Seladelpar safe, effective for primary biliary cholangitis

In patients with primary biliary cholangitis (PBC), the use of seladelpar, a selective peroxisome proliferator-activated receptor-delta agonist, safely improves biochemical markers of cholestasis and inflammation, reports a new study.

Researchers conducted a 52-week, phase II, open-label study which randomly assigned patients to receive 2-mg/day (n=11), 5-mg/day (n=53), or 10-mg/day (n=55) doses of seladelpar. The trial lasted for 12 weeks after which doses could be uptitrated to 10 mg/day depending on initial response. The primary efficacy endpoint was 8-week change in alkaline phosphatase (ALP) level from baseline.

Mean baseline ALP levels were 300, 345, and 295 U/L in the 2-mg, 5-mg, and 10-mg dose groups, respectively. Cirrhosis and pruritus were present in 21 percent and 71 percent of patients at baseline, respectively.

All groups saw significant ALP reductions after 8 weeks of treatment. Those who received 2-mg/day of seladelpar, for instance, reported a mean drop of 26 percent from baseline. The corresponding reductions were 33 percent and 41 percent for the 5-mg and 10-mg cohorts (p≤0.005 for all).

Such responses were maintained or improved even further by week 52, after 91 percent and 80 percent of the 2-mg and 5-mg groups were given dose escalations, respectively. No treatment-related serious adverse events were reported, though four patients eventually dropped out due to side effects.

“Patients with PBC who took seladelpar, a new treatment being developed for PBC, at increasing doses for 1 year had clinically significant, dose-dependent improvements in key liver tests,” the researchers said. “Treatment appeared safe and was not associated with any worsening in patient self-reported itch scores.”