CymaBay's Seladelpar Achieves High Statistical Significance for the Primary and Key Secondary Endpoints in the Phase 3 RESPONSE Trial in Primary Biliary Cholangitis

Primary composite endpoint at 12 months of serum alkaline phosphatase and bilirubin was met by 61.7% of patients treated with seladelpar10 mgvs. 20.0% of placebo treated patients (p<0.0001)

Normalization of alkaline phosphatase at 12 months was achieved by 25.0% of patients treated with seladelpar vs. 0% on placebo (p<0.0001)

In patients having moderate-to-severe itch at baseline, the seladelpar treated group improved their pruritus at 6 months compared to those in the placebo group (p<0.005)

Safety and tolerability were comparable between placebo and seladelpar groups and consistent with previous studies

CymaBay will hold a conference call to discuss these results today at 8:00 a.m. ET

NEWARK, Calif., Sept. 7, 2023 /PRNewswire/ -- CymaBay Therapeutics, Inc. (NASDAQ: CBAY), a biopharmaceutical company focused on innovative therapies for patients with liver and other chronic diseases, today announced positive topline results from its Phase 3 pivotal RESPONSE study. The study evaluated the safety and efficacy of seladelpar, a potent, selective, orally active delpar or PPARδ agonist, in development for the treatment of adult patients with primary biliary cholangitis (PBC). The registration trial achieved the primary and all key secondary endpoints and supports advancement to regulatory discussions and filing for regulatory approval with the U.S. Food and Drug Administration (FDA), the Medicines and Healthcare products Regulatory Agency (MHRA), and the European Medicines Agency (EMA).

A total of 61.7% of patients on seladelpar 10 mg (n=128) met the primary composite endpoint related to serum alkaline phosphatase and bilirubin at 12 months versus 20.0% on placebo (n=65; p<0.0001). The anti-cholestatic effect of seladelpar was supported by the normalization of alkaline phosphatase at 12 months (key secondary endpoint) in 25.0% of patients on seladelpar vs. zero on placebo (p<0.0001). The least-squares mean percent reduction in alkaline phosphatase at 12 months was 42.4% in the seladelpar group vs. 4.3% in the placebo group (p<0.0001).

Seladelpar treatment compared to placebo also demonstrated a statistically significant reduction in pruritus, or itch, (key secondary endpoint) after 6 months of treatment. Seladelpar-treated patients with a baseline Numerical Rating Scale (NRS) ≥4 (moderate to severe pruritus) had a least-square mean reduction of 3.2 points in pruritus NRS (n=49) compared to 1.7 points for patients in the placebo group (n=23; p<0.005).

Overall, safety was comparable between placebo and seladelpar groups and was consistent with previous studies. Treatment-emergent adverse events, serious adverse events, and patient discontinuations were generally balanced across the treatment and placebo arms. There were no treatment-related serious adverse events in the study. Seladelpar's tolerability profile appeared favorable and consistent with previous studies. 

"The topline results seen in the RESPONSE trial are exciting for highlighting the potential for an efficacious and safe new therapy that not only achieves the composite improvements in liver tests, but for a significant proportion of patients, normalizes these measures. Further, the results support that seladelpar reduced itch, a particularly challenging symptom that continues to negatively impact quality of life for many PBC patients," said Gideon Hirschfield, M.D., Lily and Terry Horner Chair in Autoimmune Liver Disease Research, Toronto Centre for Liver Disease. "While existing first and second-line therapies have helped patients living with PBC, this is the first potential therapy to show promise in both significantly improving markers associated with risk of disease progression while also significantly reducing itch."

"The results from RESPONSE support our conviction that seladelpar has the potential to advance patient care by improving measures of disease activity and reducing symptom burden. They are consistent with previous findings in what we believe has been an exceptionally robust development program in PBC. We believe that the delpar mechanism is unique with its ability to normalize markers of cholestasis coupled with reductions in pruritus," said Sujal Shah, President and CEO of CymaBay. "Many patients with PBC suffer from incessant itching while knowing that their disease can progress to the point where a liver transplant could become their only option.  These results represent an important step toward potentially changing the treatment paradigm for patients living with PBC. We deeply appreciate the participation of patients across all of our studies in PBC and the support we have received from investigators, their teams and our many partners involved in advancing the development of seladelpar through this significant milestone."  

Additional analyses of RESPONSE are ongoing, and the company looks forward to sharing additional data in an upcoming medical meeting.

RESPONSE was a double-blind, placebo-controlled, global study of one-year duration that randomized 193 PBC patients in a 2:1 ratio to seladelpar 10 mg or placebo, once daily. Eligible patients had an inadequate response or intolerance to ursodeoxycholic acid (UDCA) with serum alkaline phosphatase (ALP) ≥ 1.67× the upper limit of normal (ULN) after at least 12 months of treatment. The primary outcome measure was the responder rate defined as a patient who achieved an ALP level < 1.67× ULN with ≥ 15% decrease in ALP, and total bilirubin (TB) ≤ 1.0× ULN after 52 weeks.

Secondary outcome measures were the proportion of patients with ALP ≤ 1.0× ULN at 12 months and the change from baseline at 6 months in the patient-reported level of pruritus as assessed by the NRS in those patients with baseline NRS ≥4. The NRS is a scale of 0 (no itching) to 10 (worst imaginable itching). At baseline, mean ALP levels were 314.3 U/L and TB 0.76 mg/dL and the mean baseline NRS was 6.3 in those patients evaluated for the pre-specified pruritus endpoint. The baseline characteristics were balanced between the two groups and representative of a high-risk PBC patient population with a high level of symptom burden.

Conference Call

CymaBay will host a conference call today, Thursday, September 7 at 8:00 a.m. ET to discuss the topline results from this study. To access the live conference call, please dial 877-407-0784 from the U.S. and Canada, or 201-689-8560 internationally, Conference ID# 13741034. To access the live and archived webcast of the conference call, go to the Investors section of the CymaBay website at http://ir.cymabay.com/events. A slide presentation to be referenced on the conference call will be available in the Investors section of the CymaBay website shortly before the call.

About PBC
PBC is a rare, chronic inflammatory liver disease primarily affecting women (1 in 1,000 women over the age of 40 or about 130,000 total people in the US). 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 ALP and total bilirubin. The most common early symptoms of PBC are pruritis (itching) and fatigue, which can be debilitating for some patients. Progression of PBC is associated with an increased risk of liver-related mortality.

About Seladelpar
Seladelpar, an investigational treatment for people with PBC, is a first-in-class oral, selective peroxisome proliferator-activated receptor (PPAR) delta 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 acid 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 investigational treatment for people with 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 X (formerly 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 future filing plans of CymaBay 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.

Public Relations Contact:                                              

Theresa Dolge
Evoke Kyne
(609) 915-2156
Theresa.Dolge@evokegroup.com

Investor Relations Contact:

Hans Vitzthum
LifeSci Advisors, LLC
(617) 430-7578
Hans@LifeSciAdvisors.com

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