CymaBay Therapeutics Long-Term Open Label Study Finds Treatment With Seladelpar for 2 Years Improves Key Liver Biomarkers in Patients With PBC

CymaBay Therapeutics, Inc. recently announced that results of analyses from two clinical studies of seladelpar were delivered during The Liver Meeting Digital Experience 2021 (TLMdX) of the American Association for the Study of Liver Diseases (AASLD).

In an oral presentation titled Long-Term Safety and Efficacy of Seladelpar in Patients with Primary Biliary Cholangitis, Marlyn J. Mayo, MD, Professor and Liver Disease Specialist, University of Texas Southwestern Medical Center presented data from an open label, Long-Term Extension Study, highlighting the efficacy and safety of seladelpar at 1 and 2 years of treatment in patients with primary biliary cholangitis (PBC). Eligible PBC patients with either an inadequate response, defined as alkaline phosphatase (ALP) greater than or equal to 1.67 times the upper limit of normal (ULN), or intolerance to ursodeoxycholic acid (UDCA) were randomized to daily seladelpar 5 or 10 mg. The primary endpoint of this analysis was the percent change in ALP from baseline at 1 and 2 years. The mean percent change in ALP from baseline was -42% and -50% after 1 and 2 years, respectively. Key secondary endpoints of the analysis were a composite response of ALP <1.67x ULN, ALP decrease ≥15% and total bilirubin (TB) ≤ULN at 1 and 2 years; ALP normalization at 1 and 2 years and markers of hepatocellular injury. The composite endpoint was achieved by 64% and 79% of patients after one and two years, respectively. In addition, ALP normalization was achieved in 24% and 42% in patients at 1 and 2 years, respectively. In patients with elevated total bilirubin at baseline, 54% and 43% of patients achieved TB normalization at 1 and 2 years, respectively. Over 2 years, there were sustained reductions in ALT, AST, and GGT and platelet levels remained stable. Seladelpar appeared safe and well-tolerated. These data support that long-term treatment with seladelpar resulted in continued improvement in markers of cholestasis after 1 year.

Dr. Dennis Kim, Chief Medical Officer, said “These results are particularly encouraging as they suggest that seladelpar may provide an effective long-term treatment option for patients with PBC and may signal that the benefits gleaned may be sustained and perhaps even improve over a 2-year period.”

A second clinical presentation titled Efficacy and Safety of Seladelpar in Patients with Compensated Cirrhosis and Evidence of Portal Hypertension due to Primary Biliary Cholangitis was presented by Cynthia Levy, MD, Professor of Medicine, University of Miami. The results were from an electronic poster presentation of a pooled analysis of Phase 2 and Phase 3 studies (n=366) highlights the treatment effects of seladelpar in compensated cirrhotic patients with portal hypertension (n=22) after 3 months. In this analysis, 33% and 60% of cirrhotic patients with portal hypertension (PHT) met the composite responder endpoint in the 5 mg and 10 mg groups, respectively. ALP changes of -30% in the 5 mg and -45% in the 10 mg groups were observed and 8% and 40% of cirrhotic patients with PHT achieved ALP normalization in the 5 mg and 10 mg groups, respectively; corresponding changes at 5 and 10 mg in ALT levels were -13% and -26%, respectively. Total bilirubin, platelets, albumin, and INR either improved or remained stable. Seladelpar appeared safe and well-tolerated. Efficacy, safety, and tolerability in patients with compensated cirrhosis and PHT was comparable to that of non-cirrhotic patients.

“Patients with cirrhosis and portal hypertension have more narrow treatment options. Understanding the safety and efficacy of seladelpar in cirrhotic patients with and without portal hypertension will be an ongoing part of the seladelpar program with the goal of understanding if seladelpar is an appropriate treatment option for this currently underserved population,” said Dr. Kim. “We look forward to gathering additional data in cirrhotic and non-cirrhotic patients with PBC in RESPONSE, our Phase 3 global pivotal study of seladelpar, that is currently recruiting and enrolling patients.”

PBC is a rare, chronic inflammatory liver disease primarily affecting women (1 in 1,000) over the age of 40. PBC is characterized by impaired bile flow (known as cholestasis) and the accumulation of toxic bile acids in the liver, leading to inflammation and destruction of the bile ducts within the liver and causing increased levels of alkaline phosphatase (ALP) and total bilirubin. The most common early symptoms of PBC are itching (pruritus) and fatigue, which can be very debilitating for some patients. Progression of PBC is associated with an increased risk of liver cancer and liver-related mortality.

Seladelpar is a first-in-class oral, selective PPARδ agonist shown to regulate critical metabolic and liver disease pathways in indications with high unmet medical need. Preclinical and clinical data support its ability to regulate genes involved in bile acids synthesis, inflammation, fibrosis and lipid metabolism, storage and transport.

CymaBay Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on improving the lives of people with liver and other chronic diseases that have high unmet medical need through a pipeline of innovative therapies. Our deep understanding of the underlying mechanisms of liver inflammation and fibrosis, and the unique targets that play a role in their progression, have helped us receive breakthrough therapy designation (US FDA), PRIority MEdicines status (European Medicines Agency) and orphan drug status (US and Europe) for seladelpar, a first-in-class treatment for people with primary biliary cholangitis (PBC). Our evidence-based decision-making and commitment to the highest quality standards reflect our relentless dedication to the people, families and communities we serve. For more information, visit www.cymabay.com.