Gilead Sciences, Inc. (Nasdaq: GILD) recently announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion for the approval of seladelpar in treating primary biliary cholangitis (PBC). This treatment, which can be combined with ursodeoxycholic acid (UDCA) or used alone in patients unable to tolerate UDCA, is specifically for adults with PBC who have an inadequate response to UDCA. The European Commission is expected to make a final decision by the first quarter of 2025. This follows the U.S. FDA’s accelerated approval of seladelpar in August 2024.
PBC is a rare autoimmune disease that primarily affects women and can lead to severe liver damage and failure if left untreated. Common symptoms include pruritus (chronic itch) and fatigue, significantly impacting quality of life. The primary treatment goal is to suppress liver damage and alleviate symptoms, with a key biomarker for assessing disease progression being alkaline phosphatase (ALP) levels.
Seladelpar’s positive opinion was supported by data from the Phase 3 RESPONSE study, a pivotal clinical trial. The trial demonstrated that 62% of participants taking seladelpar achieved the primary endpoint of a composite biochemical response at 12 months, compared to only 20% in the placebo group. Additionally, 25% of patients receiving seladelpar saw their ALP levels normalize, a result not seen in the placebo group. As a secondary endpoint, treatment with seladelpar also significantly reduced pruritus, with participants experiencing a 3.2-point improvement on a pruritus scale, compared to 1.7 points in the placebo group.
Timothy Watkins, M.D., Vice President of Clinical Development at Gilead, expressed excitement about the CHMP’s recommendation, emphasizing Gilead’s commitment to improving both disease progression markers and symptom relief for people with PBC. The company is also working on regulatory submissions in other regions globally, with the FDA having granted accelerated approval for seladelpar in the U.S. earlier this year.
The RESPONSE study, which enrolled 193 participants, assessed seladelpar’s efficacy and safety as a second-line treatment for PBC patients who did not respond to UDCA. Patients were given 10 mg of seladelpar or placebo daily for 12 months, with primary outcomes focused on ALP levels and liver function tests.
PBC is an inflammatory liver disease where impaired bile flow leads to bile accumulation in the liver, causing liver damage. While no cure exists, treatments aim to control the disease and reduce symptoms. Pruritus and fatigue are the most common symptoms, often debilitating for patients.
Seladelpar, an oral PPAR-delta agonist, works by targeting liver disease pathways, offering multiple benefits, including anticholestatic, anti-inflammatory, antipruritic, and antifibrotic effects. It is the first treatment to show statistically significant improvements in biochemical responses and pruritus in PBC patients compared to a placebo.
In the U.S., seladelpar, marketed as Livdelzi, has been granted accelerated approval for PBC treatment in adults who either have an inadequate response to UDCA or cannot tolerate it. However, continued approval depends on confirmation of clinical benefit in ongoing trials.
In addition to the approval of seladelpar, Gilead continues to pursue innovative treatments for liver diseases. The company has a long-standing commitment to advancing therapies that improve the lives of people with chronic liver conditions such as hepatitis B, D, and PBC. With its groundbreaking research and collaborative efforts, Gilead aims to create a future without liver disease.
