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

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

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 (DDW 2025) - P3 | "Seladelpar is a first-in-class delpar (selective peroxisome proliferator-activated receptor delta [PPARδ] agonist) indicated for the treatment of PBC in combination with ursodeoxycholic acid (UDCA) in adults who have an inadequate response to UDCA, or as a monotherapy in pts unable to tolerate UDCA. Seladelpar reduced pruritus severity in PBC patients with a durable effect over time and even led to near resolution of itch in some patients, an effect not observed with placebo. Seladelpar mitigated new onset of itch in patients without pruritus and was overall safe and well tolerated regardless of baseline itch."

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

Livdelzi and Meaningful Change in Pruritus (Gilead Press Release) - P3 | N=193 | RESPONSE (NCT04620733) | Sponsor: Gilead Sciences | "Another analysis provides evidence supporting that Livdelzi delivered clinically and statistically significant improvements in pruritus....Using anchor-based analyses, a new study of the qualitative data from the participants of the RESPONSE trial with moderate-to-severe pruritus (NRS ≥ 4) at baseline (n=72) provides evidence supporting that Livdelzi delivered clinically and statistically significant improvements in pruritus.also provides sustained biochemical response in adults with PBC regardless of prior treatment history....Results demonstrated that MWPC estimates of ≥ 3-points on the Pruritus NRS corresponded to 'moderate improvement' as validated by PGI-C and 1-category improvement for PGI-S anchors. The data overall, including half of those interviewed (n=6/12), suggest a 3-point improvement in Pruritus NRS, as seen with seladelpar in the RESPONSE study..."

P3 data • Primary Biliary Cholangitis • Pruritus

COMPARING THE SAFTEY AND EFFICACY OF SECOND LINE THERAPIES FOR PBC WITH OBETHICOLIC ACID: A NETWORK META-ANALYSIS (DDW 2025) - "Introduction: Ursodeoxycholic acid (UDCA), the gold standard therapy for Primary Biliary Cholangitis (PBC) slows disease progression by improving biochemical markers of liver function, particularly alkaline phosphatase (ALP) levels...The second-line therapy, obeticholic acid (OCA), provides an alternative but is associated with significant adverse effects, including pruritus, a debilitating symptom of PBC...Comparison was done between different doses of OCA (5 mg, 10 mg, 50 mg), Elafibranor (80 mg), Seladelpar (10 mg) and Saroglitazar (2 mg and 4 mg) against placebo... Elafibranor demonstrates superior outcomes in achieving biochemical response and improvement in pruritus symptoms when compared to OCA. Additionally, OCA worsened pruritus in PBC patients. Our findings highlight the need for additional randomized controlled trials (RCTs) investigating Elafibranor as effective second line therapy and a potential first line monotherapy for PBC."

Retrospective data • Dermatology • Hepatology • Primary Biliary Cholangitis • Pruritus

EFFICACY AND SAFETY OF SELADELPAR IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS AND COMPENSATED CIRRHOSIS IN THE PHASE 3 PLACEBO-CONTROLLED RESPONSE TRIAL (DDW 2025) - P3 | No abstract available

Clinical • P3 data • Fibrosis • Hepatology • Immunology • Primary Biliary Cholangitis

EFFICACY AND SAFETY OF SELADELPAR IN THE TREATMENT OF PRIMARY BILIARY CHOLANGITIS: A SYSTEMATIC REVIEW AND META-ANALYSIS (DDW 2025) - "Further large-scale studies are warranted to confirm these findings and refine dosing strategies. Keywords : Primary Biliary Cholangitis, Seladelpar, PPAR-δ, Alkaline Phosphatase, Pruritus"

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

SAFETY AND EFFICACY OF DIFFERENT DOSES OF SELADELPAR IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS: A NETWORK META-ANALYSIS (DDW 2025) - "Seladelpar is a peroxisome proliferator-activated receptor-delta (PPAR-δ) agonist which shows promise in managing PBC, particularly for patients intolerant to ursodeoxycholic acid (UDCA). This network meta-analysis underscores the efficacy of seladelpar 10 mg in improving biochemical markers of PBC compared to lower doses and placebo. While lower doses showed varying effectiveness, they were associated with higher rates of adverse events. These findings highlight the need for cautious dose selection in clinical practice to optimize therapeutic benefits while minimizing risks in PBC management with seladelpar."

Retrospective data • Cholestasis • Dermatology • Fatigue • Hepatology • Immunology • Inflammation • Pain • Primary Biliary Cholangitis • Pruritus

Gilead to Present Latest Advancements Across Primary Biliary Cholangitis and Viral Hepatitis (Businesswire) - "New data to be presented at EASL will include a subgroup analysis from ASSURE, an ongoing open-label study, and an analysis of the Phase 3 RESPONSE trial and the open-label extension. Data will reinforce the effectiveness of Livdelzi (seladelpar), known as Lyvdelzi in the European Union, in reducing pruritus (chronic itch), a debilitating common symptom of primary biliary cholangitis (PBC). Moreover, the results will highlight seladelpar’s ability to deliver a sustained biochemical response regardless of prior treatment history, and as an option for a broad range of people with PBC....Key findings from 29 accepted abstracts will include two oral presentations showcasing new data on the critical goal of maintained virologic response following treatment with 2 mg and 10 mg bulevirtide in people living with hepatitis delta virus (HDV). These findings build on the wealth of long-term data for the treatment of chronic HDV."

Clinical data • Hepatitis B • Primary Biliary Cholangitis

IDEAL: Intended to Determine the Effects of Seladelpar on Normalization of Alkaline Phosphatase Levels in Subjects With Primary Biliary Cholangitis (PBC) (clinicaltrials.gov) - P3 | N=90 | Active, not recruiting | Sponsor: Gilead Sciences | Recruiting ➔ Active, not recruiting

Enrollment closed • Hepatology • Immunology • Primary Biliary Cholangitis

EFFICACY AND SAFETY OF SELADELPAR IN PRIMARY BILIARY CHOLANGITIS (PBC): A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS (DDW 2025) - "Seladelpar, a selective PPAR-δ agonist, has shown promise in patients with PBC, particularly in those unresponsive to ursodeoxycholic acid (UDCA). Seladelpar significantly reduced ALP levels in PBC patients, though no improvements were observed in bilirubin levels or pruritus scores. The increased risk of abdominal pain and nausea suggests the need for further research. Larger trials are needed to provide stronger evidence on both the efficacy and safety of Seladelpar in PBC treatment."

Retrospective data • Review • Dermatology • Fatigue • Hepatology • Immunology • Infectious Disease • Inflammation • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Pain • Primary Biliary Cholangitis • Pruritus • Respiratory Diseases

Competitive Ligand-Induced Recruitment of Coactivators to Specific PPARα/δ/γ Ligand-Binding Domains Revealed by Dual-Emission FRET and X-Ray Diffraction of Cocrystals. (PubMed, Antioxidants (Basel)) - "Single-FRET revealed that the respective PPARα/δ/γ-selective agonists (pemafibrate, seladelpar, and pioglitazone) induced the dissociation of the two corepressor peptides, NCoR1 and NCoR2, from the PPARα/δ/γ-LBDs and the recruitment of the two coactivator peptides, CBP and TRAP220. This illustrates that these coactivators bound to the same PPARα-LBD loci via their consensus LXXLL motifs in the liganded state; that NCoR1/NCoR2 corepressors bound to the same loci via the IXXXL sequences within their consensus LXXXIXXXL motifs in the unliganded state; and that ligand activation induced AF-2 helix 12 formation that interfered with corepressor binding and created a binding space for the coactivator. These PPARα/γ-related biochemical and physicochemical findings highlight the coregulator dynamics on limited PPARα/δ/γ-LBDs loci."

Journal • MED1 • NCOR1 • NCOR2 • PPARA • PPARG

Seladelpar treatment of patients with primary biliary cholangitis improves the GLOBE score and predicts improved transplant-free survival (EASL 2025) - No abstract available

Clinical • Hepatology • Immunology • Primary Biliary Cholangitis • Transplantation

Safety of seladelpar in primary biliary cholangitis patients with cirrhosis and clinical signs of portal hypertension: data from the ENHANCE and RESPONSE studies (EASL 2025) - No abstract available

Clinical • Cardiovascular • Fibrosis • Hepatology • Immunology • Portal Hypertension • Primary Biliary Cholangitis

Gilead: Creating change today: Lowering risk, lowering burden of PBC in practice (EASL 2025) - "Sponsored by Gilead. This session aims to provide practical guidance and expert insights on the use of seladelpar in the clinical practice."

Primary Biliary Cholangitis

Gilead: Creating change today: Lowering risk, lowering burden of PBC (EASL 2025) - "Sponsored by Gilead. Describe the overall epidemiology and holistic burden of PBC from a biochemical, symptomatic and patient perspectiveExamine the current landscape for the diagnosis and treatment of PBC, including current unmet needs, challenges and future treatment goalsEvaluate evolving options for second line treatment of PBC, including Seladelpar, and opportunities to optimise outcomes for patients"

Primary Biliary Cholangitis

Pharmacokinetics, safety, and tolerability of seladelpar in people with renal impairment (EASL 2025) - "Background and Aims: Seladelpar is a first-in-class delpar (selective PPAR-delta agonist) indicated for the treatment of primary biliary cholangitis in combination with ursodeoxycholic acid (UDCA) in adults who have an inadequate response to UDCA, or as monotherapy in people unable to tolerate UDCA. Exposure to seladelpar was not meaningfully increased with different degrees of RI and appeared safe and well tolerated regardless of RI status following a single 10 mg dose. The data support that dose adjustment is not necessary for people with mild, moderate, or severe RI receiving seladelpar treatment."

Clinical • PK/PD data • Hepatology • Immunology • Nephrology • Primary Biliary Cholangitis • Renal Disease

Evaluation of the potential impact of seladelpar on the pharmacokinetics of midazolam, tolbutamide, simvastatin, rosuvastatin, and atorvastatin (EASL 2025) - "Background and Aims: Seladelpar is a first-in-class oral delpar (selective PPAR-delta agonist) indicated for the treatment of primary biliary cholangitis in combination with ursodeoxycholic acid (UDCA) in adults who have an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA. Seladelpar did not significantly impact the PK of sensitive probe substrates including midazolam (CYP3A4), tolbutamide (CYP2C9), simvastatin (CYP3A4 and OATP), rosuvastatin (OATP and BCRP), and atorvastatin (CYP3A4 and OATP). Based on these data, it is unlikely that seladelpar would have a clinically significant impact on drugs that are substrates of CYP3A4, CYP2C9, OATP, or BCRP."

PK/PD data • Breast Cancer • Dyslipidemia • Hepatology • Immunology • Obesity • Oncology • Primary Biliary Cholangitis • Solid Tumor • CYP2C9 • CYP3A4

Clinical meaningful change of pruritus numeric rating scale in adults with primary biliary cholangitis with moderate-to-severe pruritus (EASL 2025) - P3 | "Triangulation of anchor, eCDF, distribution-based analyses, and qualitative interviews of patient perception of benefit suggest a 3-point improvement in Pruritus NRS as seen with seladelpar in RESPONSE is meaningful to PBC patients with moderate-to-severe itch."

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