CymaBay Therapeutics Announces Results From 52-Week, Open-Label, Phase 2 Study 

CymaBay Therapeutics, Inc. recently announced that results from the Phase 2, 52-week study of seladelpar in patients with primary biliary cholangitis (PBC) have been published in the Journal of Hepatology. https://doi.org/10.1016/j.jhep.2022.02.033.

This 52-week, Phase 2, dose-ranging, open-label study examined the efficacy and safety of seladelpar, a selective peroxisome proliferator-activated receptor-delta agonist, in adults with PBC who were receiving or intolerant to first-line therapy with ursodeoxycholic acid. Eligible patients were enrolled with a minimum serum alkaline phosphatase (ALP) levels of 1.67 times the upper-limit-of-normal (194 U/L) and which were on average in excess of 318 U/L. Seladelpar was administered orally once daily at 2 mg (n=11), 5 mg (n=53) or 10 mg (n=55) for 12 weeks, after which doses could be increased up to 10 mg if needed to improve treatment response. Cirrhosis was present in 21% of patients; 71% had pruritus.

An interim primary efficacy analysis of ALP change from baseline at Week 8 found that seladelpar treatment provided 26%, 33%, and 41% reductions for the 2 mg, 5 mg and 10 mg doses, respectively (all p<0.005). Responses were maintained or improved at Week 52 which included dose escalation in 91% and 80% of the 2 mg and 5 mg cohorts, respectively. At Week 52, the composite biochemical response (ALP <1.67×ULN, ≥15% ALP decrease from baseline, and normal total bilirubin) rates were 64%, 53%, and 67%, and ALP normalization rates were 9%, 13%, and 33% in the 2 mg, 5 mg, and 10 mg cohorts, respectively. The pruritus visual analog scale score was also decreased in the 5 mg and 10 mg cohorts. There were no treatment-related serious adverse events (AEs), and 4 patients discontinued due to AEs.

Lead investigator Professor Christopher Bowlus, MD, Division Chief of Gastroenterology and Hepatology at the University of California Davis Health, said “These results are particularly encouraging as they reveal a pattern of dose-dependent and persistent improvements in liver biochemistries which have been associated with improved clinical outcomes. Patients with PBC are in need of new therapies that are well tolerated and provide clinical benefits. These results support further development of seladelpar as a potential new therapy for PBC.”

A companion manuscript of results from this study were also published in the journal Liver International. It reported the effects of seladelpar treatment on patient reported symptoms of pruritus (itching), sleep and fatigue through one year of treatment: https://doi.org/10.1111/liv.15039.

Professor Andreas Kremer, MD, PhD, MHBA from the Department of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland served as the lead for analyzing the effects of seladelpar treatment on symptoms. Dr. Kremer offered that “Many patients with PBC have significant symptoms of itching, impaired sleep and fatigue, that can cause incessant suffering and result in great mental stress. Patients need therapies to address their symptoms and the results of this open label study suggest that seladelpar has the potential to provide symptom relief. The results reported in these two publications suggest a profile for seladelpar impacting both disease and symptoms, characteristics needed in new treatments for PBC.”

CymaBay is currently enrolling RESPONSE, a global Phase 3 study of seladelpar in patients with PBC that is intended to confirm these results. Seladelpar’s development program also includes ASSURE, a global Phase 3 long-term study that is expected to contribute safety and efficacy data on more than 300 patients treated with seladelpar.

PBC is a rare, chronic autoimmune 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.