NEWARK, Calif., May 20, 2019 (GLOBE NEWSWIRE) — CymaBay Therapeutics, Inc. (NASDAQ: CBAY), a biopharmaceutical company focused on developing and providing access to innovative therapies for patients with liver and other chronic diseases, today announced results related to its seladelpar clinical development program for the treatment of primary biliary cholangitis (PBC). These data were presented today at Digestive Disease Week® (DDW) in San Diego, California. Seladelpar is a potent and selective peroxisome proliferator-activated receptor delta (PPARδ) agonist currently in development for PBC and nonalcoholic steatohepatitis (NASH).
A poster presentation titled “Capturing the experience and impact of itch in patients with primary biliary cholangitis (PBC),” highlighted results from a qualitative study designed to understand the experience and impact of itch on PBC patients and to examine the validity of three existing pruritus patient-reported outcome (PRO) measures (Itch Numeric Rating Scale (NRS), 5-D Itch Scale, and the Itch Visual Analogue Scale (VAS)). A total of 12 PBC patients with a score ≥4 on the Itch NRS (0-10) were interviewed which involved completing the three PRO measures and describing their PBC itch experience. All participants reported receiving medication to manage their PBC. Most participants described their PBC severity as “moderate,” “moderate and severe,” or “severe.” Fifty percent of participants reported experiencing PBC-related itch a few times a day and generally described their itch as feeling like something crawling under the skin, having an involuntary reaction to scratch, or a tingling or creepy sensation that often wasn’t relieved with scratching. The most commonly reported impacts from itch were on sleeping, daily activities, and social functioning from scratching in public or having sores on skin. Participants considered the Itch NRS, 5-D Itch, and Itch VAS relevant instruments for assessing itch and found that a 3- to 5-point reduction in the Itch NRS score (>66.7%) and a 5- to 55-point (average -30 points) reduction in the Itch VAS (100%) reflect a meaningful change in treatment effectiveness.
“While ‘itch’ may sound like a benign disease symptom, these new study results show that it can have significant negative effects on PBC patients,” said Cathy Mumford, a PBC patient and member of the Executive Committee of PBCers Organization, an advocacy group offering support and education to PBC patients and their families and raising funds to support PBC research and discover a cure for the disease. “As I know from my own experience and the experiences of the patients we serve, evaluating the potential of new treatment options to improve aspects of patient quality of life, such as itch, are critical to improving the long-term management of PBC.”
“Itch (pruritus) has been one of the most common complaints amongst PBC patients, occurring in 20% to 70% of PBC patients,”1 said Dr. Pol Boudes, Chief Medical Officer of CymaBay Therapeutics. “We are honored to collaborate with the PBCers Organization, the Canadian PBC Society, and Evidera and to share data that highlight the experience and relevance of itch from the patient perspective. We recognize that effectively managing PBC-related itch is important for improving quality of life for PBC patients, and are evaluating the effects of seladelpar on this important symptom in ENHANCE, our ongoing global Phase 3 registration study of seladelpar in PBC patients.”
Encore Data Presentations
Data previously presented at The International Liver Congress™ in April 2019 were also presented in two posters at DDW:
“Seladelpar for the treatment of primary biliary cholangitis: experience with 25 cirrhotic patients”
This poster reported the results of a subset of patients with compensated cirrhosis (Child-Pugh A) from an ongoing Phase 2 study designed to assess the safety and efficacy of seladelpar at a daily dose of 5 mg or 10 mg in PBC patients who had an inadequate response (alkaline phosphatase [AP] ≥ 1.67 x upper limit of normal [ULN]) or an intolerance to ursodiol and a total bilirubin ≤ 2 mg/dL. Cirrhosis was diagnosed using liver biopsy, liver elastography, or liver imaging. Patients initiated on 5 mg could be dose-escalated to 10 mg after 12 weeks of treatment if it was tolerated and AP threshold criterion was not met (5/10 mg group). The primary outcome was percent change from baseline in AP. Secondary outcome measures included ALT, total bilirubin, and pruritus using the visual analogue scale (VAS). At 52 weeks in patients with cirrhosis, mean relative decreases in AP were -36% and -43% in the 5/10 mg and 10 mg group, respectively. Treatment with seladelpar also demonstrated robust anti-inflammatory activity with a decrease in ALT comparable to what was observed in non-cirrhotic patients. Total bilirubin remained stable throughout 52 weeks. Seladelpar was well tolerated and appeared safe. Three patients with cirrhosis experienced an SAE, all unrelated to seladelpar. Total bilirubin, platelets, albumin, and INR remained stable. No liver decompensation events were observed. There was no transaminase safety signal, and importantly, seladelpar treatment was not associated with drug-induced pruritus or hepatotoxicity.
“Pharmacokinetics, safety, and tolerability of seladelpar in subjects with hepatic impairment”
Data in this poster demonstrated that single dose oral administration of seladelpar was well tolerated and appeared safe in subjects with varying degrees of hepatic impairment (Child-Pugh A-C) and thus provided important information on seladelpar pharmacokinetic exposure and implications for dosing in this challenging population.
CymaBay’s presentations from Digestive Disease Week® 2019 can be found at: https://ir.cymabay.com/presentations.
Primary biliary cholangitis (PBC) is a serious and potentially life-threatening autoimmune disease of the liver characterized by impaired bile flow (cholestasis) and accumulation of toxic bile acids. There is an accompanying inflammation and destruction of the intrahepatic bile ducts, which can progress to fibrosis, cirrhosis and liver failure. Other clinical symptoms of PBC include fatigue and pruritus, which can be quite disabling in some patients. PBC is primarily a disease of women: 1 in 1000 women over the age of 40 lives with PBC.
Seladelpar is a potent, selective, orally active PPARδ agonist that is in development for the treatment of the liver diseases PBC and NASH. For PBC, seladelpar has received an orphan designation from the US Food and Drug Administration (FDA) and the European Medicine Agency (EMA). Seladelpar also received Breakthrough Therapy Designation from the FDA and PRIority MEdicine status from the EMA for PBC.
ENHANCE (NCT03602560) is a 52-week, placebo-controlled, randomized, Phase 3 study to evaluate the safety and efficacy of seladelpar. It will be conducted in more than 20 countries over five continents (North America, South America, Europe, Australasia and Asia). Approximately 240 PBC patients will be randomized to seladelpar 10 mg/day, seladelpar 5/10 mg/day (starting treatment at 5 mg with the possibility to escalate dose to 10 mg after 6 months), or placebo. Patients must experience an inadequate response to UDCA (defined as a serum alkaline phosphatase level ≥ 1.67 x the upper limit of normal after at least 12 months of treatment) or an intolerance to UDCA to be eligible for the study. Patients who are inadequate responders to UDCA will continue their treatment during the study, and UDCA will be provided free of charge. The primary outcome measure is the responder rate after 52 weeks. A responder is defined as a patient who achieves an alkaline phosphatase level < 1.67 x the upper limit of normal with at least a 15% decrease from baseline and has a normal level of total bilirubin. Additional key outcomes of efficacy will compare the rate of normalization of alkaline phosphatase at 52 weeks and the level of pruritus at 6-months assessed by a numerical rating scale recorded with an electronic diary. Additional information can be found at https://www.clinicaltrials.gov/ct2/show/NCT03602560?term=seladelpar&rank=2. After completing the study, patients will be offered to continue treatment in an open label extension study. Patients on placebo will be offered to start seladelpar in the extension study.
CymaBay Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on developing therapies for liver and other chronic diseases with high unmet medical need. CymaBay’s lead development candidate, seladelpar, is a potent, selective and orally active PPARδ agonist currently in development for the treatment of patients with primary biliary cholangitis (PBC), an autoimmune liver disease, and with nonalcoholic steatohepatitis (NASH). CymaBay is currently enrolling patients in ENHANCE, a global, Phase 3 registration study of seladelpar for PBC. CymaBay is also conducting a Phase 2b proof-of-concept study of seladelpar in patients with NASH.
About Digestive Disease Week
Digestive Disease Week® (DDW) is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE) and the Society for Surgery of the Alimentary Tract (SSAT), DDW takes place May 18-21, 2019, at the San Diego Convention Center. The meeting showcases more than 5,000 abstracts and hundreds of lectures on the latest advances in GI research, medicine and technology. More information can be found at www.ddw.org.
The statements in this press release regarding the potential for seladelpar to treat PBC and NASH, the potential benefits to patients, CymaBay’s expectations and plans regarding future clinical trials and CymaBay’s ability to fund current and planned clinical trials are forward looking statements that are subject to risks and uncertainties. Actual results and the timing of events regarding the further development of seladelpar could differ materially from those anticipated in such forward-looking statements as a result of risks and uncertainties, which include, without limitation, risks related to: the success, cost and timing of any of CymaBay’s product development activities, including clinical trials; effects observed in trials to date that may not be repeated in the future; any delays or inability to obtain or maintain regulatory approval of CymaBay’s product candidates in the United States or worldwide; and the ability of CymaBay to obtain sufficient financing to complete development, regulatory approval and commercialization of its product candidates in the United States and worldwide. Additional risks relating to CymaBay are contained in CymaBay’s filings with the Securities and Exchange Commission, including without limitation its most recent Annual Report on Form 10-K and other documents subsequently filed with or furnished to the Securities and Exchange Commission. CymaBay disclaims any obligation to update these forward-looking statements except as required by law.