CymaBay Therapeutics Announces Publication of Results From the ENHANCE, Phase 3 Study of Seladelpar in Patients with Primary Biliary Cholangitis (PBC)

NEWARK, Calif., April 21, 2023 (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 that results from the ENHANCE phase 3 global study evaluating seladelpar for primary biliary cholangitis (PBC) have been published in Hepatology:

Seladelpar efficacy and safety at 3 months in patients with primary biliary cholangitis: ENHANCE, a phase 3, randomized, placebo-controlled study

by Hirschfield, GM; Shiffman, ML; Gulamhusein, A; Kowdley, KV; Vierling, JM; Levy, C; et al^.1 in Hepatology (2023), doi: 10.1097/HEP.0000000000000395

This double-blind, placebo-controlled, global phase 3 study evaluated the efficacy and safety of seladelpar, a potent, selective, orally active PPARδ agonist, or delpar, after 3 months of treatment in patients with PBC. Patients with elevated alkaline phosphtase (≥ 1.67x upper-limit-of-normal) received treatment as an add-on to first line ursodeoxycholic acid (UDCA), or as monotherapy, if patients were intolerant to UDCA. All pre-specified endpoints were assessed after 3 months in patients receiving oral daily seladelpar 5 mg (n=56), 10 mg (n=55) or placebo (n=56). The primary endpoint was a composite of alkaline phosphatase and bilirubin² previously accepted by FDA for pivotal studies in PBC. The composite endpoint was achieved in 78.2% of patients on seladelpar 10 mg and 57.1% on seladelpar 5 mg versus 12.5% on placebo (both seladelpar doses with p<0.0001). A key secondary endpoint of having normal levels of alkaline phosphatase was met in 27.3% (p<0.0001) and 5.4% (p=0.08) in seladelpar 10 mg and 5 mg groups, respectively, versus none in the placebo group. The final key secondary endpoint assessed the patient-reported symptom of pruritus (itching) using a daily pruritus numerical rating scale (NRS; 0-10). Statistically significant improvement in pruritus (p<0.02) for patients with moderate-to severe itch (NRS ≥4) was demonstrated for seladelpar 10 mg versus placebo. Patients taking seladelpar also had significant improvements in markers of liver injury. There were no treatment related adverse endpoints in the study.

Lead author and investigator Professor Gideon Hirschfield, FRCP PhD, Lily and Terry Horner Chair in Autoimmune Liver Disease at the University of Toronto, commented, “Patients with PBC are in need of new therapies that are well tolerated and provide clinical benefits. Data from this study support continued development of seladelpar for patients with PBC. Seladelpar has the potential to offer anti-cholestatic, anti-inflammatory and anti-pruritic benefits for patients at a higher risk of disease progression and for those continuing to suffer from symptom burden.”

Seladelpar is currently being evaluated in RESPONSE, a global phase 3 registration study in patients with PBC, that is expected to read out in the third quarter of 2023. Seladelpar’s development program also includes ASSURE, a global phase 3 long-term study that allows continued treatment with seladelpar in study subjects completing a prior seladelpar study. It is expected that ASSURE will contribute safety and efficacy data on more than 300 patients treated with seladelpar.

¹ The full list of authors is Hirschfield, GM; Shiffman, ML; Gulamhusein, A; Kowdley, KV; Vierling, JM; Levy, C; Kremer, AE; Zigmond, E; Andreone, P; Gordon, SC; Bowlus, CL; Lawitz, EJ; Aspinall, Richard J.; Pratt, DS; Raikhelson, K; Gonzalez-Huezo, MS; Heneghan, MA; Jeong, SH; Ladrón de Guevara, AL; Mayo, MJ; Dalekos, GN.; Drenth, JPH; Janczewska, E; Leggett, B.; Nevens, F; Vargas, V; Zuckerman, E; Corpechot, C; Fassio, E; Hinrichsen, H; Invernizzi, P; Trivedi, PJ; Forman, L; Jones, DEJ; Ryder, SD; Swain, MG; Steinberg, A; Boudes, PF; Choi, YJ; McWherter, CA.

² The composite biochemical endpoint response is defined as an alkaline phosphatse [ALP] < 1.67× ULN with a ≥ 15% ALP decrease from baseline and normal total bilirubin.

About PBC
PBC is a rare, chronic inflammatory 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.

About Seladelpar
Seladelpar is a first-in-class oral, selective PPARδ agonist, or delpar, 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.

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. To learn more, visit www.cymabay.com and follow us on Twitter and Linkedin.

Cautionary Statements
Any statements made in this press release regarding the potential for seladelpar to treat PBC and potentially improve clinical symptoms of the disease, the potential benefits to patients and the anticipated timing of the release of clinical data 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; and effects observed in trials to date that may not be repeated in the future. 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, its Quarterly Reports 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.

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