Gilead reports 75.4% ALP normalization with Livdelzi versus 16.1% placebo in Phase 3 IDEAL, evaluating patients with primary biliary cholangitis.
Written By: Charvi Kalal, PharmD
Reviewed By: Pharmacally Editorial Team
Gilead Sciences reported detailed results from the Phase 3 IDEAL study of Livdelzi® (seladelpar) in adults with primary biliary cholangitis (PBC), demonstrating a substantially higher rate of alkaline phosphatase (ALP) normalization than placebo at Week 52. The findings address a patient population with elevated but relatively lower ALP levels that has historically been underrepresented in pivotal trials of second-line PBC therapies.
At Week 52, 75.4% (49/65) of participants receiving Livdelzi achieved the study’s ALP normalization composite endpoint, compared with 16.1% (5/31) receiving placebo. The results were announced on November 5, 2026, and will be presented at The Liver Meeting 2026. Gilead has also confirmed that the findings have been accepted for publication in the Journal of Hepatology.
Addressing an Underrepresented PBC Population
ALP is an important biochemical marker of cholestatic disease activity in PBC. Elevated levels are associated with an increased risk of disease progression and poorer long-term outcomes, including liver failure.
Historically, randomized clinical trials of second-line PBC therapies have generally required ALP levels above 1.67 times the upper limit of normal (ULN). Consequently, patients with persistent but more modest elevations have been less represented in pivotal clinical studies.
IDEAL was designed to evaluate seladelpar in this population, enrolling adults with ALP above normal but below 1.67× ULN who had inadequately controlled disease despite receiving ursodeoxycholic acid (UDCA) for 12 months or were intolerant to UDCA.
Phase 3 IDEAL Study Design and Results
IDEAL (NCT06060665) was a Phase 3, randomized, double-blind, placebo-controlled study involving 96 adults aged 18–75 years. Participants were assigned to Livdelzi (n=65) or placebo (n=31), with efficacy and safety assessed through Week 52.
The primary endpoint was a composite measure requiring ALP to reach or fall below 1.0× ULN, together with a reduction of at least 15% from baseline.
At Week 52, 75.4% of Livdelzi-treated participants achieved this endpoint, compared with 16.1% in the placebo group, representing a descriptive difference of 59.3 percentage points.
The treatment response was also evident early. At Month 1, 52.3% of participants receiving Livdelzi achieved the composite endpoint, compared with 6.5% receiving placebo. Gilead reported that the response was sustained through Week 52.
These findings extend the evidence for seladelpar beyond populations with more substantial ALP elevations and demonstrate that biochemical normalization is achievable in patients with relatively lower baseline ALP levels.
Safety and Tolerability
The safety profile observed in IDEAL was consistent with previously reported Livdelzi studies, with no new safety concerns identified by Gilead. Overall adverse-event incidence was generally similar between the treatment groups.
Serious adverse events occurred in 3.1% of participants receiving Livdelzi and 12.9% receiving placebo. None of the serious adverse events were considered related to the study drug.
The study also evaluated safety and tolerability through Week 52, alongside exploratory endpoints examining changes in other markers of cholestasis and liver injury. Detailed results for these exploratory measures were not provided in the announcement.
Regulatory Status
Gilead said it will engage with global regulatory authorities to discuss the IDEAL findings. However, the company has not announced specific regulatory submissions or timelines, and the results do not constitute an approval or expansion of Livdelzi’s existing indication.
In the United States, Livdelzi is approved under accelerated approval for adults with PBC who have an inadequate response to UDCA or cannot tolerate it. The approval was based on ALP reduction; improvement in survival or prevention of liver decompensation events has not been demonstrated.
Clinical Interpretation
IDEAL provides additional randomized, placebo-controlled evidence in a population that has received comparatively limited representation in earlier pivotal trials. Its significance lies in extending evidence of seladelpar’s biochemical activity to patients with ALP below the conventional 1.67× ULN trial threshold.
However, the primary endpoint remains biochemical rather than a direct measure of clinical outcomes. The findings do not establish that achieving ALP normalization reduces liver failure, transplantation or mortality. Furthermore, the relatively small study population limits conclusions about uncommon safety events.
Assessment of the complete study results, including exploratory endpoints and longer-term clinical outcomes, will be important in determining whether these biochemical improvements translate into meaningful benefits for patients and influence the broader treatment landscape in PBC.
Reference
Positive Phase 3 IDEAL Study Results Further Support Livdelzi®’s (Seladelpar) Impact on Achieving ALP Normalization Goals in Second-Line Treatment Across a Broad Population of People Living with Primary Biliary Cholangitis (PBC), Gilead Science, 05 November 2026
Intended to Determine the Effects of Seladelpar on Normalization of Alkaline Phosphatase Levels in Subjects with Primary Biliary Cholangitis (PBC) (IDEAL), ClinicalTrials.gov ID NCT06060665
About the Writer
Charvi Kalal (LinkedIn) is a Pharm.D intern and aspiring medical writer with hands-on experience in medical writing, clinical research, pharmacovigilance, and clinical pharmacy. She has experience in medical content writing through CliMed, along with exposure to ADR monitoring, prescription analysis, patient counselling, literature review, and research documentation. Her research focuses on ADR monitoring and reporting in breast cancer patients receiving targeted therapy. With certifications in GCP, biomedical research, scientific writing, and clinical research, she is passionate about transforming scientific evidence into accurate, engaging, and accessible healthcare content.