Gilead Sciences' Livdelzi (seladelpar) has demonstrated sustained efficacy and a favorable long-term safety profile in patients with primary biliary cholangitis (PBC), according to new data from a two-and-a-half-year interim analysis of the ongoing Phase 3 ASSURE study. The findings, presented at The Liver Meeting® 2024, highlight significant improvements in key measures of PBC progression.
Key Findings from the ASSURE Study
The ASSURE study (NCT03301506) is an open-label trial evaluating the long-term efficacy and safety of Livdelzi in adults with PBC who had an inadequate response or intolerance to ursodeoxycholic acid (UDCA). The interim analysis, with a data cutoff of January 31, 2024, included participants from prior Livdelzi clinical studies, including the pivotal Phase 3 RESPONSE study.
- Biochemical Response: 81% (30 out of 37) of participants treated with Livdelzi achieved a composite biochemical response (CBR) by Month 30.
- ALP Normalization: 41% (15 out of 37) of participants achieved normalization of alkaline phosphatase (ALP) levels.
- Safety Profile: The safety profile of Livdelzi remained robust, with no treatment-related serious adverse events (SAEs) reported. The exposure-adjusted incidence of adverse events decreased over time.
"These data support what we’ve already observed with seladelpar. The long-term data from the ASSURE study reinforce that seladelpar consistently lowers ALP, offering a promising and much-needed option for patients living with this chronic liver condition," said Eric J. Lawitz, MD, principal investigator and Medical Director of the Texas Liver Institute.
Additional Data from the RESPONSE Trial
Gilead also presented findings from two oral presentations highlighting additional analyses from the Phase 3 RESPONSE trial (NCT04620733):
- Subgroup Analysis in Cirrhosis Patients: A prespecified subgroup analysis underscored the efficacy and safety profile of Livdelzi in people living with PBC and compensated cirrhosis. At Month 12, participants with cirrhosis on Livdelzi showed a significant decrease in ALP compared to placebo.
- Pruritus Analysis: A secondary analysis of pruritus in RESPONSE showed that Livdelzi led to near resolution of itch at Month 12 in 26.5% and 18.8% of participants with a numerical rating score (NRS) of ≥4 and NRS ≥7 at baseline, respectively, versus 0% of participants on placebo.
Livdelzi's Impact on PBC Treatment
Livdelzi (seladelpar) is an oral PPAR-delta agonist approved for the treatment of PBC. It has demonstrated anticholestatic, anti-inflammatory, antipruritic, and antifibrotic effects in preclinical and clinical data. The drug received accelerated approval from the FDA in August 2024 and has also been accepted for review by regulatory agencies in the UK and Europe.
"Gilead has a legacy of bringing groundbreaking treatments to people in need and Livdelzi is the first and only treatment to demonstrate statistically significant and durable improvements in both pruritus and markers of cholestasis related to the risk of disease progression," said Timothy Watkins, MD, MSc, Vice President, Clinical Development, Inflammation Therapeutics, Gilead Sciences.
Ongoing Studies and Future Directions
Gilead has initiated a confirmatory long-term outcomes study called AFFIRM in people with compensated cirrhosis as part of the FDA's accelerated approval requirements. Continued approval for Livdelzi may be contingent upon verification of clinical benefit in this confirmatory trial.
About Primary Biliary Cholangitis (PBC)
PBC is a rare, chronic inflammatory liver disease affecting primarily women. It is characterized by impaired bile flow and the accumulation of toxic bile acids in the liver, leading to inflammation and destruction of bile ducts. The most common symptoms include pruritus and fatigue. Progression of PBC is associated with an increased risk of liver-related mortality.
