Seladelpar 10mg capsules

Background & aimsApproximately 40% of patients with Primary Biliary Cholangitis (PBC) show incomplete response to ursodeoxycholic acid, thus needing second-line treatment to prevent disease progression. As no head-to-head comparison study is available, we used a network meta-analysis (NMA) to compare efficacy and safety of available second-line therapies.MethodsWe performed a systematic literature review including randomised, placebo-controlled trials of patients with PBC and incomplete response, or intolerance, to ursodeoxycholic acid, and compared relative risks (RRs) for primary (biochemical response at 52-week) and secondary outcomes [incidence of new-onset pruritus and serious adverse events (SAEs)].ResultsThe NMA included three studies, each testing obeticholic acid (OCA), seladelpar or elafibranor versus placebo (active therapy/placebo: 379/191 patients). All treatments significantly increased the RR for biochemical response with an advantage of elafibranor versus seladelpar (RR: 4.37, 95% CI: 1.01-18.87). OCA 5-10 mg/10 mg was associated with a higher risk of new-onset pruritus compared to placebo (RR: 1.43; 95% CI: 1.09-1.88/RR: 1.79; 95% CI: 1.37-2.33), while seladelpar decreased this risk (RR: 0.30; 95% CI: 0.12-0.80). Compared to placebo, OCA 5-10 mg/10 mg was associated with an increased risk of SAE (RR: 3.82; 95% CI: 1.46-10.02/RR 2.67; 95% CI: 1.00-7.08).ConclusionsAmong second line therapies for patients with PBC, elafibranor is slightly more effective in obtaining biochemical response than seladelpar that, on the other hand, is the only drug associated with a lower incidence of pruritus. While of similar efficacy, OCA was associated with increased pruritus and SAEs. These findings may help personalise second-line treatment in patients with PBC.

Abstract licence: CC BY-NC-ND

ABSTRACTBackground and ObjectiveSeladelpar is an oral, once‐daily medication that improves cholestasis through its selective peroxisome proliferator‐activated receptor (PPAR‐δ) agonism. It shows promising efficacy in treating primary biliary cholangitis (PBC) patients.MethodsA systematic review and meta‐analysis synthesizing evidence from randomized controlled trials (RCTs) obtained from PubMed, Cochrane, Scopus, and WOS until July 19th, 2025. Dichotomous outcomes were reported using risk ratio (RR) and continuous outcomes using mean difference (MD), with a 95% confidence interval (CI).ResultsThree RCTs with 499 patients were included. Seladelpar was significantly associated with an increased ALP normalization (RR: 21.12 with 95% CI [4.14, 107.58], p < 0.01), biochemical response (RR: 3.06 with 95% CI [2.00, 4.70], p < 0.01), and decreased pruritus NRS score change (MD: −1.47 with 95% CI [−2.73, −0.21], p = 0.02). Seladelpar was also significantly associated with a decreased incidence of pruritus (RR: 0.54 with 95% CI [0.31, 0.94], p = 0.03) but with an increased incidence of headache (RR: 3.37 with 95% CI [1.11, 10.23], p = 0.03). However, there was no significant difference between seladelpar and placebo regarding the incidence of any adverse events (RR: 0.96 with 95% CI [0.87, 1.06], p = 0.43).ConclusionSeladelpar improved liver biomarkers of cholestasis and reduced pruritus in patients with PBC without significantly increasing the adverse effects. This makes seladelpar a promising addition to the treatments available for PBC.Trial Registration: PROSPERO: CRD42024521208

Abstract licence: CC BY 4.0

Abstract Introduction Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by progressive bile duct destruction, leading to cholestasis and, if untreated, liver failure. Although ursodeoxycholic acid (UDCA) remains the first-line treatment, many patients exhibit an inadequate response, necessitating alternative therapeutic options. Seladelpar, a peroxisome proliferator-activated receptor delta (PPAR-δ) agonist, has emerged as a promising alternative due to its anti-inflammatory and anti-fibrotic properties. Methods A systematic review and meta-analysis of randomized controlled trials (RCTs) were conducted to evaluate the efficacy and safety of Seladelpar in patients with PBC. A comprehensive database search was performed to identify studies comparing Seladelpar with placebo. Primary and secondary outcomes, including alkaline phosphatase (ALP) normalization, biochemical response, and adverse events, were analyzed. Results Three RCTs, comprising 496 patients, were included. Seladelpar significantly improved ALP normalization and biochemical response compared to placebo. Additionally, it effectively reduced ALP and ALT levels from baseline to follow-up. Adverse events, including abdominal pain and headache, were reported, with a higher incidence observed in the Seladelpar group, while other adverse events showed no significant differences between groups. Conclusion Seladelpar appears to be an effective treatment for PBC, demonstrating significant improvements in key liver function markers. While it has shown therapeutic benefits, further research is warranted to evaluate its long-term safety, particularly regarding adverse event incidence, and to determine its efficacy across different dosages.

Abstract licence: CC BY 4.0

Background: Primary biliary cholangitis (PBC) is a progressive autoimmune liver disease marked by destruction of intrahepatic bile ducts, leading to fibrosis, cirrhosis, and liver failure. Current treatments, including ursodeoxycholic acid and obeticholic acid, are often inadequate or associated with adverse effects, highlighting the unmet need for effective, well-tolerated therapies. Seladelpar, a selective peroxisome proliferator-activated receptor delta agonist, has shown promise in improving biochemical markers and clinical outcomes in PBC. This systematic review and meta-analysis evaluates the efficacy and safety of Seladelpar in PBC management. Methods: This review adhered to PRISMA guidelines and was registered with PROSPERO. A systematic search of PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov was conducted up to October 2024, focusing on studies evaluating Seladelpar in adult PBC patients. Randomized controlled trials, observational studies, and open-label extensions reporting efficacy (e.g., alkaline phosphatase [ALP] reduction) or safety outcomes were included. Meta-analysis was performed using RevMan, with pooled estimates presented as weighted mean differences or risk ratios. Results: From 611 studies, seven met inclusion criteria, comprising 1019 participants across Phase 2 and Phase 3 trials and open-label extensions. Seladelpar significantly reduced ALP levels, with a dose-response relationship observed. The 10 mg dose showed the most pronounced efficacy, with a 53–63% ALP reduction compared to placebo. Clinical improvements, including reduced pruritus and enhanced quality of life, were consistent across studies. Long-term follow-up demonstrated sustained biochemical and clinical benefits. Adverse effects were dose-dependent, with pruritus, nausea, and dyspepsia most common. The 5 mg dose had the lowest incidence of adverse events. Conclusions: Seladelpar demonstrates robust efficacy in improving biochemical markers and alleviating symptoms in PBC, with a favorable safety profile. Its potential for long-term clinical benefit underscores its role as a promising therapeutic option for patients with PBC. Further studies are warranted to confirm its long-term safety and efficacy in diverse patient populations.

Abstract licence: CC BY 4.0