Seladelpar granted conditional European Marketing Authorization for the treatment of primary biliary cholangitis – Gilead Sciences

Gilead Sciences Inc. announced that the European Commission (EC) has granted conditional marketing authorization for seladelpar for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults who have an inadequate response to UDCA alone, or as monotherapy in those unable to tolerate UDCA. Seladelpar (an orphan designated product) is now approved and will provide an important treatment option for people living with the rare liver disease in the European Economic Area (EEA).

“The decision reinforces the clinical benefit and value of seladelpar and offers people living with PBC in Europe an important new treatment option,” said Dr.. María-Carlota Londoño, 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.”

The EC’s decision follows the positive opinion of the Committee for Medicinal Products for Human Use (CHMP) of the EMA in December 2024, and is primarily based on results from the pivotal placebo-controlled Phase III RESPONSE study. In the study, 62% of participants taking seladelpar achieved the primary endpoint of composite biochemical response at Month 12, versus 20% of participants taking placebo. Treatment with seladelpar led to normalization of ALP values in 25% of trial participants at Month 12. This change was not seen in any trial participants receiving placebo. Change from baseline pruritus score at Month 6 was a key secondary endpoint; patients treated with seladelpar demonstrated a statistically significant reduction in pruritus compared with placebo. After six months of treatment with seladelpar, participants entering the study with moderate to severe itch experienced a 3.2-point improvement on a pruritus numerical rating scale of 0-10, a clinically meaningful improvement, compared to a decrease of 1.7 points with placebo. There were no treatment-related serious adverse events, as determined by study investigators. The most common adverse events, occurring in ≥ 5% of participants in the seladelpar arm and at an incidence of ≥ 1% higher than in the placebo arm were headache, nausea, abdominal pain, and abdominal distension.

Gilead is now working with health authorities across Europe to ensure people living with PBC who are eligible for seladelpar have access as soon as possible. Seladelpar has been granted conditional marketing authorization in the EU. Continued authorization of seladelpar for the approved indication will be contingent on verification and description of clinical benefit in confirmatory trial(s).

RESPONSE is a Phase III, double-blind, placebo-controlled clinical trial (NCT04620733) designed to evaluate the efficacy and safety of seladelpar in adults with PBC who have shown inadequate response or intolerance to first-line treatment with UDCA. The trial enrolled 193 participants across multiple sites worldwide. RESPONSE assessed key biomarkers of cholestasis, including ALP levels, as well as secondary endpoints related to liver function and patient quality of life.

Participants in the RESPONSE trial received a daily oral dose of 10 mg of seladelpar or placebo for 12 months, with a focus on measuring changes in ALP and other relevant liver function tests. The trial aimed to address the high unmet need for effective second-line therapies for individuals with PBC, providing important insights into the long-term management of this chronic liver disease.

“People living with PBC in Europe have been waiting for treatment advancements for many years. Up until now, there has been no approved treatment for PBC addressing both the surrogate biomarkers for underlying disease and pruritus, a common and at times debilitating symptom of PBC. That changes  with the conditional approval of seladelpar, which has been shown to both help treat the disease and reduce pruritus,” said Dr. Timothy Watkins,  Vice President, Clinical Development of Inflammation Therapeutics, Gilead Sciences. “We look forward to working with health authorities across Europe to bring this promising new treatment to all those who could benefit.”