CymaBay Therapeutics, Inc. (NASDAQ: CBAY), a clinical-stage biopharmaceutical company focused on developing therapies for liver and other chronic diseases with high unmet need, today announced positive data from its previously completed Phase 2 study and the ENHANCE Phase 3 study of seladelpar in patients with primary biliary cholangitis (PBC).
These data are being presented at The International Liver Congress 2021 of the European Association for the Study of Liver (EASL) which will be held online June 23rd - 26th.
In a poster presentation titled 'Efficacy, safety, and tolerability of seladelpar in patients with compensated liver cirrhosis due to primary biliary cholangitis (PBC): a pooled analysis of phase 2 and phase 3 studies,'1 Stuart C. Gordon MD, Director of Hepatology for Henry Ford Health Systems, will be reporting the results of a pooled analysis of a subset of 39 patients with compensated cirrhosis from an open-label phase 2 study and a placebo (Pbo) controlled phase 3 study (ENHANCE) assessing the efficacy, safety, and tolerability of seladelpar at a daily dose of 5 mg or 10 mg in PBC patients who had an inadequate response or an intolerance to ursodiol. Cirrhosis was diagnosed using liver biopsy, imaging tests, or liver elastography.
Efficacy analyses at 3 months included:
Composite response defined as alkaline phosphatase (ALP) < 1.67 x upper-limit-normal, ALP decrease of 15% and normal total bilirubin
Percent change from baseline in ALP
Normalization of ALP levels
Other measures of liver function
After 3 months, the composite endpoint was met in 50% of patients in the 5 mg and 63% in the 10 mg groups compared to none in Pbo. Levels of total bilirubin, platelets, albumin, and coagulation parameters remained stable. Seladelpar was well tolerated and appeared safe. Three patients with cirrhosis experienced an SAE, all unrelated to seladelpar. Efficacy, tolerability, and safety in patients with compensated cirrhosis were comparable to that of non-cirrhotic patients.
'These findings suggest that seladelpar may provide an effective treatment option for patients with compensated cirrhosis due to PBC,' said Dr. Gordon. 'In addition, seladelpar treatment appeared to be safe and was well tolerated which is encouraging given the high unmet need that exists in this population. Confirmation of these findings in the ongoing RESPONSE Phase 3 pivotal study would be an important advancement in the treatment of PBC.'
A second clinical presentation2 will be delivered by Dr. Aliya Gulamhusein, Assistant Professor and Clinical Investigator at the Toronto Centre for Liver Disease, demonstrating that in 51 PBC patients previously treated with but no longer taking obeticholic acid (OCA) or fibrates, seladelpar appeared to be safe, well tolerated and showed meaningful and dose dependent improvements in liver biochemistry, including in those taking 10 mg seladelpar a 45% reduction in ALP and a 79% composite response rate. In addition, there were no meaningful differences in the effects of seladelpar treatment between those with prior treatment with OCA or fibrates compared to those without prior treatment.
Additionally, a presentation3 by Dr. Paul Watkins, Professor of Medicine at the University of North Carolina Chapel Hill, will highlight the ajudication of suspected drug-induced liver injury (DILI) in non-alcoholic steatohepatitis (NASH) patients using independent blinded review by a panel of pathologists and hepatologists. A comprehensive process of adjudication found no clinical, biochemical or histologic evidence that seladelpar was hepatotoxic. The process included two extensive rounds of blinded randomized review of all biopsies in the study. The panel concluded that there were no specific cases that were suggestive of DILI and the features identified by the study pathologists were present at baseline. The outcome of the pathology review indicates a need for further research into disease-related changes in the portal tracts of the livers of NASH patients. The panel also recommended that future biopsy trials in NASH should use blinded concurrent review of baseline and end of treatment biopsies. The report from the panel was subsequently submitted to the FDA and the FDA lifted the clinical hold on seladelpar across all three indications.
Finally, a preclinical presentation4 will highlight that the combination of seladelpar and CB-0406 in a mouse model of NASH led to substantially greater reductions in fibrosis and NASH than either monotherapy.
Dr. Dennis Kim, Chief Medical Officer of CymaBay Therapeutics, commented, 'The positive clinical results highlight the potential for seladelpar to offer PBC patients with different stages of disease and different prior treatment experience an efficacious and safe treatment option. 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.'
Presentations at The International Liver Congress 2021 include:
1'Efficacy, safety, and tolerability of seladelpar in patients with compensated liver cirrhosis due to primary biliary cholangitis (PBC): a pooled analysis of phase 2 and phase 3 studies' (Abstract #1809)
Stuart C Gordon, Palak Trivedi, Christopher Bowlus, Michael Galambos, Aparna Goel, Aliya Gulamhusein, Cynthia Levy, Guy Neff, Carmen Stanca, Douglas Thorburn, Bruce Bacon, Brian Borg, Yvonne Doerffel, Lisa Forman, Bradley Freilich, Liana Gheorghe, Maria Sarai Gonzalez, Stephen Harrison, Jonathan Huang, Sook-Hyang Jeong, Seung Up Kim, John Lake, Joseph Odin, Won Young Tak, Hillel Tobias, John M. Vierling, Ke Yang, Alexandra (Sasha) Steinberg, Yun-Jung Choi, Charles McWherter, Marlyn J. Mayo
2'Treatment with seladelpar in patients with primary biliary cholangitis (PBC) and prior experience with obeticholic acid (OCA) or fibrates' (Abstract #2120)
Aliya Gulamhusein, Guy Neff, Aparna Goel, Marlyn J. Mayo, Carmen Stanca, Christopher Bowlus, Lisa Forman, Pietro Invernizzi, Frederik Nevens, Ehud Zigmond, Eli Zuckerman, Ke Yang, Yun-Jung Choi, Alexandra (Sasha) Steinberg, Charles McWherter, Kris V. Kowdley
3'An independent blinded review of suspected drug-induced liver injury (DILI) in nonalcoholic steatohepatitis (NASH) patients by a panel of pathologists and hepatologists: lessons learned from the seladelpar hepatoxicity review committee (SHRC)' (Abstract # 1504)
Paul Watkins, David E Kleiner, Pierre Bedossa, Zack Goodman, Neil Kaplowitz, Willis Maddrey, John M. Vierling, Michael Charlton, Cynthia Guy, Elizabeth Brunt, Stephen Harrison, Edward Cable, Yun-Jung Choi, Sujal Shah, Klara Dickinson, Charles McWherter
4'Effect of seladelpar and CB-0406 combination therapy on obesity, liver fibrosis and steatosis in a diet-induced obese (DIO) mouse model of biopsy-confirmed non-alcoholic steatohepatitis (NASH) with fibrosis' (Abstract #1797)
Yun-Jung Choi, Jeffrey Stebbins, Ed Cable, Jiangao Song, Jeff Johnson, Charles McWherter
Congress attendees can visit CymaBay throughout the virtual meeting at the CymaBay microsite. A full list of presentations can be found on The International Liver Congress 2021 website. The presentations will also be made available later this month on the CymaBay website.
About Seladelpar
Seladelpar is a potent, selective, orally active PPAR agonist that has been in development for the treatment of the liver diseases primary biliary cholangitis (PBC) and nonalcoholic steatohepatitis (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 for early stage PBC and PRIority MEdicine status from the EMA.
About CymaBay
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 (U.S. Food and Drug Administration), PRIority MEdicines status (European Medicines Agency) and orphan drug status (U.S. 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.
Cautionary Statements
The statements in this press release regarding the potential for seladelpar to treat NASH or PBC, the potential benefits to patients, CymaBay's expectations and plans regarding its current and 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 or to potentially restart clinical trials. 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.
Contact:
Glenn Silver
Tel: (973) 818-8198
Email: Glenn.silver@finnpartners.com
CYMABAY THERAPEUTICS, INC. 
