The European Commission (EC) has granted conditional marketing authorization to Gilead Sciences' seladelpar for the treatment of primary biliary cholangitis (PBC) in adults. This approval includes use in combination with ursodeoxycholic acid (UDCA) for patients who have an inadequate response to UDCA alone, or as a monotherapy for those unable to tolerate UDCA.
The decision follows a positive opinion from the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) in December 2024 and is primarily based on data from the Phase 3 RESPONSE trial. The final decision by the European Commission provides a new treatment option for individuals living with PBC in the EU.
Clinical Trial Data and Efficacy
The approval is supported by data from the pivotal Phase 3 RESPONSE study, a double-blind, placebo-controlled trial involving 193 participants across multiple sites worldwide. The study evaluated the efficacy and safety of seladelpar in adults with PBC who had shown inadequate response or intolerance to UDCA. Participants received a daily oral dose of 10 mg of seladelpar or placebo for 12 months.
The RESPONSE trial demonstrated that 62% of participants taking seladelpar achieved the primary endpoint of composite biochemical response at month 12, compared with 20% of participants taking placebo. A key secondary endpoint was the change from baseline pruritus score at month 6; treatment with seladelpar led to a statistically significant reduction in pruritus compared with placebo. Participants entering the study with moderate to severe itch experienced a 3.2-point improvement on a pruritus scale of 0-10 after six months of treatment with seladelpar, compared to a decrease of 1.7 points with placebo.
Normalization of alkaline phosphatase (ALP) values, an important marker of disease progression in PBC, was observed in 25% of trial participants at month 12 in the seladelpar group, while no participants in the placebo group experienced ALP normalization. According to Gilead, ALP is a cholestatic marker that is a predictor of risk for liver transplant and death.
Expert Commentary
"Today’s decision reinforces the clinical benefit and value of seladelpar and offers people living with PBC in Europe an important new treatment option," said María-Carlota Londoño, MD, PhD, a hepatologist at Hospital Clinic Barcelona. "There are people in Europe who do not have an adequate response to first-line therapy, and seladelpar helps address the unmet need for effective and symptom-directed treatment."
About Primary Biliary Cholangitis (PBC)
Primary biliary cholangitis (PBC) is a rare, chronic, autoimmune disease of the bile ducts that affects approximately 15 per 100,000 people in Europe, primarily women. PBC is characterized by impaired bile flow and the accumulation of toxic bile acids in the liver, leading to inflammation and destruction of the bile ducts, which can cause liver damage and possible liver failure if untreated. The most common symptoms of PBC are pruritus (chronic itch) and fatigue, which can be debilitating for some people. Progression of PBC is associated with an increased risk of liver-related mortality.
Seladelpar: A PPAR-delta Agonist
Seladelpar is an oral PPAR-delta agonist, or delpar, for the treatment of PBC. PPAR-delta has been shown to regulate critical metabolic and liver disease pathways. Preclinical and clinical data indicate seladelpar has anticholestatic, anti-inflammatory, antipruritic, and antifibrotic effects.
Regulatory Status and Future Studies
In addition to the European Commission's conditional marketing authorization, seladelpar was granted accelerated approval by the U.S. Food and Drug Administration (FDA) in August 2024 and has also received approval by the UK Medicines and Healthcare products Regulatory Agency (MHRA) in January 2025. Regulatory review is also underway in Canada and Australia. As part of the FDA accelerated approval, Gilead has committed to a confirmatory long-term outcomes study called AFFIRM, which has already been initiated in people with compensated cirrhosis. Continued U.S. approval may be contingent upon verification of clinical benefit in confirmatory trial(s).
