Seladelpar Safe, Potentially Effective for Cirrhosis in Primary Biliary Cholangitis

Liver with cirrhosis, computer illustration. Cirrhosis is a consequence of chronic liver disease characterized by fibrosis and scarring of tissue.
A team of researchers analyzed the safety, efficacy, and tolerability of seladelpar in patients with compensated liver cirrhosis resulting from primary biliary cholangitis.

Seladelpar was safe, well tolerated, and potentially effective for the treatment of compensated liver cirrhosis among patients with primary biliary cholangitis (PBC), according to study results presented at Digestive Disease Week (DDW), held from May 21 to 24, 2022, in San Diego, California, and virtually.

Patients with compensated cirrhosis associated with PBC are at risk for progression to decompensation, need for transplantation, and death. Risk for disease progression is particularly high for patients who are intolerant to or have incomplete response to ursodeoxycholic acid (UDCA). Seladelpar is a selective peroxisome proliferator-activated receptor (PPAR) delta agonist that has potent anti-cholestatic and anti-pruritic activity and could be a treatment alternative for patients with unmet treatment needs.

The current analysis evaluated safety and efficacy of seladelpar using pooled data from an open-label phase 2 study (ClinicalTrials.gov Identifier: NCT02955602) and a placebo-controlled phase 3 study (ClinicalTrials.gov Identifier: NCT03602560). The subset of patients with PBC and biopsy-diagnosed cirrhosis (n=53) who were intolerant of or were inadequate responders to UDCA received 5 to 10 mg daily seladelpar plus UDCA (if tolerant) for 3 months. Efficacy was defined as alkaline phosphatase (ALP) less than 1.67 per upper limit of normal (ULN), ALP decrease of 15% or higher, total bilirubin (TB) at or below ULN, and changes in liver function.

Study participants were 92% women, had a mean age of 58 years, 94% continued using UDCA, ALP was 287 U/L, TB was 0.92 mg/dL, alanine transaminase (ALT) was 50 U/L, albumin was 3.96 g/dL, and platelets was 197´103/μL.

The patients received 5 mg seladelpar (n=18), 10 mg seladelpar (n=16), or placebo (n=5). At 3 months, the composite endpoint for efficacy was reached by 50%, 63%, and 0% of the 5 mg, 10 mg, and placebo groups, respectively.

ALP was reduced by 31% in the low-dose and by 41% in the high-dose cohorts compared with 2.6% among placebo recipients. A total of 3 patients in each seladelpar group achieved normalized ALP.

Among the 5 mg, 10 mg, and placebo groups, ALT decreased by -6%, -32%, and -15%, respectively.

Total bilirubin, platelets, albumin, and international normalized ratio remained stable.

One patient discontinued seladelpar due to pruritus and 3 patients had a serious adverse event (febrile neutropenia, procedural pain, and angina pectoris).

Compared with the entire trial sample (N=384), the safety and efficacy profiles were similar.

This study was limited by its small sample size.

These data indicated that seladelpar was a safe and potentially effective treatment for compensated liver cirrhosis among patients with PBC with unmet treatment needs.

Reference

Gordon SC, Trivedi P, Bowlus CL, et al. Efficacy, safety, and tolerability of seladelpar in patients with compensated liver cirrhosis due to primary biliary cholangitis (pbc); a pooled analysis of phase 2 and phase 3 studies. Presented at: DDW 2022; May 21-24, 2022; San Diego, CA. Abstract Su1348.