MILAN — according to two interim analyses of the ASSURE long-term extension study.
The first analysis of 337 patients with PBC, with and without cirrhosis, showed that treatment with seladelpar had a durable effect up to 2 years on cholestasis and markers of liver injury, as well as a sustained reduction in pruritus, Palak Trivedi, MD, associate professor at the National Institute for Health Research Birmingham Biomedical Research Centre, University of Birmingham, Birmingham, England, reported in a poster presented at the European Association for the Study of the Liver (EASL) Congress 2024.
The 2-year analysis also showed that seladelpar, a first-in-class, orally active agent, was safe and well tolerated in this patient population, he added.
These “results are consistent with the pivotal phase 3 RESPONSE study,” Dr. Trivedi noted. The RESPONSE study showed that seladelpar significantly improved liver biomarkers of disease activity and symptoms of pruritus at 12 months in patients with PBC who had an inadequate response or intolerance to ursodeoxycholic acid (UDCA), the standard of care, and had no history of hepatic decompensation. Patients with cirrhosis were allowed to enroll.
A total of 158 patients from the RESPONSE trial, both from the placebo and from the active treatment arm, were rolled over into the ASSURE trial. Another subset of 179 patients were drawn from prior seladelpar placebo-controlled studies (referred to as “legacy studies”), including the ENHANCE study. All participants in the current analysis received 10 mg of seladelpar, once daily, for up to 155 weeks.
Of the participants from the legacy studies, 99 completed 24 months of treatment with seladelpar, and 164 completed 12 months of treatment. In the 24-month treatment group, 70% met the composite response endpoint, which included alkaline phosphatase (ALP) levels below 1.67 times the upper limit of normal, a decrease in ALP levels of at least 15%, and total bilirubin levels at or below the upper limit of normal, according to a press release of the study findings. In addition, 42% of these participants achieved ALP normalization at 24 months, a marker of liver disease progression. In the 12-month treatment group, 73% achieved the clinically meaningful composite response endpoint, with 42% experiencing ALP normalization.
For patients rolled over from RESPONSE, 102 received 18 months of treatment with seladelpar, and 29 received 24 months of treatment. A total of 62% of patients in the 18-month group achieved the composite endpoint, and 33% achieved ALP normalization, while 72% of the 24-month group reached the composite endpoint, and 17% had ALP normalization.
Of patients who had received a placebo in the RESPONSE trial and went on to receive treatment with seladelpar, 75% achieved the composite endpoint, 27% had ALP normalization at 6 months, and 94% achieved the composite endpoint and 50% reached ALP normalization at 12 months.
Key secondary endpoints included ALP normalization and changes in liver enzymes (ALP, total bilirubin, gamma-glutamyl transferase [GGT], alanine transaminase [ALT], and aspartate aminotransferase [AST]).