Livdelzi shows consistent efficacy in PBC

Another analysis provides evidence supporting that Livdelzi delivered clinically and statistically significant improvements in pruritus. These data and more were presented at the European Association for the Study of the Liver (EASL) Congress 2025 in Amsterdam, Netherlands. 

Livdelzi Efficacy in Participants with Prior Fibrate or Obeticholic Acid Use

An interim analysis from ASSURE (NCT03301506), an ongoing, open-label, long-term study, reinforces the efficacy and safety profile of Livdelzi in people with PBC, including those with prior fibrate or obeticholic acid use. This analysis assesses participants from the pivotal Phase 3 placebo-controlled RESPONSE (NCT04620733) study and after participant rollover into the open-label ASSURE study, with or without prior fibrate or obeticholic acid use.

Among those with 18 months of exposure to Livdelzi, including 12 months in RESPONSE and 6 months in ASSURE, 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). Safety was similar regardless of prior fibrate or obeticholic acid use. No treatment-related serious adverse events (SAEs) were reported.

Livdelzi and Meaningful Change in Pruritus

Up to 80% of people with PBC experience symptoms such as pruritus (chronic itch) and fatigue, both of which can profoundly compromise quality of life. The Pruritus Numeric Rating Scale (NRS) can evaluate treatment effects to see if a therapy is working, as well as examine the meaningful within-person change (MWPC) in the Pruritus NRS that people with PBC with pruritus perceive as a beneficial treatment effect. 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.

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, is a meaningful change. These findings highlight the potential of Livdelzi to address this debilitating symptom.

NRS scores were measured against two anchor analyses, the 7-day recall Patient Global Impression of Severity of pruritus (PGI-S) and the Patient Global Impression of Change of pruritus (PGI-C), which were administered at study visits. The MWPC threshold estimates were validated using distribution-based methods and empirical cumulative distribution function (eCDF) curves. Additionally, previously collected qualitative interviews were used to evaluate meaningful change on the Pruritus NRS in people with PBC with pruritus (NRS≥ 4) outside of the trial.

ASSURE (NCT03301506) 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 III registrational RESPONSE study and legacy clinical trials. Legacy studies include the open label Phase II dose-ranging study (2 mg, 5 mg, or 10 mg Livdelzi), the open label Phase III/IV long-term safety study (5 mg or 10 mg Livdelzi), the Phase III placebo-controlled ENHANCE study (5 mg or 10 mg Livdelzi vs placebo), and the ongoing open label study in people with PBC and hepatic impairment.

RESPONSE (NCT04620733) was a pivotal Phase III, 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 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.

ENHANCE (NCT03602560) was a Phase III, multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the safety and efficacy of seladelpar in participants with primary biliary cholangitis (PBC) and an inadequate response or intolerance to UDCA. The trial investigated the potential of seladelpar to improve biochemical markers of liver function and reduce pruritus, and assessed safety. The ENHANCE study was terminated early due to reasons determined to be unrelated to Livdelzi.(see citation)

"Building on the momentum of Livdelzi’s launch, these new data presented at EASL further reinforce its potential as a meaningful treatment option for people living with PBC,” said Dr. Dietmar Berger, Chief Medical Officer, Gilead Sciences. “We are particularly encouraged by the sustained biochemical response seen with Livdelzi, even among those who previously received fibrates or obeticholic acid. These results strengthen the evidence supporting Livdelzi’s efficacy and tolerability across a broad population of patients, including those seeking alternatives to current therapies. We remain focused on addressing significant unmet needs and driving progress in liver health.”

 “Seladelpar is uniquely positioned as the only once-daily oral treatment that has statistically significant outcomes for both the underlying disease and the burdensome symptom of pruritus in people with PBC,” said Dr.  Alejandra Maria Villamil,  Chief of Autoimmune Liver Diseases Unit Hospital Italiano de Buenos Aires Buenos Aires, Argentina. “The demonstrated improvement in pruritus, combined with its established safety and efficacy profile, reinforces seladelpar as an on-label treatment option for people with PBC.”

Citation- Anon. ENHANCE: Safety and Efficacy of Seladelpar in Patients With Primary Biliary Cholangitis-A Phase 3, International, Randomized, Placebo-Controlled Study.  Gastroenterol Hepatol (N Y)   2021 17(2 Suppl 3):5-6.