Livdelzi maintains benefits for up to 3 years in PBC: Phase 3 data
Medication shown to stabilize or reduce itching, liver stiffness in adults
Up to three years of treatment with Gilead Sciences‘ Livdelzi (seladelpar) results in sustained reductions in itching and biomarkers of liver injury in adults with primary biliary cholangitis (PBC). It also stabilized or reduced liver stiffness, a marker of liver scarring.
That’s according to interim data from the long-term Phase 3 ASSURE clinical trial (NCT03301506), which were presented at The Liver Meeting hosted by the American Association for the Study of Liver Diseases, held Nov. 7-11 in Washington, D.C.
“Patients treated with Livdelzi for up to 3 years demonstrated stability or improvement in liver stiffness, with the greatest benefit observed in those at highest risk,” Dietmar Berger, MD, PhD, chief medical officer at Gilead, said in a company press release. “These data … underscore Livdelzi’s potential to meaningfully alter the trajectory of PBC by addressing liver stiffness, a key marker of disease progression.”
Treatment options for PBC patients limited after Ocaliva withdrawals
At the meeting, Gilead also shared real-world data showing similar reductions in alkaline phosphatase (ALP), a biomarker of liver damage, in PBC patients treated with Livdelzi as a second-line therapy and those who switched from the second-line therapy Ocaliva (obeticholic acid) to Livdelzi.
Ocaliva was recently withdrawn from the U.S. and European markets due to safety concerns, limiting treatment options for PBC patients who can’t tolerate or don’t adequately respond to the first-line PBC therapy ursodeoxycholic acid (UDCA).
“The withdrawal of [Ocaliva] acid has created a need for patients with PBC who had not responded adequately to ursodeoxycholic acid and were being treated with [Ocaliva],” Christopher L. Bowlus, MD, a professor at the University of California Davis School of Medicine, said in an emailed statement to Liver Disease News. “Our real-world data on [Livdelzi] are encouraging — confirming its safety as well as effectiveness.”
Bowlus, who was involved in the real-world study and ASSURE’s liver stiffness analyses, added: “In addition, these results support the use of [Livdelzi] as an effective option for patients who previously relied on [Ocaliva] to ensure continuity of care for our patients in need of second-line agents,.”
Livdelzi designed to reduce liver damage by activating key protein
In PBC, inflammation of the tubes that carry bile, a digestive fluid produced by the liver, blocks the normal flow of bile. This backup can damage the liver and allow bile to enter the bloodstream, leading to symptoms such as itching, also known as pruritus.
Livdelzi, sold as Lyvdelzi in Europe and Canada, is an oral therapy designed to reduce liver damage by activating PPAR-delta, a protein involved in bile production, inflammation, and scarring.
It’s approved in the U.S., Europe, and Canada for adults with PBC who are unresponsive or intolerant to UDCA, which is sold in the U.S. as Urso and Actigall, as well as generics.
ASSURE is an ongoing study evaluating the long-term outcomes of Livdelzi treatment in PBC patients who completed earlier trials testing the drug. Newly presented data concerned biochemical responses, itching, and liver stiffness outcomes after up to three years of treatment.
Of the 337 ASSURE participants on Livdelzi’s approved daily dose of 10 mg, 76.6% had been treated with Livdelzi for at least two years, and 34.7% for at least three years.
More than two-thirds of participants achieved a composite biochemical response (CBR) at one year (69.2%), two years (70.2%), and three years (67.2%). CBR was defined as blood ALP levels of less than 1.67 times the upper limit of normal, with at least a 15% drop from the trial’s start, and a normalization of the liver damage marker bilirubin.
Livdelzi led to rapid reductions in ALP levels from week one, and these were sustained for up to three years. Normalization of both ALP and bilirubin was observed in more than one-third of patients after one year (34.5%), two years (35.7%), and three years (36.8%).
‘No new safety concerns identified with up to 4 years of treatment’
The pruritus analysis included patients with moderate to severe itch at the time of enrollment in the previous Phase 3 RESPONSE trial (NCT04620733). The reduced itching among Livdelzi-treated patients in RESPONSE was maintained in ASSURE for at least up to 30 months, or about 2.5 years. A clinically meaningful reduction in itching was also reported by more than half of patients who switched from placebo to Livdelzi in ASSURE.
The liver stiffness analysis, as assessed by FibroScan, included 311 participants from the ASSURE study. For most (85%), their liver stiffness measurements (LSMs) were either stable or reduced, indicating less liver scarring, after three years of treatment.
Researchers divided patients into risk-progression groups based on the degree of pre-Livdelzi liver stiffness. They found that LSMs decreased by 2% for those with a mild risk, 7.4% for moderate-risk patients, and 29.7% for those with a high risk.
Further analyses showed that younger age and higher ALP levels at Livdelzi initiation were each significantly associated with a higher chance of a greater than 30% increase in LSMs after three years.
These real-world findings offer encouraging evidence that [Livdelzi] is a viable alternative to [Ocaliva] and promising second-line therapy for patients with PBC.
Safety data showed that the therapy was generally safe and well-tolerated, “with no new safety concerns identified with up to 4 years of treatment,” the researchers wrote.
The real-world analysis included 266 patients with PBC who used Livdelzi as second-line therapy, either in combination with UDCA or alone, and 130 patients who switched from Ocaliva to Livdelzi. Data was analyzed through HealthVerity claims in the U.S. between August 2023 and June 2025.
ALP levels dropped in both groups, and the proportion of patients reaching levels below 1.67 times the upper limit of normal increased from 52.5% to 74.5% in the Livdelzi initiation group and from 54.8% to 83.3% in the Ocaliva-Livdelzi switch group.
Nearly all (93%) patients continued Livdelzi treatment throughout the observation period, and safety labs “were generally similar before and after [Livdelzi] initiation in both groups,” the researchers wrote.
“These real-world findings offer encouraging evidence that [Livdelzi] is a viable alternative to [Ocaliva] and promising second-line therapy for patients with PBC,” Bowlus said in the press release.
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