Gilead's Livdelzi Demonstrates Sustained Efficacy in Primary Biliary Cholangitis, Offering Alkaline Phosphatase Reduction, Itch Relief and Potential to Slow Disease Progression

Gilead Sciences, Inc. announced new long-term data reinforcing the safety and efficacy profile of Livdelzi (seladelpar) for people living with primary biliary cholangitis (PBC). Findings support Livdelzi's consistent efficacy and safety outcomes in patients switching from obeticholic acid and positive impact on liver stiffness over 3 years. These findings were presented at The Liver Meeting hosted by the American Association for the Study of Liver Diseases (AASLD) 2025 in Washington, D.C. Late-breaking, real-world data on Livdelzi, the only PBC treatment that provides statistically significant reductions across key biomarkers of disease and itch vs.

placebo, support Livdelzi as an effective and well-tolerated alternative for patients switching from obeticholic acid, and as a second-line therapy. Among 396 patients analyzed, 130 switched from obeticholic acid and 266 used Livdelzi as second-line or monotherapy based on data available since US approval in late 2024. Reductions in alkaline phosphatase (ALP) were observed in both groups, with most patients achieving ALP levels below 1.67×ULN.

Safety labs remained stable, and 93% of patients continued Livdelzi treatment throughout the observation period. Gilead will present late-breaking interim results from its Phase 3 ASSURE study (NCT03301506), showing Livdelzi?s potential to improve liver health in people with PBC. After up to three years of treatment, 85% of participants maintained or improved their liver stiffness measurements (LSMs).

Among 114 participants with data at Month 36, the median change from baseline was -0.2 kPa (-2.9%). Notably, those in the highest-risk group (baseline LSM =16.9 kPa) saw a median reduction of -5.2 kPa (-29.7%). New interim results from the open-label Phase 3 ASSURE trial show that 67% (82/122) of participants with PBC achieved a composite biochemical response (CBR), while 34% (41/122) reached normalized ALP levels after three years of treatment with Livdelzi.

These results are consistent with those from the pivotal Phase 3 RESPONSE trial and underscore Livdelzi?s potential to meaningfully impact disease progression and pruritus symptom burden in PBC. Livdelzi continues to show a robust safety profile, with no treatment-related serious adverse events (SAEs) and no new safety signals after up to four years of exposure. Livdelzi delivers sustained and meaningful reduction in chronic itch?a debilitating symptom affecting up to 80% of people with PBC.

Among patients with moderate to severe itch at the start of treatment, over half reported significant improvement, including those who switched from placebo. Benefits were maintained for up to 30 months and supported with validated patient-reported measures such as the pruritus NRS, 5-D Itch, and PBC-40 Itch domain scores. The pruritus numeric rating scale (NRS) used throughout both studies underwent rigorous psychometric validation, demonstrating its reliability and sensitivity to change in the open-label ASSURE study.

Additional analysis from RESPONSE showed that Livdelzi not only reduced itch severity but also impacted the burden itch places on daily life, including the ability to engage in social activities, complete household tasks, and participate in work or school. It also reduced the spread of itch across the body. A separate analysis suggests that Livdelzi may offer meaningful improvements in PBC-related itch, which can impact quality of life for people living with this chronic condition, not just those experiencing moderate or severe itch.

Livdelzi was granted accelerated approval by the U.S. Food and Drug Administration (FDA) in August 2024. ASSURE is an open-label, long-term study to evaluate the safety and tolerability of Livdelzi in people with primary biliary cholangitis (PBC) who have already participated in other PBC clinical trials of Livdelzi. The ASSURE study includes participants from previous studies of Livdelzi in PBC, including the Phase 3 registrational RESPONSE study and legacy clinical trials.

RESPONSE was a pivotal Phase 3, double-blind, placebo-controlled clinical trial designed to evaluate the efficacy and safety of Livdelzi in adults with primary biliary cholangitis (PBC) who have shown inadequate response or intolerance to ursodeoxycholic acid (UDCA). The trial enrolled 193 participants across multiple sites worldwide. RESPONSE assessed the key biomarker of cholestasis alkaline phosphatase (ALP) and other parameters of liver function, as well as secondary endpoints including pruritus and other patient quality of life measurements.

Participants in the RESPONSE trial received a daily oral dose of 10 mg of Livdelzi for 12 months. The trial aimed to help address the high unmet need for effective second-line therapies for individuals with PBC. The approvals of Livdelzi were based primarily on data from the RESPONSE study.