NEJM Reports Favorable Seladelpar Phase 3 Results in PBC Treatment

CymaBay Therapeutics' seladelpar has shown promising results in treating primary biliary cholangitis (PBC), according to a study published in The New England Journal of Medicine. The Phase 3 RESPONSE trial demonstrated that seladelpar, a selective peroxisome proliferator-activated receptor delta (PPARδ) agonist, effectively reduced cholestasis and liver injury in patients with PBC. The drug also provided significant relief from pruritus, a severe itching symptom that affects the quality of life for PBC patients.

The double-blind, placebo-controlled study involved 193 participants with PBC who were randomized to receive either seladelpar 10 mg or a placebo daily for one year. The trial's primary endpoint focused on the normalization of alkaline phosphatase (ALP) and total bilirubin levels at 12 months. Seladelpar achieved this endpoint in 61.7% of the treated group, compared to only 20.0% in the placebo group, marking a statistically significant improvement.

Dr. Gideon Hirschfield, an expert in autoimmune liver disease research, highlighted the significance of the RESPONSE data, emphasizing the need for potent, effective, and safe treatment options for PBC, a chronic autoimmune condition. The study showed that seladelpar not only improved liver function but also significantly reduced itching, a common and debilitating symptom of PBC.

Secondary endpoints revealed that seladelpar led to a 25.0% normalization rate of ALP levels, compared to none in the placebo group. The drug also outperformed the placebo in reducing alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) levels. Patient-reported pruritus was measured using a numerical rating scale, and seladelpar demonstrated a significant reduction in itching as early as the fourth week, with improvements sustained up to 12 months.

Safety profiles of seladelpar were comparable to those of the placebo group, with the most common adverse events being COVID-19 and pruritus. Serious adverse events were reported in a small percentage of patients in both groups, with no events attributed to seladelpar.

Charles McWherter, Ph.D., CymaBay's Chief Scientific Officer, underscored the importance of the publication, recognizing the potential of seladelpar to transform PBC treatment. The FDA has accepted a New Drug Application for seladelpar, granting it priority review, and CymaBay plans to file for marketing authorization in the EU and UK in the first half of 2024.

PBC is a rare, chronic liver disease that predominantly affects women and is characterized by impaired bile flow and the accumulation of toxic bile acids in the liver. The disease's progression increases the risk of liver-related mortality. Seladelpar, as a first-in-class PPARδ agonist, has the potential to address the high unmet medical need in treating PBC by regulating key metabolic and liver disease pathways.

CymaBay Therapeutics is a clinical-stage biopharmaceutical company dedicated to improving the lives of those with liver and other chronic diseases. The company's commitment to evidence-based decision-making and adherence to high-quality standards reflects its dedication to serving patients, families, and communities affected by chronic conditions.