Gilead's Seladelpar Shows Long-Term Efficacy and Safety in Primary Biliary Cholangitis

Gilead Sciences, after acquiring CymaBay Therapeutics, Inc., has announced promising two-year interim results from the ongoing ASSURE study examining seladelpar for primary biliary cholangitis (PBC), a rare, chronic liver disease. The recent findings, which were presented at the European Association for the Study of the Liver (EASL) Congress 2024 in Milan, Italy, show rapid and sustained improvements in cholestasis markers and significant reductions in pruritus (itching).

Study Insights and Key Findings

The ASSURE study, an open-label, long-term Phase 3 trial, seeks to evaluate the safety and efficacy of seladelpar, a potent and selective PPAR delta agonist, in adults with PBC. The current analysis included 179 participants from previous seladelpar studies and 158 from the Phase 3 RESPONSE study. Participants were administered 10 mg of seladelpar daily for up to 155 weeks. Results indicate that 70% of the 99 participants from legacy studies who completed 24 months of treatment met the composite response endpoint, which includes specific biochemical markers such as ALP and TB levels. Additionally, 42% of these participants achieved ALP normalization, a key indicator of liver disease progression.

For participants from the RESPONSE study, 62% of those who received seladelpar for 18 months and 72% for 24 months met the composite response endpoint. Moreover, among those who switched from placebo to seladelpar, 75% reached the composite response endpoint after six months of treatment, and 94% after 12 months. The safety profile of seladelpar was favorable, with no treatment-related serious adverse events reported.

Commentary from Medical Experts

Dr. Timothy Watkins, Vice President of Clinical Development of Inflammation Therapeutics at Gilead Sciences, highlighted the potential of seladelpar as a best-in-class therapy for PBC. He emphasized its ability to normalize liver function markers and significantly reduce pruritus, a debilitating symptom that affects the quality of life for people with PBC.

Dr. Palak Trivedi, a hepatologist and presenter at EASL, pointed out the long-term efficacy and safety of seladelpar, noting the meaningful reduction and normalization of liver blood tests and the decrease in itch intensity. He emphasized the unmet needs in PBC treatment, with about 40% of patients not achieving desired outcomes with current therapies.

Sub-Study of Participants with Cirrhosis

Results from a subset of ASSURE participants with compensated cirrhosis showed clinically meaningful improvements in markers of cholestasis and liver injury. Out of 32 participants with compensated cirrhosis who completed 12 months of treatment, 56% met the composite biochemical endpoint, and 47% achieved ALP normalization.

Regulatory Status

A New Drug Application (NDA) for seladelpar for PBC treatment has been accepted for priority review by the U.S. Food and Drug Administration (FDA), with a decision expected in August 2024. The U.K. Medicines and Healthcare Products Regulatory Agency (MHRA) and the European Medicines Agency (EMA) have also accepted seladelpar for review.

About the ASSURE Study

The ASSURE study aims to evaluate the long-term safety and tolerability of seladelpar in PBC patients who have participated in previous seladelpar trials. It is currently enrolling up to 500 participants worldwide. The study will also assess the long-term efficacy of seladelpar and its impact on patient-reported outcomes such as cholestatic pruritus.

About Seladelpar

Seladelpar is an investigational treatment for PBC and a selective PPAR-delta agonist. It regulates critical metabolic and liver disease pathways and has shown potential in preclinical and clinical studies. Seladelpar is not yet approved by the FDA or other regulatory agencies.

About PBC

Primary biliary cholangitis (PBC) is a rare, chronic inflammatory liver disease that primarily affects women. It is characterized by impaired bile flow and the accumulation of toxic bile acids in the liver, leading to inflammation and damage to the bile ducts. PBC's early symptoms include pruritus and fatigue, which can significantly impact quality of life.

About Gilead Sciences

Gilead Sciences, Inc. is a biopharmaceutical company dedicated to creating innovative medicines for life-threatening diseases. With a history of breakthroughs in treatments for HIV, hepatitis, cancer, and inflammation, Gilead operates in over 35 countries and aims to improve the lives of people worldwide.

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