Total of 181 subjects enrolled with elevated liver fat and biopsy-confirmed NASH
Over 80% of subjects had baseline F2 or F3 stage fibrosis
Subjects were randomized to seladelpar 10 mg, 20 mg or 50 mg or placebo
- Twelve-week topline liver fat data, using MRI-PDFF, expected 2Q 2019
NEWARK, Calif., Feb. 19, 2019 (GLOBE NEWSWIRE) -- CymaBay Therapeutics, Inc. (NASDAQ: CBAY), today announced the early completion of enrollment in a Phase 2b dose-ranging, paired liver biopsy study of seladelpar for the treatment of nonalcoholic steatohepatitis (NASH). The company expects to report 12-week topline results on changes in liver fat and key biochemical parameters in the second quarter.
The randomized, placebo-controlled study enrolled 181 subjects who had a diagnosis of NASH with fibrosis established by liver biopsy. Prior to a baseline biopsy, subjects were required to have a liver fat content greater than 10% using the magnetic resonance imaging proton density fat fraction (MRI-PDFF) method. Subjects were randomized to receive either seladelpar 10 mg, 20 mg, or 50 mg or placebo once daily. In addition, subjects were stratified at randomization by the stage of liver fibrosis and the presence or absence of type 2 diabetes. The evaluation of baseline liver histology confirmed that subjects had well-established NASH with a mean NAFLD Activity Score (NAS) of 5.2, which was accompanied by fibrosis with 150 subjects having stage 2 or 3 fibrosis. Other key baseline characteristics included a mean liver fat fraction by MRI-PDFF of 21% as well as elevated mean ALT and AST levels of 62 U/L and 46 U/L, respectively. Approximately half of the subjects enrolled had a diagnosis of type 2 diabetes at baseline.
The primary efficacy outcome is the relative reduction in liver fat by MRI-PDFF at 12 weeks. Important secondary measures are the evaluation of the histological improvement at 52 weeks in NASH pathology and fibrosis using paired liver biopsy samples. Additional planned assessments include MRI-PDFF evaluations at 26 and 52 weeks, magnetic resonance elastography (MRE) and other non-invasive imaging technologies, multiple biochemical markers, and an innovative digital liver pathology evaluation using machine learning algorithms.
"In spite of the widespread prevalence of NASH, the challenges of identifying and recruiting patients has often resulted in extended timelines in clinical development. The interest in seladelpar as a potential treatment for NASH, the screening algorithms implemented in this study and the hard work of our collective teams allowed for completion of enrollment ahead of schedule. Importantly, our screening approach led to a higher proportion of subjects with F2 and F3 fibrosis than has been seen in similar recent phase 2 studies. The enrolled patients are reflective of the noncirrhotic population targeted for phase 3 registration studies," said Stephen Harrison, MD, Medical Director of Pinnacle Clinical Research, founder of Summit Clinical Research and the principal coordinating investigator of the seladelpar Phase 2b NASH study.
Dr. Pol Boudes, Chief Medical Officer of CymaBay Therapeutics commented, “Partnering with Stephen and leveraging Summit’s NASH clinical trial site network helped us recruit the study ahead of schedule while targeting an appropriate study population for future NASH therapies. Based on its mechanism of action, seladelpar has the potential to correct pathways implicated in the pathogenesis of NASH and fibrosis. Our study uses the best and most recent technologies available to provide a comprehensive profile of seladelpar’s metabolic, anti-inflammatory and anti-fibrotic effects. We believe our study also meets the key requirements highlighted in recent FDA and EMA guidance for the evaluation of compounds in late phase 2 development for NASH. Once again, we thank all the patients participating in our clinical studies, their physicians and the clinical research team members that tirelessly support them.”
Nonalcoholic steatohepatitis involves the development of a fatty liver that, in patients at risk, triggers inflammation and hepatocellular injury with or without liver fibrosis. The prevalence of nonalcoholic fatty liver disease is increasing, with estimates ranging from 20% to 40% of adults in countries adopting a western diet. Ten to 20% of patients with fatty liver disease progress to nonalcoholic steatohepatitis. Patients with nonalcoholic steatohepatitis are at increased risk of cirrhosis and hepatocellular carcinoma, and nonalcoholic steatohepatitis is projected in the coming years to be the leading reason for liver transplant. Further, most patients with nonalcoholic steatohepatitis have coexisting obesity, insulin resistance with or without type 2 diabetes, hypertension, and dyslipidemia manifested by high serum cholesterol and triglycerides levels.
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 and the European Medicine Agency. Seladelpar also received Breakthrough Therapy Designation from the FDA and PRIority MEdicine status from the EMA for PBC.
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). Two Phase 2 studies of seladelpar established proof-of-concept in PBC. CymaBay is currently enrolling patients in a global, Phase 3 registration study of seladelpar for PBC. This study is a 52-week, placEbo-coNtrolled, randomized, pHAse 3 study to evaluate the safety aNd effiCacy of sEladelpar (ENHANCE) in patients with PBC. CymaBay is also conducting a Phase 2b proof-of-concept study of seladelpar for patients with NASH.
The statements in this press release regarding the potential for seladelpar to treat PBC and NASH, the potential benefits to patients, the timing of future data releases, the expected registration requirements for NASH treatments, 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.