Seladelpar improves markers of cholestasis, reduces pruritus in patients with PBC

Treatment with seladelpar significantly improves serum markers of cholestasis, including alkaline phosphatase (ALP) and total bilirubin (TB), and reduces pruritus in patients with primary biliary cholangitis (PBC) who are at risk for disease progression, according to the RESPONSE trial presented at The Liver Meeting 2023.

This double-blind study evaluated 193 patients (mean age 56.7 years, 94.8 percent female) with PBC, 94 percent of whom received treatment with ursodeoxycholic acid for ≥12 months. Participants were randomly assigned to oral seladelpar 10 mg daily (n=128) or placebo (n=65) for 12 months.

At 12 months, significantly more patients who received seladelpar achieved the primary endpoint of composite response of ALP <1.67 x ULN*, ≥15 percent decrease in ALP from baseline and TB ≤1 x ULN than those on placebo (61.7 percent vs 20 percent; p<0.0001). [The Liver Meeting 2023, abstract 5002]

The ALP level was significantly reduced by 42.4 percent with seladelpar vs 4.3 percent with placebo at month 12 (least square [LS] mean change from baseline, -133.9 vs -16.9 U/L).

Moreover, ALP normalization occurred in 25 percent (p<0.0001) of patients on seladelpar, whereas none was reported in those treated with placebo at month 12.

Seladelpar also significantly reduced serum markers of liver injury (alanine aminotransferase and gamma-glutamyl transferase) and lipid profile (percentage change in low-density lipoprotein cholesterol and triglycerides), the researchers noted.

Key secondary pruritus endpoint

Among patients (37.3 percent) with moderate-to-severe itching (Numerical Rating Scale (NRS) score of ≥4) at baseline, those treated with seladelpar experienced an improvement in pruritus, as shown by a greater reduction in NRS score, at month 6 vs those on placebo (LS mean change from baseline, 3.2 percent vs 1.7 percent; p<0.005), which was sustained through month 12.

The researchers also noted that the reductions in pruritus with seladelpar were associated with improved sleep across all populations.

In terms of safety, the overall rates of treatment-related adverse events (TRAEs) were similar between the seladelpar and placebo arms (86.7 percent vs 84.6 percent), with no serious TRAEs related to the study drug reported.

“Overall, the RESPONSE trial met both the primary and all key secondary endpoints,” said lead author Dr Gideon Hirschfield from Toronto General Hospital, University of Toronto in Toronto, Ontario, Canada.

“Significantly more patients met the composite biochemical endpoint and ALP normalization with seladelpar vs placebo at month 12,” Hirschfield added.

“[Furthermore,] seladelpar appeared safe and well tolerated [in this patient population],” he noted.