Written By: Pharmacally Medical News Desk
Gilead has announced promising new data from its Phase 3 ASSURE trial demonstrating sustained efficacy of Livdelzi® (Seladelpar) in treating Primary Biliary Cholangitis (PBC). The long-term results highlight Livdelzi ability to significantly reduce alkaline phosphatase (ALP), provide meaningful itch relief, and potentially slow disease progression in patients living with this chronic autoimmune liver condition.
The ASSURE trial (Clinical Trial id NCT03301506) enrolled patients with PBC who had an inadequate response to or were intolerant of prior treatments such as ursodeoxycholic acid (UDCA) and obeticholic acid (OCA). Over three years of therapy, 67% (82/122) of participants achieved a composite biochemical response including ALP reduction, with 34% (41/122) reaching normalized ALP levels a key biomarker linked to better clinical outcomes. Livdelzi impact on lowering ALP was sustained long term across diverse patient subgroups, including those switching from OCA.
Beyond biochemical markers, Livdelzi demonstrated robust relief from pruritus (itch), a symptom that affects the majority of PBC patients and substantially decreases quality of life. Over half of patients with moderate to severe baseline itch reported clinically meaningful improvements sustained up to 30 months, assessed by standardized itch scales.
Moreover, the trial showed encouraging effects on liver stiffness measurements (LSM), a non-invasive indicator of liver fibrosis and disease progression. Eighty-five percent of patients experienced stable or improved liver stiffness over the study period, including a notable median 29.7% reduction in the highest-risk patients. These findings suggest Livdelzi’s potential to delay or prevent PBC progression to cirrhosis and liver failure.
The safety profile of Livdelzi remained favorable with no new concerns identified after four years of follow-up, and a high patient adherence rate of 93%. Real-world data from nearly 400 patients reinforced these findings, confirming Livdelzi as an effective and well-tolerated treatment option for PBC, especially amidst recent safety issues limiting alternatives like Ocaliva® (obeticholic acid).
“Livdelzi demonstrated the potential to alter PBC’s course by stabilizing or improving liver stiffness, a key marker of disease progression, especially in high-risk patients treated up to three years,” said Dietmar Berger, MD, PhD, Chief Medical Officer at Gilead Sciences.
Christopher Bowlus, MD, FAASLD, emphasized, “Real-world data support seladelpar as a meaningful alternative to obeticholic acid and an effective second-line therapy. Clinically relevant alkaline phosphatase improvements and a favorable safety profile make it a valuable option for patients with limited treatments.”
About Primary Biliary Cholangitis (PBC)
Primary Biliary Cholangitis (PBC) is a chronic autoimmune liver disease characterized by the gradual destruction of the small bile ducts within the liver. This damage impairs the flow of bile, leading to its buildup, liver inflammation, fibrosis, and eventual scarring (cirrhosis). PBC progresses slowly and often presents initially with symptoms like fatigue and intense itching (pruritus), though some patients remain asymptomatic in early stages. If untreated, the disease can lead to liver failure. The exact cause is unclear but involves immune system dysfunction, potentially triggered by genetic and environmental factors. PBC primarily affects middle-aged women and is diagnosed through elevated liver enzymes, antibody tests, and imaging.
About Livdelzi
Livdelzi® (Seladelpar) is a novel oral therapy approved for the treatment of primary biliary cholangitis (PBC). It is a selective agonist of peroxisome proliferator-activated receptor delta (PPARδ), a nuclear receptor found in many tissues including the liver. Livdelzi mechanism of action primarily involves the activation of PPARδ, which leads to multiple beneficial effects relevant in PBC.
This latest data adds to the increasing momentum behind Livdelzi as a valuable addition to the PBC treatment landscape, following the FDA’s approval and ongoing studies validating its benefits in real-world clinical practice. Activation of PPARδ by Seladelpar reduces bile acid synthesis, a key pathological feature in PBC, by influencing the fibroblast growth factor 21 (FGF21) signaling pathway. This results in the downregulation of cholesterol 7 alpha-hydroxylase (CYP7A1), a crucial enzyme responsible for converting cholesterol into bile acids in the liver. By decreasing CYP7A1 activity, Seladelpar limits the accumulation of toxic bile acids that contribute to liver inflammation, cholestasis, and fibrosis in PBC patients. Livdelzi received accelerated approval from the U.S. Food and Drug Administration (FDA) in August 2024, based primarily on the pivotal Phase 3 RESPONSE trial.
Gilead’s announcement underscores Livdelzi growing role in addressing long-standing unmet needs in PBC care by improving key liver function tests, relieving debilitating itch, and offering hope for altering disease trajectory. These results provide a strong foundation for broader clinical adoption and highlight Livdelzi’s potential to improve outcomes and quality of life for patients with this challenging liver disorder.
References
Gilead’s Livdelzi® Demonstrates Sustained Efficacy in Primary Biliary Cholangitis (PBC), Offering Alkaline Phosphatase (ALP) Reduction, Itch Relief and Potential to Slow Disease Progression, 07 November 2025, Gilead, https://investors.gilead.com/news/news-details/2025/Gileads-Livdelzi-Demonstrates-Sustained-Efficacy-in-Primary-Biliary-Cholangitis-PBC-Offering-Alkaline-Phosphatase-ALP-Reduction-Itch-Relief-and-Potential-to-Slow-Disease-Progression/default.aspx
Seladelpar in Subjects with Primary Biliary Cholangitis (PBC), ClinicalTrials.gov ID NCT03301506, https://clinicaltrials.gov/study/NCT03301506
Mayo MJ et al, Open-label, clinical trial extension: Two-year safety and efficacy results of seladelpar in patients with primary biliary cholangitis. Aliment Pharmacol Ther. 2024 Jan;59(2):186-200. Doi: 10.1111/apt.17755. Epub 2023 Oct 30. PMID: 37904314.
E.J. Lawitz et al, Long-Term Efficacy and Safety of Open-Label Seladelpar Treatment in Patients with Primary Biliary Cholangitis: Pooled Interim Results for up to 3 Years from the ASSURE Study, Digestive and Liver Disease, Volume 57, Supplement 1, 2025, Pages S88-S89, https://doi.org/10.1016/j.dld.2025.01.172.