Seladelpar Linked to IL-31 Reduction and Itch Relief in PBC Phase 3 Analysis

In a groundbreaking study, CymaBay Therapeutics has unveiled the efficacy of seladelpar in reducing the levels of a specific cytokine, interleukin-31 (IL-31), which is linked to the alleviation of itching symptoms in patients with primary biliary cholangitis (PBC). This biopharmaceutical firm, dedicated to developing innovative treatments for liver and chronic diseases, has reported that seladelpar, an oral PPARδ agonist, has shown promising results in the Phase 3 ENHANCE trial.

The Phase 3 ENHANCE study conducted a post-hoc analysis where IL-31 serum levels were evaluated in PBC patients who were administered seladelpar at dosages of 5 mg and 10 mg daily, in comparison to a placebo group, over a period of three months. The cytokine IL-31 is known for its role in causing itching, and the study demonstrated a significant reduction in IL-31 levels in the seladelpar groups, with a 30% decrease in the 5 mg group and a substantial 52% decrease in the 10 mg group, contrasting with a 31% increase in the placebo group.

The study also found a correlation between IL-31 levels and the intensity of itching, measured using a numerical rating scale. Patients who showed an improvement in itching symptoms had a greater reduction in IL-31 levels. Additionally, baseline IL-31 levels were closely related to total and conjugated bile acids, and changes in IL-31 levels were strongly associated with changes in these bile acids in the seladelpar 10 mg group.

According to Professor Andreas Kremer, the lead author of the study and a hepatology expert, itching is a distressing symptom for many with PBC, and the study's findings are pivotal in understanding the mediators of cholestatic itch. He suggests that IL-31 could be a key factor driving itching in PBC patients and that these results could pave the way for new therapeutic approaches.

PBC is a rare chronic liver disease that predominantly affects women, characterized by poor bile flow and the buildup of harmful bile acids in the liver, leading to inflammation and bile duct destruction. Early symptoms include severe itching and fatigue, which can be debilitating. The progression of PBC increases the risk of liver-related mortality.

Seladelpar, the investigational treatment for PBC, is a novel PPARδ agonist that has the potential to regulate crucial metabolic and liver disease pathways. Preclinical and clinical data indicate that seladelpar can modulate genes involved in bile acid synthesis, inflammation, fibrosis, and lipid metabolism.

CymaBay Therapeutics is a clinical-stage company committed to enhancing the lives of those with liver and other chronic diseases through innovative therapies. Their deep insights into liver inflammation and fibrosis have led to seladelpar receiving significant recognition and status as a breakthrough therapy by the U.S. Food and Drug Administration, among other designations. The company's dedication to evidence-based decision-making and high-quality standards reflects its commitment to serving communities affected by these diseases.