Livdelzi lowers liver damage marker across PBC trials, data show
Treatment reduces levels of alkaline phosphatase in clinical trials
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Gilead Sciences‘ Livdelzi (seladelpar) effectively reduces blood levels of alkaline phosphatase (ALP), a key marker of liver damage, in most people with primary biliary cholangitis (PBC) who have higher-than-normal levels, according to new analyses from multiple clinical trials.
“Advancing and leading in liver disease requires a sustained commitment to addressing areas of persistent unmet need,” Swati Tole, MD, Gilead’s senior vice president of clinical development, said in a company press release. “As the field moves toward ALP normalization as an important treatment goal in PBC, we are focused on generating robust, clinically meaningful evidence to better understand treatment response and inform care—translating scientific progress into meaningful patient impact.”
PBC is marked by chronic inflammation of the bile ducts, a series of tubes that normally carry the digestive fluid bile out of the liver to the intestines. Inflammation blocks the normal flow through these tubes, leading to bile accumulation in the liver, damaging the organ and causing cholangitis symptoms such as itching.
The first-line PBC treatment is ursodeoxycholic acid (UDCA), which works to promote bile flow and is sold in the U.S. as Urso and Actigall. However, this therapy doesn’t work for everyone, and some people cannot tolerate its side effects.
Targeting protein
Livdelzi, sold as Lyvdelzi in Europe and Canada, is an oral medication that targets a protein involved in bile production, inflammation, and scarring, with the aim of reducing liver damage. It is widely approved as an add-on to UDCA in PBC patients for whom UDCA is ineffective, or for use on its own in patients who cannot tolerate UDCA.
The therapy’s approvals were mainly supported by data from Phase 3 clinical trials showing that up to one year of Livdelzi treatment was superior to a placebo at reducing liver damage markers and easing itching in adults with PBC who either didn’t respond to UDCA or couldn’t tolerate it.
Blood ALP levels are commonly used to track liver damage, and in PBC, levels above the upper limit of normal (ULN) are associated with a greater risk of death or requiring a liver transplant.
Gilead launched the Phase 3 IDEAL trial (NCT06060665) to test Livdelzi against a placebo in a subgroup of PBC patients with ALP levels in the range of 1 to 1.67 times the ULN, a population the company said has been historically underrepresented in trials “despite being commonly seen in clinical practice.” All 96 adult participants had shown an incomplete response to UDCA or were intolerant to it.
The company now announced that the study met its main goal, with a significantly higher proportion of Livdelzi-treated participants achieving composite ALP normalization — meaning ALP levels decreased by at least 15% and reached normal levels — relative to those on the placebo. The therapy’s safety profile was consistent with that observed in prior Livdelzi studies, with no new safety concerns identified.
Gilead didn’t give further specifics, noting that detailed results will be presented at an upcoming medical conference.
“IDEAL further strengthens support for the efficacy and safety profile of Livdelzi,” said Cynthia Levy, MD, associate director of the Schiff Center for Liver Diseases at the University of Miami. “These results extend the evidence base for Livdelzi to a broader population of people living with PBC and support ALP normalization as an achievable therapeutic goal in patients with ALP between 1 to 1.67 [times the ULN].”
Gilead also announced new, interim data from an ongoing Phase 3 study, ASSURE (NCT03301506), tracking long-term outcomes with Livdelzi in people with PBC who participated in previous trials of the therapy.
One analysis focused on the 50 participants who, prior to treatment, had ALP levels above the ULN but no higher than 1.67 times that limit. Data showed that 83% of participants achieved composite ALP normalization after one year and 74% after two years.
“Achieving ALP normalization is increasingly recognized as a key treatment goal in PBC due to its association with improved long‑term clinical outcomes,” Levy said in a separate press release from Gilead. “These data show that seladelpar can help people who have not reached ALP normalization achieve this important biochemical target and support its potential role across a broader range of people living with PBC, including those with lower ALP levels.”
Another analysis focused on the 91 participants who had a biochemical response after one year of Livdelzi treatment and who were followed for up to three years. A biochemical response was defined as ALP levels decreasing by at least 15% to below 1.67 times the ULN and a normalization of bilirubin, another liver damage marker.
Results showed that 85% of these patients demonstrated either stabilization or a reduction in liver stiffness measurements, used as a proxy for liver scarring.
“Combining ALP normalization with effective symptom management provides a more holistic approach to care,” Tole said. “With Livdelzi, we aim to address both—helping improve [itching], one of the most debilitating symptoms of PBC, and normalize ALP, a key marker of disease progression risk—supporting a comprehensive approach to disease management.”
