Two-and-a-half-year interim analysis from the ongoing Phase III ASSURE study, showed that 81% of participants with primary biliary cholangitis treated with Livdelzi (seladelpar) achieved a composite biochemical response

These findings were unveiled as a late-breaker presentation at The Liver Meeting 2024 hosted by the American Association for the Study of Liver Diseases (AASLD) in San Diego, California from November 15-19.

ASSURE (NCT03301506) is an ongoing, open-label, study evaluating the long-term efficacy and safety of Livdelzi. ASSURE is enrolling adults with PBC who previously participated in a study of Livdelzi where a key eligibility criterion includes having an inadequate response or intolerance to ursodeoxycholic acid (UDCA). Using a data cutoff of January 31, 2024, the interim analysis represented all participants in the ASSURE study, including those who participated in prior clinical studies of Livdelzi (legacy studies) and participants from the pivotal Phase III  RESPONSE study. Results demonstrate the safety profile of Livdelzi remains 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. Livdelzi continues to appear generally well tolerated, with no new safety signals or change in frequency of adverse events (AEs) with up to three years of exposure. These results are consistent with the results presented at the European Association for the Study of the Liver (EASL) Congress earlier this year.

“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 and a Clinical Professor of Medicine at University of Texas Health San Antonio, Texas, USA. “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. ALP levels are critical markers in assessing liver health, and for people with PBC who are not adequately responding to first-line therapies, reducing, or even normalizing these levels, can make a significant difference in the management of this disease.”

In addition to the ASSURE data, Gilead showcased findings from two oral presentations highlighting additional analyses from the Phase III RESPONSE trial (NCT04620733):

• 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, and -134.8 U/L (a decrease of approximately 43.5%) for Livdelzi versus -18.0 U/L (a decrease of approximately 5.8%) for placebo in participants without cirrhosis. In Livdelzi participants, AEs were reported in 89% and 86% of participants with and without cirrhosis, respectively, versus 89% and 84% in placebo participants.
• 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. In Livdelzi participants, AEs were reported in 87.8% and 86.1% of participants with baseline NRS ≥4 and NRS <4, respectively, versus 91.3% and 81% in placebo participants. Overall, the proportion of participants with AEs was similar for Livdelzi and placebo regardless of baseline itch severity.

In a separate analysis, which spans the Livdelzi program in PBC, Gilead highlighted findings from a large safety database of people treated with Livdelzi for up to five years, which demonstrated that Livdelzi was generally well tolerated considering cumulative use across studies. A total of 486 participants received Livdelzi 10 mg and 152 participants received placebo. The exposure-adjusted subject incidence (per 100 patient-years) for Livdelzi was 48.3 for AEs, 8.0 for SAEs, and 6.1 for liver-related AEs, as compared to 132 for AEs (rate reflective of shorter exposure time for placebo participants), 7.8 for SAEs, and 13.3 for liver-related AEs in placebo participants. There were no treatment-related SAEs.