The groundbreaking seladelpar clinical trial results have shed new light on the treatment of PBC.
Seladelpar is a first-in-class oral, selective peroxisome proliferator-activated receptor (PPAR) delta agonist, or “delpar”. It has shown the ability to regulate critical metabolic and liver disease pathways. Preclinical and clinical data support its role in regulating genes involved in bile acid synthesis, inflammation, fibrosis, and lipid metabolism.
What is PBC?
Primary biliary cholangitis (PBC) is a rare and chronic inflammatory liver disease that primarily affects women. It is characterized by impaired bile flow, leading to the accumulation of toxic bile acids in the liver. One of the most debilitating symptoms of PBC is pruritus, or itching, which significantly impacts the quality of life for patients. Up until now, the underlying pathology of itch and effective treatment options have been limited.
Studies
One of the key findings from the Phase 3 ENHANCE study of seladelpar is the correlation between baseline intensity of patient-reported pruritus and higher levels of serum IL-31. IL-31 is a cytokine associated with itch, and its levels have been found to be elevated in patients with PBC. Professor Andreas E. Kremer, a leading authority in cholestatic pruritus, presented these findings, which were recognized with the International Award by the American College of Gastroenterology.
The data from the study showed that treatment with seladelpar resulted in significant decreases in both IL-31 levels and patient-reported itch. Patients who experienced clinically meaningful improvement in pruritus showed greater dose-dependent reductions in IL-31 from baseline than those without improvement. Furthermore, significant correlations were observed between changes in IL-31 and pruritus scores, alkaline phosphatase levels, and total bile acids. These results offer new insights into the underlying pathology of itch and provide hope for effective treatment options for patients with PBC.
Clinical Trials
In addition to the correlation between IL-31 levels and pruritus, a post-hoc analysis of four seladelpar clinical trials revealed the importance of liver biomarkers in predicting disease progression in PBC patients. The analysis focused on patients who had previously been treated with ursodeoxycholic acid (UDCA), the first-line therapy for PBC, but did not meet current clinical guidelines for second-line treatment.
Surprisingly, the analysis showed that even patients with any level of elevation in alkaline phosphatase (ALP), a key liver biomarker, had a significant risk of disease progression. These patients, who were not currently recommended by guidelines for second-line treatment, had elevated risk profiles based on Enhanced Liver Fibrosis (ELF) scores and liver stiffness measurements. This suggests that a broader patient group may benefit from earlier treatment to slow disease progression.
The correlation between serum IL-31 levels and pruritus provides insight into the underlying pathology of itch and offers hope for more effective therapies. Additionally, the analysis of liver biomarkers highlights the importance of early intervention to prevent disease progression. Seladelpar has the potential to revolutionize the management of PBC and improve the lives of patients suffering from this debilitating liver disease. As further research and development continue, the future looks promising for the treatment of PBC with seladelpar.
For more information on Primary Biliary Cholangitis and other gastrointestinal diseases click here, checkrare.com/diseases/gastrointestinal-diseases/
Reference