs. 0.72 mg/dL).

According to study results, seladelpar-treated patients with cirrhosis achieved higher mean change in ALP from baseline to 12 months vs. those on placebo (–121.4 U/L vs. 23.2 U/L), as did those without cirrhosis (–134.8 U/L vs. –18 U/L). Treated patients also demonstrated greater numerical reductions in GGT and ALT, while total bilirubin “remained stable,” Villamil said, regardless of cirrhosis status.

“In and cirrhosis, seladelpar decreased all injury markers, both cholestatic and hepatocellular, compared with placebo, similar to the effects that had been seen in patients without cirrhosis within the RESPONSE trial,” she told attendees.

Among patients with cirrhosis, elevations in ALT or aspartate aminotransferase ( 3-times ULN) and total bilirubin (> 2-times ULN) were reported in one seladelpar-treated patient and two placebo-treated patients.

According to Villamil, the type and incidence of adverse events were similar between groups.

“Patients treated with seladelpar had greater decreases in ALP, GGT and ALT levels compared with those receiving placebo and, concerning liver function and total bilirubin, scores remain stable between the treatment groups,” Villamil said. “Seladelpar does appear safe and well-tolerated in patients with PBC and compensated cirrhosis — the adverse event profile and the incidence of liver enzyme elevation is not very different from the rest of the cohort either with or without compensated cirrhosis.”