Gilead Sciences’ seladelpar gains support as PBC treatment in Europe

In a significant milestone for liver disease therapeutics, Gilead Sciences, Inc. has announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has delivered a positive recommendation for seladelpar, its oral therapy for primary biliary cholangitis (PBC). If approved by the European Commission, seladelpar could offer new hope to patients with this rare autoimmune liver condition, which has limited treatment options.

This decision, grounded in data from the pivotal RESPONSE trial, positions seladelpar as a second-line treatment for PBC, a condition that primarily affects women and can lead to significant liver damage if untreated. The EMA’s recommendation underscores seladelpar’s potential to address unmet medical needs, providing benefits such as alkaline phosphatase normalization, improved liver function, and relief from the burdensome symptom of chronic pruritus.

What Is Primary Biliary Cholangitis and Why Is It Hard to Treat?

Primary biliary cholangitis is a chronic autoimmune disease where the body mistakenly attacks the bile ducts in the liver. This leads to inflammation, scarring, and, eventually, liver failure if untreated. PBC is classified as a rare liver disease, affecting approximately 15 per 100,000 people in Europe, with a disproportionate impact on women.

Patients often present with symptoms such as fatigue, abdominal discomfort, and pruritus, a debilitating itch that severely affects quality of life. While the first-line treatment, ursodeoxycholic acid (UDCA), can slow disease progression, up to 40% of patients either do not respond to the therapy or cannot tolerate it due to side effects. For these individuals, finding effective second-line therapies has been challenging.

Seladelpar’s Clinical Trial Results: What Sets It Apart?

Gilead’s Phase 3 RESPONSE study evaluated the safety and efficacy of seladelpar as a second-line treatment for PBC. This double-blind, placebo-controlled trial enrolled 193 participants who either showed an inadequate response to UDCA or were unable to tolerate the treatment. Participants received a daily oral dose of 10 mg seladelpar or placebo for 12 months, with researchers tracking changes in key liver biomarkers and symptoms.

Seladelpar demonstrated significant clinical advantages. The trial found that:

62% of participants taking seladelpar achieved a composite biochemical response at 12 months, compared to 20% in the placebo group.

25% of seladelpar-treated participants experienced alkaline phosphatase normalization, a key indicator of reduced liver damage, compared to none in the placebo cohort.

Participants with moderate to severe pruritus saw a 3.2-point reduction on a 10-point scale, significantly greater than the 1.7-point reduction in the placebo group.

These results validate seladelpar’s ability to address both disease progression markers and quality-of-life symptoms, offering a dual benefit for patients with primary biliary cholangitis.

The Science Behind Seladelpar

Seladelpar is a PPAR-delta agonist, a first-in-class therapy that targets liver disease at a molecular level. PPAR-delta plays a critical role in regulating inflammation, bile acid metabolism, and fibrosis. Seladelpar’s anticholestatic, anti-inflammatory, antipruritic, and antifibrotic properties were validated in both preclinical and clinical trials, setting it apart from existing therapies.

Its ability to achieve alkaline phosphatase normalization is particularly noteworthy, as this biomarker predicts liver disease outcomes, including the risk of transplant or death. By addressing this marker while alleviating symptoms like pruritus, seladelpar demonstrates its potential as a comprehensive treatment for patients with PBC.

What the CHMP Recommendation Means

The CHMP’s positive opinion is a significant step toward seladelpar’s approval in the European Union. If the European Commission grants approval in early 2025, seladelpar will be indicated for use alongside UDCA in patients with an inadequate response to the therapy or as monotherapy in those unable to tolerate UDCA.

Seladelpar also holds Priority Medicine (PRIME) designation in the EU, which expedites the review process for therapies targeting conditions with unmet medical needs. This follows the drug’s accelerated FDA approval in the United States in August 2024 under the trade name Livdelzi®.

What Does This Mean for Patients?

For patients living with primary biliary cholangitis, the CHMP’s support of seladelpar brings hope for a better quality of life. Current therapies often fail to address symptoms like pruritus, which can leave patients feeling isolated and frustrated. Seladelpar’s potential to relieve itching while improving liver health could fill a critical gap in PBC management.

Dr. Palak Trivedi, a hepatologist at Queen Elizabeth Hospital, stated that seladelpar represents a breakthrough for PBC treatment by addressing both biochemical markers of the disease and the life-altering symptoms patients endure.

Regulatory Approvals and Next Steps

Gilead is actively pursuing regulatory approvals for seladelpar in other markets, including the United Kingdom, where the drug is under review by the Medicines and Healthcare products Regulatory Agency (MHRA). Continued FDA approval in the United States is contingent on long-term data from the ongoing AFFIRM study, which tracks outcomes in patients with compensated cirrhosis.

By prioritising clinical trial transparency and engaging with global regulatory bodies, Gilead aims to position seladelpar as a leading option for managing rare liver diseases.

A New Era for PBC Treatment

The development of seladelpar marks a new chapter for individuals living with primary biliary cholangitis. With its unique ability to address both alkaline phosphatase normalization and symptom relief, seladelpar offers a comprehensive solution for patients struggling with this rare liver disease.

As the European Commission prepares its decision, Gilead’s commitment to innovation in liver health continues to provide hope for patients and their families. If approved, seladelpar could redefine the standard of care for PBC, offering a brighter future for those who need it most.