Livdelzi (seladelpar) / Gilead, Kaken Pharma - LARVOL DELTA

Reviewing novel findings and advances in diagnoses and treatment of primary biliary cholangitis. (PubMed, Expert Rev Gastroenterol Hepatol) - "The first-line treatment remains ursodeoxycholic acid, although at least one third of patients has an inadequate response. In 2024 the authorization for obeticholic acid, a farnesoid X receptor agonist previously approved in 2016, was revoked; thus fibrates, particularly bezafibrate, are considered as second-line treatments that improve biochemical markers and potentially decrease long-term outcomes. Alternative options are agents targeting peroxisome proliferator-activated receptors, such as elafibranor and seladelpar, that demonstrated efficacy in clinical trials. Novel approaches for managing symptoms like fatigue and pruritus are also at disposal. Despite these advances, challenges remain in optimizing care delivery and developing treatments that definitively alter the disease progression."

Journal • Review • Dermatology • Fatigue • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus

Emerging Therapeutics for Primary Biliary Cholangitis. (PubMed, Korean J Gastroenterol) - "Ursodeoxycholic acid (UDCA) has been the standard first-line therapy, but up to one-third of patients show an unsatisfactory response to UDCA, underscoring the need for novel treatments. Obeticholic acid is an approved second-line treatment targeting the farnesoid X receptor, but it is associated with adverse effects such as pruritus and the potential risk of hepatic decompensation in patients with advanced disease. Recently, selective peroxisome proliferator-activated receptor (PPAR) agonists, including seladelpar (a PPAR-δ agonist) and elafibranor (dual PPAR-α/δ agonist), have shown substantial efficacy and favorable safety profiles in phase three clinical trials. In addition, emerging therapeutics for symptom relief, such as NOX inhibitors and ileal bile acid transporter inhibitors, further expand the treatment options. These advances offer new opportunities for the improved management of patients with PBC."

Journal • Review • Dermatology • Fibrosis • Gastroenterology • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • Primary Biliary Cholangitis • Pruritus

Long-term efficacy and safety of open-label seladelpar in primary biliary cholangitis: pooled interim results up to 3 years from ASSURE (BSG 2025) - P1, P2, P3 | "Introduction ASSURE (NCT03301506) is an ongoing, open-label, long-term, Phase 3 trial of seladelpar—a first-in-class delpar (selective PPAR-delta agonist)—in patients (pts) with primary biliary cholangitis (who had an inadequate response or intolerance to first-line ursodeoxycholic acid) rolling over from the Phase 3, placebo-controlled, registrational RESPONSE trial (NCT04620733) or with prior participation in legacy trials (Phase 3 ENHANCE [NCT03602560], CB8025-21629 [NCT02955602], CB8025-31731 [NCT03301506], CB8025-21838 [NCT04950764]). There were no treatment-related serious AEs.Download figure Open in new tab Download powerpoint Abstract P197 Figure 1 Conclusions By M30 of the long-term ASSURE study, seladelpar resulted in a durable and sustained biochemical response in 81% of pts, with an ALP normalisation rate of 41%, and robust improvement in pruritus. Seladelpar continues to appear safe and well tolerated, with no new safety signals or change in..."

Clinical • Dermatology • Fibrosis • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus

Attenuation, near resolution, and prevention of pruritus in patients with primary biliary cholangitis receiving seladelpar: a secondary analysis from RESPONSE (BSG 2025) - P3 | "In the Phase 3 RESPONSE trial (NCT04620733), seladelpar, a first-in-class delpar (selective PPAR-delta agonist), significantly decreased pruritus in PBC patients with moderate-to-severe pruritus (numerical rating scale [NRS] ≥4 at baseline) vs placebo; here, we further evaluated pruritus patterns in RESPONSE.Methods Patients with PBC who received ursodeoxycholic acid (UDCA) for ≥12 months or were UDCA intolerant and had alkaline phosphatase ≥1.67x upper limit of normal (ULN) and total bilirubin ≤2x ULN were randomised 2:1 to receive daily oral seladelpar 10 mg or placebo for 12 months. Adverse events were reported in 88.9% and 84.3% of patients with baseline NRS ≥4 and NRS <4, respectively, with similar proportions across treatment arms.Download figure Open in new tab Download powerpoint Abstract P203 Figure 1 Conclusions Seladelpar reduced pruritus severity in PBC patients with a durable effect over time and even led to near resolution of itch in some patients,..."

Clinical • Dermatology • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus

Alkaline phosphatase changes with seladelpar across subgroups of primary biliary cholangitis patients in the RESPONSE trial (BSG 2025) - P3 | "In the pivotal, Phase 3, placebo-controlled RESPONSE trial (NCT04620733), seladelpar, a first-in-class delpar (selective PPAR-delta agonist), led to a significantly higher percentage of PBC patients achieving the composite biochemical endpoint (ALP <1.67x upper limit of normal [ULN], ALP decrease ≥15%, and total bilirubin [TB] ≤ULN) compared to placebo (61.7% vs 20%) and decreased mean ALP levels after one year (-42.4% vs -4.3%, respectively); here, we report additional data on ALP changes in the RESPONSE trial.Methods PBC patients who received ursodeoxycholic acid (UDCA) for ≥12 months or were UDCA intolerant and had ALP ≥1.67x ULN and TB ≤2x ULN were randomised 2:1 to daily seladelpar 10 mg or placebo. Substantial ALP decreases were also observed in patients who did not meet the composite endpoint criteria at month 12. Seladelpar was overall safe and well tolerated, regardless of baseline ALP level."

Clinical • Fibrosis • Hepatology • Immunology • Primary Biliary Cholangitis

Efficacy and safety of peroxisome proliferator-activated receptor agonists in primary biliary cholangitis: a systematic review and meta-analysis (BSG 2025) - "Ursodeoxycholic acid (UDCA) is the standard treatment, but up to 40% of patients are non-responders...This study evaluates the efficacy and safety of PPAR agonists for PBC management.Methods A systematic review and meta-analysis were performed, including eight randomized controlled trials (RCTs) evaluating selective PPAR agonists (fenofibrate, seladelpar) and multi-subtype PPAR agonists (bezafibrate, saroglitazar, elafibranor)...However, their effect on ALT, AST, and pruritus remains limited. Further studies with larger sample sizes and longer durations are required to fully explore the therapeutic potential of PPAR agonists in managing PBC."

Retrospective data • Review • Cholestasis • Dermatology • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Liver Failure • Primary Biliary Cholangitis • Pruritus

Efficacy and safety of seladelpar in patients with primary biliary cholangitis and compensated cirrhosis in the phase 3 RESPONSE trial (BSG 2025) - P3 | "In a prespecified subgroup analysis of the Phase 3, placebo-controlled RESPONSE trial (NCT04620733) of seladelpar, a first-in-class delpar (selective PPAR-delta agonist), a higher percentage of patients with cirrhosis met the composite biochemical endpoint (alkaline phosphatase [ALP] 3x ULN occurred in 1 (5.6%) patient with cirrhosis on seladelpar vs 2 (22.2%) placebo patients.Download figure Open in new tab Download powerpoint Abstract P200 Figure 1 Conclusions Seladelpar reduced biomarkers of cholestasis and liver injury in PBC patients with compensated cirrhosis and in patients without cirrhosis. Seladelpar was overall safe and well tolerated in patients with and without cirrhosis."

Clinical • P3 data • Cholestasis • Fibrosis • Hepatology • Immunology • Liver Failure • Primary Biliary Cholangitis

Long-term safety of seladelpar 10 mg with up to 5 years of treatment in patients with primary biliary cholangitis (BSG 2025) - P3 | "Introduction The Phase 3, placebo-controlled RESPONSE study (NCT04620733) of seladelpar, a first-in-class delpar (selective PPAR-delta agonist), in primary biliary cholangitis (PBC) patients with an inadequate response or intolerance to ursodeoxycholic acid demonstrated significant improvements in cholestatic markers and pruritus with seladelpar over 1 year and similar proportions of adverse events (AEs) and serious AEs (SAEs) between the seladelpar and placebo groups. The exposure-adjusted patient incidence (per 100 patient-years) for patients treated with placebo was 132 for AEs (rate reflective of shorter exposure time for placebo patients), 7.8 for SAEs, 12.2 for Grade ≥3 AEs, and 13.3 for liver-related AEs (with other AEs of interest occurring at lower rates). AEs leading to treatment discontinuation occurred in 2.9 patients per 100 patient-years in seladelpar patients and 5.6 per 100 patient-years in placebo patients.View this table:View inline View popup..."

Clinical • Dermatology • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus

The Treatment of Primary Biliary Cholangitis: Time for Personalized Medicine. (PubMed, Clin Rev Allergy Immunol) - "Bezafibrate, Seladelpar, and IBAT inhibitors have demonstrated significant therapeutic potential in pruritus. Therefore, early prediction and evaluation criteria at baseline and 1-month treatment will help in timely interventions for patients with insufficient efficacy. This improved identification strategy is expected to provide precise and personalized treatment for PBC patients."

Journal • Review • Cholestasis • Dermatology • Fatigue • Fibrosis • Hepatology • Immunology • Inflammation • Primary Biliary Cholangitis • Pruritus

ALKALINE PHOSPHATASE CHANGES WITH SELADELPAR ACROSS SUBGROUPS OF PRIMARY BILIARY CHOLANGITIS PATIENTS IN THE RESPONSE TRIAL (UEGW 2025) - No abstract available

Clinical • Hepatology • Immunology • Primary Biliary Cholangitis

ATTENUATION, NEAR RESOLUTION, AND PREVENTION OF PRURITUS IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS TREATED WITH SELADELPAR: A SECONDARY ANALYSIS OF PATTERNS OF PRURITUS CHANGE IN THE RESPONSE TRIAL (UEGW 2025) - No abstract available

Clinical • Dermatology • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus

EFFICACY AND SAFETY OF SELADELPAR IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS PREVIOUSLY TREATED WITH FIBRATES OR OBETICHOLIC ACID (UEGW 2025) - No abstract available

Clinical • Hepatology • Immunology • Primary Biliary Cholangitis

Gilead's rare liver drug lands fast-track tag in Korea as rival Ipsen circles approval (Korea Biomedical Review) - "The Ministry of Food and Drug Safety (MFDS) on Saturday stamped Livdelzi with a Global Innovative Products on Fast Track (GIFT) tag, slashing the review clock to 90 working days and assigning a dedicated team....Trial data helped Livdelzi earn its ticket. In the phase 3 RESPONSE study, 62 percent of patients on seladelpar met a composite alkaline phosphatase (ALP) endpoint at 12 months versus 20 percent on placebo, and a quarter hit full ALP normalization."

Fast track • Primary Biliary Cholangitis

Long-term Efficacy and Safety of Selective PPARδ Agonist Seladelpar in Primary Biliary Cholangitis: ASSURE Interim Study Results. (PubMed, Am J Gastroenterol) - "Seladelpar demonstrated durable improvements in cholestatic biomarkers and pruritus in patients with PBC with up to 2 years of treatment and remained overall safe with long-term use."

Journal • Cholestasis • Dermatology • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus

Unveiling the therapeutic potential of artopetelin flavonoids through computational approaches as peroxisome proliferator-activated receptor-delta (PPARδ) agonists. (PubMed, J Mol Graph Model) - "Molecular docking (MD) calculations identified six artopetelin ligands with binding affinities surpassing those of the native ligand (-10.4 kcal/mol) and the reference drugs such as elafibranor (-10.0 kcal/mol) and seladelpar (-9.8 kcal/mol). Pharmacokinetic predictions via pkCSM indicated favorable drug-likeness and ADMET profiles. These preliminary in silico findings highlight the strong potential of top five artopetelin flavonoids as PPARδ activators for type 2 diabetes management, underscoring their promise as plant-derived therapeutic agents and warranting further experimental validation."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Advancing care in primary biliary cholangitis: emerging insights and novel therapies. (PubMed, Expert Opin Pharmacother) - "Ursodeoxycholic acid (UDCA) has been the mainstay of therapy for over 40 years...Notably, seladelpar and elafibranor, two selective agonists of peroxisome proliferator-activated receptors, achieved high rates of biochemical response and good tolerability, leading to their recent approval for second-line treatment of PBC...- Personalized treatment approaches for PBC are both feasible and essential to improve biochemical response, extend transplant-free survival and alleviate symptom burden. Well-tolerated novel therapies are poised to reshape the treatment landscape in the near future."

Journal • Review • Cholestasis • Dermatology • Fatigue • Fibrosis • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus • Transplantation

Peroxisome Proliferator-Activated Receptor (PPAR) Agonists for Patients With Primary Biliary Cholangitis With Inadequate Response to Ursodeoxycholic Acid (UDCA): A Systematic Review and Meta-Analysis of Randomized Controlled Trials. (PubMed, JGH Open) - "However, further studies with larger sample sizes, longer follow-up durations, and a focus on patient-centered outcomes are necessary. Additionally, exploring combination therapies and mechanistic insights will help us fully realize the therapeutic potential of PPAR agonists in PBC."

Journal • Retrospective data • Review • Dermatology • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus

Emerging role of peroxisome proliferator-activated receptor agonists in the treatment of cholestatic liver disease. (PubMed, Curr Opin Gastroenterol) - "This review highlights the evolving role of PPAR agonists as second-line agents for PBC and investigational treatments for PSC."

Journal • Review • Cholestasis • Dermatology • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus

Efficacy and Safety of Novel Oral Anti-Cholestatic Agents for Primary Biliary Cholangitis: Meta-Analyses and Systematic Review. (PubMed, Pharmaceuticals (Basel)) - "While ursodeoxycholic acid (UDCA) is the first-line therapy, approximately 40% of patients have incomplete responses, necessitating alternative treatments...Novel agents included seladelpar, fenofibrate, saroglitazar, bezafibrate, elafibranor, and budesonide...However, study heterogeneity and limited long-term data restrict direct comparisons. Larger standardized trials with extended follow-up are needed to confirm long-term efficacy and safety."

Journal • Review • Cholestasis • Dermatology • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus

Game Changers: Blockbuster Small-Molecule Drugs Approved by the FDA in 2024. (PubMed, Pharmaceuticals (Basel)) - "Notably, eight of these drugs (including Rezdiffra®, Voydeya®, Iqirvo®, Voranigo®, Livdelzi®, Miplyffa®, Revuforj®, and Crenessity®) are classified as "first-in-class" and have received breakthrough therapy designation. These agents not only exhibit distinct mechanisms of action but also offer substantial improvements in efficacy for patients compared to prior therapeutic options. This article offers a comprehensive analysis of the mechanisms of action, clinical trials, drug design, and synthetic methodologies related to representative drugs, aiming to provide crucial insights for future pharmaceutical development."

FDA event • Journal • Review • Alopecia • Brain Cancer • Breast Cancer • Cardiovascular • Chronic Kidney Disease • Chronic Obstructive Pulmonary Disease • CNS Disorders • Congenital Adrenal Hyperplasia • Cystic Fibrosis • Dermatology • Duchenne Muscular Dystrophy • Endocrine Disorders • Frontotemporal Lobar Degeneration • Genetic Disorders • Glioma • Hematological Disorders • Hematological Malignancies • Hepatology • Hypertension • Immunology • Infectious Disease • Leukemia • Lung Cancer • Lysosomal Storage Diseases • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Muscular Dystrophy • Nephrology • Non Small Cell Lung Cancer • Oncology • Primary Biliary Cholangitis • Psychiatry • Pulmonary Disease • Renal Disease • Respiratory Diseases • Schizophrenia • Solid Tumor • Ventricular Tachycardia

PPAR-mediated reduction of lipid accumulation in hepatocytes involves the autophagy-lysosome-mitochondrion axis. (PubMed, Ann Med) - "HepG2 cells were treated with oleate/palmitate (O/P) to induce lipid accumulation and exposed to the PPARα agonist fenofibric acid, the γ agonist pioglitazone, the δ agonist seladelpar, or the dual α/γ agonist saroglitazar. All PPAR agonists were able to promote the clearance of lipids in cells loaded with long-chain fatty acids. The key role of acid hydrolysis to generate fatty acids, which can be then catabolized in the mitochondria, and the ability of the PPAR system to sustain each phase of this clearing process were elucidated."

Journal • PPARA • TFEB

LONG-TERM EFFICACY AND SAFETY OF OPEN-LABEL SELADELPAR TREATMENTS IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS: POOLED INTERIM RESULTS FOR UP TO 3 YEARS FROM THE ASSURE STUDY (DDW 2025) - P1, P2, P3 | "The parent studies required an inadequate response or intolerance to first-line ursodeoxycholic acid. By M30 of the long-term ASSURE study, seladelpar resulted in a durable and sustained biochemical response in 81% of pts, with an ALP normalization rate of 41%, and robust improvement in pruritus. Seladelpar continues to appear safe and well tolerated, with no new safety signals or change in frequency of AEs with up to 3 years of exposure."

Clinical • Dermatology • Fibrosis • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus

EFFICACY AND SAFETY OF SELADELPAR AS MONOTHERAPY IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS AND INTOLERANCE TO URSODEOXYCHOLIC ACID (DDW 2025) - P3 | "Efficacy and safety results for seladelpar monotherapy were similar to results previously observed for seladelpar combined with UDCA. Seladelpar 10 mg monotherapy led to notable CBR rates and ALP reductions. Overall, seladelpar monotherapy was well tolerated and had a similar safety profile compared to placebo."

Clinical • Monotherapy • Cholestasis • Hepatology • Immunology • Primary Biliary Cholangitis

Gilead’s Livdelzi (Seladelpar) Demonstrated Consistent Efficacy and Safety Regardless of Prior Treatment History in New Data Presented at EASL 2025 (Gilead Press Release) - P3 | N=500 | ASSURE (NCT03301506) | P3 | N=193 | RESPONSE (NCT04620733) | Sponsor: Gilead Sciences | "Gilead Sciences...today announced new data from multiple analyses which reinforce that Livdelzi (seladelpar)...is effective and generally well-tolerated for the treatment of primary biliary cholangitis (PBC) and also provides sustained biochemical response in adults with PBC regardless of prior treatment history...60% (9/15) of participants with prior fibrate or obeticholic acid use achieved the composite biochemical response, as compared to 62% (54/87) of those without prior fibrate or obeticholic acid use. Among participants who started Livdelzi in ASSURE after previously receiving placebo in RESPONSE, 64% (7/11) of participants with prior fibrate or obeticholic acid use, as compared to 78% (32/41) of participants without prior fibrate or obeticholic acid use achieved the composite biochemical response after 6 months of receiving Livdelzi (Month 6 of ASSURE)."

P3 data • Primary Biliary Cholangitis

ALKALINE PHOSPHATASE CHANGES WITH SELADELPAR ACROSS SUBGROUPS OF PRIMARY BILIARY CHOLANGITIS PATIENTS IN THE RESPONSE TRIAL (DDW 2025) - P3 | " Patients with PBC who received ursodeoxycholic acid (UDCA) for ≥12 months or were UDCA intolerant and had ALP ≥1.67 × ULN and TB ≤2 × ULN were randomized 2:1 to daily seladelpar 10 mg or placebo. Seladelpar led to robust and consistent ALP decreases across all subgroups studied. Substantial ALP decreases were also observed in patients who did not meet the composite endpoint criteria at Month 12. Seladelpar was overall safe and well tolerated, regardless of baseline ALP level."

Clinical • Fibrosis • Hepatology • Immunology • Primary Biliary Cholangitis