Gilead Sciences' Livdelzi® (seladelpar) has demonstrated sustained efficacy and a favorable long-term safety profile in patients with primary biliary cholangitis (PBC), according to interim data from the ongoing Phase 3 ASSURE study. The findings, presented at The Liver Meeting® 2024, highlight Livdelzi's potential as a valuable treatment option for individuals with PBC who have an inadequate response or intolerance to ursodeoxycholic acid (UDCA).
Sustained Biochemical Response and ALP Normalization
The ASSURE study, an open-label trial evaluating the long-term safety and efficacy of Livdelzi, revealed that 81% (30 out of 37) of participants achieved a composite biochemical response (CBR) by month 30. This CBR indicates significant improvements in key measures of PBC progression. Furthermore, 41% (15 out of 37) of participants experienced normalization of alkaline phosphatase (ALP) levels, a critical biomarker of liver function.
Eric J. Lawitz, MD, principal investigator and Medical Director of the Texas Liver Institute, emphasized the importance of ALP levels in assessing liver health, stating, "ALP levels are recognized as an important surrogate marker of disease progression in PBC, and providers are shifting to view ALP normalization as a treatment goal... reducing, or even normalizing these levels, can make a significant difference in the management of this disease."
Pruritus Relief and Safety Profile
In addition to biochemical improvements, Livdelzi demonstrated a notable impact on pruritus, a common and debilitating symptom of PBC. A secondary analysis of the Phase 3 RESPONSE trial showed that Livdelzi led to near resolution (NRS of 0 or 1) 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. The safety profile of Livdelzi remained robust, with no treatment-related serious adverse events (SAEs) reported throughout the study duration. The exposure-adjusted incidence of adverse events decreased over time, with 86, 70, and 63 participants per 100 patient-years observed in years 1, 2 and 3 of treatment, respectively.
Additional Findings from the RESPONSE Trial
Gilead also presented findings from two oral presentations highlighting additional analyses from the Phase 3 RESPONSE trial:
- A prespecified subgroup analysis underscored the efficacy and safety profile of Livdelzi in people living with PBC and compensated cirrhosis. At Month 12, the adjusted mean change from baseline in ALP for participants with cirrhosis on Livdelzi was -121.4 U/L (a decrease of approximately 35% from baseline) versus 23.2 U/L (an increase of approximately 6.6%) on placebo.
- A secondary analysis of pruritus in RESPONSE showed that among participants with a numerical rating score (NRS) of ≥4 and NRS ≥7 at baseline, Livdelzi led to near resolution (NRS of 0 or 1) of itch at Month 12 in 26.5% and 18.8% of participants, respectively, versus 0% of participants on placebo.
Livdelzi's Role in PBC Treatment
Livdelzi (seladelpar) is an oral PPAR-delta agonist approved for the treatment of PBC in combination with UDCA in adults who have had an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA. The drug received accelerated approval from the FDA in August 2024 based on a reduction in ALP. Continued approval may be contingent upon verification of clinical benefit in confirmatory trials. The ASSURE trial is ongoing and enrolling up to 500 participants with PBC from across 160 sites around the world.
