Seladelpar demonstrates significant improvements in liver disease progression and reduced itching in primary biliary cholangitis

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 III 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.

“We are encouraged by these positive interim results from ASSURE, which are highly consistent with those observed in the Phase III, double-blind placebo-controlled RESPONSE study of seladelpar in people with an inadequate response or intolerance to UDCA,” said Cynthia Levy, M.D., Professor of Medicine, University of Miami and presenter of the study. “Seladelpar continues to demonstrate a significant impact on PBC disease in the liver, helps a significant proportion of patients achieve normalization of their ALP and importantly reduces pruritus, which is often a debilitating and unrelenting comorbidity. The safety and tolerability profile of seladelpar is consistent with previous studies in PBC and underscores its potential as a promising therapeutic option for people living with PBC.”

Patient-reported pruritus was monitored throughout the study using the numerical rating scale (NRS; 0-10). In the 60 patients with moderate-to-severe pruritus at baseline with an NRS score of ?4, a rapid improvement in pruritus was observed at Month 1. By Month 6 the patients reported a mean reduction of 3.5 points, and this impact was sustained through Month 12.

“The initial data from ASSURE further support the efficacy and safety profile of seladelpar observed across the robust development program and continue to indicate that seladelpar has the potential to be a best-in-class therapy that could help transform treatment for people living with primary biliary cholangitis,” said Merdad Parsey, Chief Medical Officer, Gilead Sciences. “The PBC community has been waiting for new treatments that help slow the progression of their liver disease as well as address difficult symptoms like pruritus that can have a significant impact on their quality of life. We are excited to offer a new option for this community as we work to bring seladelpar to people living with PBC, if approved.”

Additional results from ASSURE, including the long-term study of patients rolled over from RESPONSE to the ASSURE study, will be available at a future medical meeting.

ASSURE is an open label study to evaluate the long-term safety and tolerability of seladelpar in people with primary biliary cholangitis (PBC) who have already participated in other PBC clinical trials of seladelpar. The study is currently enrolling up to 500 people living with PBC from across 160 sites around the world. ASSURE will also address the long-term efficacy of seladelpar and its impact on important patient reported outcomes such as pruritus, or severe itch, which can have a significant impact on the quality of life of people living with PBC. Interim results of ASSURE (Session #2060), titled “Efficacy and Safety of Seladelpar in Patients with Primary Biliary Cholangitis in the ASSURE Study: Interim Results,” will be presented Dr. Cynthia Levy on behalf of the ASSURE Study investigators during the DDW 2024 Presidential Plenary on May 18, 2024, from 8:00 am to 9:30 am EDT.

A New Drug Application (NDA) for seladelpar for the treatment of PBC, including pruritus, in adults without cirrhosis or with compensated cirrhosis (Child Pugh A) who are inadequate responders or intolerant to UDCA, has been accepted for priority review by the FDA with an anticipated decision in August 2024. Seladelpar has also been accepted for review by the UK Medicines and Healthcare products Regulatory Agency (MHRA) and the European Medicines Agency (EMA).