CYMABAY THERAPEUTICS, INC. Bowlus CL, Galambos MR, Aspinall RJ, Hirschfield GM, Jones DEJ, Dörffel Y, Gordon SC,
This 52-week, phase 2, dose-ranging, open-label study examined the efficacy and safety of seladelpar, a selective peroxisome proliferator-activated receptor-delta agonist, in adults with PBC who were receiving or intolerant to first-line therapy with ursodeoxycholic acid. Eligible patients were enrolled with a minimum serum alkaline phosphatase (ALP) levels of 1.67 times the upper-limit-of-normal (194 U/L) and which were on average in excess of 318 U/L. Seladelpar was administered orally once daily at 2 mg (n=11), 5 mg (n=53) or 10 mg (n=55) for 12 weeks, after which doses could be increased up to 10 mg if needed to improve treatment response. Cirrhosis was present in 21% of patients; 71% had pruritus.
An interim primary efficacy analysis of ALP change from baseline at Week 8 found that seladelpar treatment provided 26%, 33%, and 41% reductions for the 2 mg, 5 mg and 10 mg doses, respectively (all p<0.005). Responses were maintained or improved at Week 52 which included dose escalation in 91% and 80% of the 2 mg and 5 mg cohorts, respectively. At Week 52, the composite biochemical response (ALP <1.67×ULN, ≥15% ALP decrease from baseline, and normal total bilirubin) rates were 64%, 53%, and 67%, and ALP normalization rates were 9%, 13%, and 33% in the 2 mg, 5 mg, and 10 mg cohorts, respectively. The pruritus visual analog scale score was also decreased in the 5 mg and 10 mg cohorts. There were no treatment-related serious adverse events (AEs), and 4 patients discontinued due to AEs.
Lead investigator Professor
A companion manuscript of results from this study were also published in the journal
Kremer AE, Mayo MJ, Hirschfield G,
Professor
CymaBay is currently enrolling RESPONSE, a global phase 3 study of seladelpar in patients with PBC that is intended to confirm these results. Seladelpar’s development program also includes ASSURE, a global phase 3 long-term study that is expected to contribute safety and efficacy data on more than 300 patients treated with seladelpar.
About PBC
PBC is a rare, chronic autoimmune 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 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
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, CymaBay’s expectations and plans regarding its current and future clinical trials, including the timing of enrollment in RESPONSE, the impact of the COVID pandemic on the enrollment timeline for CymaBay’s 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
For additional information about CymaBay, visit www.cymabay.com.
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