Gilead Sciences recently released promising interim data from the Phase 3 ASSURE study on Livdelzi (seladelpar) for primary biliary cholangitis (PBC). The analysis, presented at The Liver Meeting® 2024, revealed that 81% of participants achieved a composite biochemical response after 30 months of treatment, indicating significant improvement in key measures of PBC progression. Furthermore, 41% of participants achieved normalized alkaline phosphatase (ALP) levels, a critical biomarker of liver function. No treatment-related serious adverse events were reported, and the overall safety profile remained robust. The incidence of adverse events also decreased over time, suggesting good tolerability with continued use. These results align with earlier findings presented at the European Association for the Study of the Liver (EASL) Congress.
The ASSURE study is an ongoing, open-label trial evaluating the long-term efficacy and safety of Livdelzi in adults with PBC who previously demonstrated an inadequate response or intolerance to ursodeoxycholic acid (UDCA). The interim analysis included participants from previous Livdelzi studies, including the pivotal Phase 3 RESPONSE study.
Gilead also presented additional analyses from the RESPONSE trial at the conference. These findings highlighted the drug’s positive impact on pruritus (itching), a common and often debilitating symptom of PBC. Livdelzi demonstrated statistically significant and durable improvements in both pruritus and markers of cholestasis, a condition where bile flow from the liver is reduced.
A separate analysis of a large safety database, encompassing up to five years of Livdelzi treatment, further reinforced the drug’s generally well-tolerated profile. The exposure-adjusted incidence of adverse events, serious adverse events, and liver-related adverse events were all lower for Livdelzi compared to placebo. No treatment-related serious adverse events were observed.
Livdelzi, a PPAR-delta agonist, works by regulating metabolic and liver disease pathways. Preclinical and clinical data suggest it possesses anticholestatic, anti-inflammatory, antipruritic, and antifibrotic properties. The drug received accelerated approval from the U.S. Food and Drug Administration (FDA) in August 2024 for treating PBC in combination with UDCA in adults with inadequate UDCA response or as monotherapy in UDCA-intolerant patients. This accelerated approval is based on ALP reduction; however, improvement in survival or prevention of liver decompensation has not yet been demonstrated. Continued approval hinges on verifying clinical benefits in confirmatory trials, including the already initiated AFFIRM study.
PBC, a chronic inflammatory liver disease predominantly affecting women, disrupts bile flow, leading to the accumulation of toxic bile acids within the liver. This causes inflammation, bile duct destruction, and elevated liver enzyme levels. Common symptoms include pruritus and fatigue, and the disease’s progression can increase the risk of liver-related mortality. Livdelzi represents a potential advancement in PBC treatment, offering a new option for patients who haven’t responded adequately to first-line therapies. Gilead is currently conducting further research, including the confirmatory AFFIRM study, to understand the long-term benefits of Livdelzi fully. The Gilead Support Path® Program provides resources for patients prescribed Livdelzi to navigate coverage and financial assistance options.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
