Durability of treatment response after 1 year of therapy with seladelpar in patients with primary biliary cholangitis (PBC): final results of an international phase 2 study

Seladelpar improved measures of pruritus, sleep, and fatigue and decreased serum bile acids in patients with primary biliary cholangitis

“…To As reported elsewhere, seladelpar brought about decreases in biochemical markers of cholestasis: −45% in ALP, −31% in ALT, −32% in GGT in 10 mg treatment group. 25 None of these correlated with reduction in pruritis at the patient level, nor did total bilirubin, FGF-19 or LDH (Figure S3). Biochemical markers of disease do not appear to reflect the changes in pruritus.…”

“…The primary outcome measure was relative change in ALP from baseline to Week 8. Additional pre‐specified analysis included a broad range of serum biochemistry from baseline through 1 year as described elsewhere 25 …”

“…23 [24] 59 [15] 11 [11] 30 [28] 65 [17] 13 [14] 5-D Itch Total (5-25) 10 [5] 12 [5] PBC-40 Itch (0-15) 5 [4] 6 [4] PBC-40 Fatigue (11-55) 32 [11] 30 [11] ALP ULN: 116 U/L 353 [193] 301 [138] ALT ULN: 41 U/L 46 [25] 46 [21] Total bilirubin ULN: of serum total endogenous bile acid levels at baseline was high (data not shown). In patients receiving UDCA, unconjugated and conjugated UDCA comprised 68% of total serum bile acids with GUDCA as the dominant bile acid species (58%).…”

“…Anti-cholestatic activity has been reported in phase 2 studies with PBC patients with incomplete response to UDCA. 24,25 This report describes an analysis of the effects of seladelpar treatment over 1 year in an open label, uncontrolled phase 2 study on patient-reported measures of pruritus, fatigue, and other quality of life (QoL) measures. The relationships of bile acid precursor (7-al pha-hydroxy-4-cholesten-3-one, C4), individual and total bile acids at baseline and after treatment to changes in pruritus are described.…”

<p>Experimental Pharmacological Agents for the Treatment of Primary Biliary Cholangitis</p>

“…Nevertheless, the results of seladelpar in terms of efficacy, safety and tolerability have been presented at EASL Annual meeting 2020 in a 1-year, Phase 2, open label uncontrolled dose-finding study. 38 One hundred and nineteen patients received oral daily doses of 2.5 or 10 mg seladelpar; after 12 weeks doses could be increased up to 10 mg based on biochemical response. Over 1 year seladelpar appeared safe, well tolerated and did not induce pruritus.…”