Investigational Seladelpar Demonstrates Significant Improvements in Liver Disease Progression and Reduced Itching in Primary Biliary Cholangitis

Gilead Sciences, Inc. (Nasdaq: GILD), following the recent acquisition of CymaBay Therapeutics, Inc., today announced interim results from the ongoing ASSURE study demonstrating treatment with seladelpar, an investigational PPAR delta agonist, led to improvements in markers of cholestasis and reduced inflammation. Additional findings demonstrate that seladelpar can help reduce pruritus (itch) in people living with primary biliary cholangitis (PBC). There are currently no treatments indicated to treat PBC-related pruritis. This data will be shared in an oral presentation during the Presidential Plenary of the Digestive Disease Week 2024 Conference in Washington, DC.

ASSURE is an open-label study evaluating the long-term safety and efficacy of seladelpar, a once daily potent and selective peroxisome proliferator-activated receptor (PPAR) delta agonist, or delpar. ASSURE enrolled adult patients with PBC who previously participated in a study of seladelpar where a key eligibility criterion included having an inadequate response or intolerance to ursodeoxycholic acid (UDCA). This interim data analysis did not include patients from the Phase 3 RESPONSE study, which will be reported separately. Of the 174 patients included, the majority had a gap of one year or more between completion of the respective primary study (seladelpar or placebo) and enrollment into ASSURE. Enrolled patients received an open-label oral dose of 10 mg seladelpar once daily, with the majority (97%) also receiving UDCA treatment.

Most patients enrolled in ASSURE were female (94%), with a mean age of 59 years. Baseline characteristics included mean alkaline phosphatase (ALP) 270.5 U/L and total bilirubin (TB) 0.75 mg/dL; 19% of enrolled patients met the criteria for cirrhosis. The study evaluated several prespecified biochemical endpoints, including the composite response of an alkaline phosphatase (ALP) below 1.67 x upper limit of normal (ULN), a decrease in ALP of at least 15%, and a total bilirubin (TB) below the ULN. Endpoints were evaluated over an interim observation period extending from enrollment through a data cutoff date of June 29, 2023, with the majority of those (85%) having at least 12 months of continuous treatment with seladelpar. Seventy percent of the 148 patients who completed 12 months of treatment achieved the clinically meaningful composite response endpoint. Among those receiving seladelpar, 37% experienced ALP normalization, with a mean ALP change from baseline of -44% (-144.4 U/L). Of the 20 patients who completed 24 months of treatment, 70% achieved the composite response endpoint and 25% experienced ALP normalization. Seladelpar also reduced other important biomarkers of liver injury including TB, gamma-glutamyl transferase (GGT) and alanine aminotransferase (ALT) levels by 9%, 36%, and 25% from baseline, respectively. There were no treatment-related serious adverse events in the study, as determined by the study investigators. Seladelpar was generally well tolerated, with discontinuation due to adverse events occurring in 4.6% of patients.