IDEAL: Seladelpar Achieves ALP Normalization in Second-Line PBC

Seladelpar (Livdelzi) achieved alkaline phosphatase (ALP) normalization in 75.4% of patients with primary biliary cholangitis (PBC) and baseline ALP below 1.67 times the upper limit of normal (ULN), compared with 16.1% on placebo, in the phase 3 IDEAL trial. Gilead Sciences announced the Week 52 results, which are being presented at The Liver Meeting 2026, hosted by the American Association for the Study of Liver Diseases (AASLD), November 5–9 in Denver, Colorado.1

“People with PBC whose alkaline phosphatase remains elevated but below 1.67 times the upper limit of normal have been largely excluded from previous pivotal trials of second-line therapies,” Cynthia Levy, MD, University of Miami Miller School of Medicine, said in a statement.1 “IDEAL provides randomized, placebo-controlled evidence that seladelpar can improve biochemical response in this population. These findings can inform individualized treatment discussions, taking into account each individual’s risk of disease progression, symptoms, and potential benefits and risks of additional therapy.”

According to Gilead, IDEAL is the first trial of seladelpar in patients with inadequately controlled disease within this ALP range. The company noted a threshold of 1.67× ULN has historically been required for inclusion in PBC randomized trials, leaving patients below this cutoff largely unstudied.1

The oral peroxisome proliferator-activated receptor delta (PPAR-δ) agonist received accelerated approval from the US Food and Drug Administration (FDA) in August 2024, based on ALP reduction in the phase 3 RESPONSE trial.1,2

How Did Seladelpar Perform in the IDEAL Trial?

IDEAL is a randomized, double-blind, placebo-controlled phase 3 trial of 96 adults aged 18 to 75 years with PBC. Eligible patients had ALP above the ULN but below 1.67× ULN despite 12 months of ursodeoxycholic acid (UDCA), or were intolerant to UDCA. The Week 52 analysis included 65 participants on seladelpar and 31 on placebo.1

The primary objective compared ALP normalization at Week 52 between arms. Normalization was defined as a composite of ALP ≤1.0× ULN and a decrease of at least 15% from baseline. Seladelpar met this endpoint in 75.4% (49/65) of participants, compared with 16.1% (5/31) on placebo.1

The response came early. At one month, 52.3% of participants on seladelpar had reached ALP normalization, compared with 6.5% on placebo, and Gilead reported the response held through Week 52.1

What is the Safety Profile of Seladelpar in IDEAL?

According to Gilead, the safety profile of seladelpar in IDEAL was consistent with earlier studies, and no new safety concerns were identified. Adverse event incidence was generally similar between treatment arms. Serious adverse events occurred in 3.1% of participants on seladelpar and 12.9% of those on placebo, and none were considered related to study drug.1

Exploratory endpoints included other markers of cholestasis and liver injury, but the release did not give results for these measures. The IDEAL data have been accepted for publication in the Journal of Hepatology.1

The current US prescribing information includes a warning for fractures, which occurred in 4% of seladelpar-treated patients and no placebo-treated patients in earlier trials. It also warns of dose-related transaminase elevations above 3× ULN at daily doses of 50 mg and 200 mg; the recommended dose is 10 mg once daily. The most common adverse reactions include headache (8%), abdominal pain (7%), nausea (6%), abdominal distension (6%), and dizziness (5%).1

“The IDEAL study evaluated the impact of initiating second-line treatment in people living with PBC who have lower levels of baseline ALP elevation compared to prior clinical trials,” said Swati Tole, MD, MS, Senior Vice President, Clinical Development, Inflammation, Gilead Sciences.1 “A significantly greater proportion of people with elevated ALP levels, but below the threshold typically studied, achieved ALP normalization with Livdelzi, supporting ALP normalization as an achievable treatment goal. Together with the broader Livdelzi clinical program, IDEAL reinforces the importance of continuing to raise expectations for PBC care across a wide range of patients.”

Gilead stated it is discussing the IDEAL results with global regulatory authorities. Under its accelerated approval, seladelpar has not demonstrated a survival benefit or prevention of liver decompensation, and continued approval may depend on confirmatory trials.1

References

1. Gilead Sciences. 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 PBC. Published November 2026. Accessed November 5, 2026. https://www.gilead.com/news/news-details/2026/positive-phase-3-ideal-study-results-further-support-livdelzis-seladelpar-impact-on-achieving-alp-normalization-goals-in-second-line-treatment-across-a-broad-population-of-people-living-with

2. Hirschfield GM, Bowlus CL, Mayo MJ, et al. A phase 3 trial of seladelpar in primary biliary cholangitis. N Engl J Med. 2024;390(9):783-794. doi:10.1056/NEJMoa2312100