CymaBay Therapeutics Announces the Initiation of its Next Phase 2 Study of Seladelpar (MBX-8025) in Patients with Primary Biliary Cholangitis

NEWARK, Calif., Dec. 07, 2016 (GLOBE NEWSWIRE) -- CymaBay Therapeutics, Inc. (NASDAQ:CBAY), a clinical-stage biopharmaceutical company developing therapies to treat indications with high unmet medical need, today announced the initiation of a new Phase 2 study of seladelpar in patients with primary biliary cholangitis (PBC).  

PBC is an orphan autoimmune disease affecting primarily women over the age of 40. The disease is characterized by the immune-mediated destruction of the small intrahepatic bile ducts resulting in the reduction of bile flow, a condition referred to as cholestasis. The accompanying build-up of toxic bile acids leads to chronic liver inflammation and fibrosis that may progress to cirrhosis and liver failure. Patients with PBC characteristically demonstrate an increase in serum alkaline phosphatase, a marker of cholestasis, and often experience pruritus and fatigue. Ursodiol and Ocaliva^® are the only FDA approved drugs for the treatment of PBC. However, many patients do not respond adequately to these therapies or have side effects. For these reasons, new treatments are needed.

"Following the promising results of our first proof-of-concept study demonstrating that seladelpar normalized alkaline phosphatase without being associated with pruritus, I am delighted that we have been able to initiate this new study so quickly.  We are grateful for the constructive feedback from the Food and Drug Administration as well as for the enthusiasm of investigators and patients," said Harold Van Wart, Ph.D., President and Chief Executive Officer of CymaBay.

In this open label study, patients who have had an inadequate response to, or are intolerant to, ursodiol will be enrolled to receive seladelpar, either 5 or 10 mg, for 8 weeks. Based on the review of the 8-week data, new patients will be enrolled to receive seladelpar 25 mg for 8 weeks. The study also incorporates an extension phase where patients will be able to continue treatment for a total of 26 weeks during which it will be possible to adjust the dose of seladelpar. The primary endpoint will be the change in alkaline phosphatase (ALP), a parameter that has been used in prior clinical studies with PBC and which is believed to reflect the status of the disease. A variety of secondary outcomes will also be studied. The study is designed to enroll approximately 36 patients in the U.S., Canada, Germany and the U.K.

An earlier Phase 2 study of seladelpar in subjects with PBC was terminated earlier this year when proof-of-concept was demonstrated by marked improvements in biochemical markers of cholestasis, including ALP. The study also identified a treatment emergent signal of transaminase elevations. The magnitude of the ALP reductions in the study suggested that lower doses may retain ALP reductions while avoiding transaminase elevations.

About Seladelpar

Seladelpar (MBX-8025) is a potent and selective agonist of PPARδ, a nuclear receptor important for lipid transport, storage and metabolism in liver and muscle. In a Phase 2 study in subjects with mixed dyslipidemia, seladelpar decreased LDL-C, triglycerides and high sensitivity CRP, a biomarker of inflammation. Seladelpar also decreased alkaline phosphatase and gamma glutamyl transferase, two key markers of cholestasis. In a recently completed Phase 2 study in subjects with primary biliary cholangitis (PBC), seladelpar decreased markers of cholestasis and inflammation without appearing to cause pruritus while also lowering LDL-C. In a diabetic obese model of nonalcoholic steatohepatitis (NASH), seladelpar reversed NASH and inhibited fibrosis suggesting it may have potential for the treatment of this condition.  The U.S. Food and Drug Administration (FDA) has granted CymaBay orphan drug designation for seladelpar as a treatment for PBC. In addition, seladelpar has been granted the PRIority MEdicines (PRIME) Designation for the treatment of PBC by the European Medicines Agency. CymaBay has also completed a pilot Phase 2 clinical study showing that seladelpar lowers LDL-C in patients with homozygous familial hypercholesterolemia (HoFH).  The FDA has also granted CymaBay orphan drug designation for seladelpar as a treatment for HoFH and Fredrickson types I and V hyperlipoproteinemias.

About PBC

Primary biliary cholangitis (PBC), formerly known as primary biliary cholestasis, 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, afflicting approximately one in 1,000 over the age of 40.

About CymaBay

CymaBay Therapeutics, Inc. (CBAY) is a clinical-stage biopharmaceutical company developing therapies to treat diseases with high unmet medical need, including serious rare and orphan disorders. Seladelpar is a potent, selective, orally active PPARδ agonist. CymaBay has recently completed a Phase 2 study of seladelpar in patients with primary biliary cholangitis as well as a pilot Phase 2 study in patients with homozygous familial hypercholesterolemia, establishing proof-of-concept in both indications.  Previously, a Phase 2 study of seladelpar in patients with mixed dyslipidemia established that it has an anti-atherogenic lipid profile.  Arhalofenate, CymaBay’s other product candidate, is a potential Urate-Lowering Anti-Flare Therapy that has completed five Phase 2 studies in gout patients. Arhalofenate has been found to reduce painful flares in joints while at the same time promoting excretion of uric acid by the kidney. This dual action addresses both the signs and symptoms of gout while managing the underlying pathophysiology of hyperuricemia.

Cautionary Statements

The statements in this press release regarding the potential use of seladelpar for the treatment of PBC and the potential future performance of CymaBay's product candidates are forward looking statements that are subject to risks and uncertainties. Actual results and the timing of events regarding the further development of CymaBay’s product candidates 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 of seladelpar and arhalofenate; effects observed in trials to date which 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 Quarterly Report on Form 10-Q 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.

For additional information about CymaBay visit www.cymabay.com.

Contacts:

Sujal Shah
CymaBay Therapeutics, Inc.
(510) 293-8800
sshah@cymabay.com

or

Hans Vitzthum
LifeSci Advisors, LLC
(212) 915-2568
Hans@LifeSciAdvisors.com

Released December 7, 2016