RARE Daily

CymaBay Reports Positive Results in Late-Stage Study of Seladelpar in Rare Liver Disease

September 7, 2023

Rare Daily Staff

CymaBay Therapeutics reported positive topline results from its phase 3 pivotal RESPONSE study of its experimental therapy seladelpar to treat the rare liver disease primary biliary cholangitis that showed it met all primary and secondar endpoints.

Primary biliary cholangitis (PBC) is a chronic, inflammatory liver disease primarily affecting women over the age of 40 or about 130,000 total people in the United States. PBC is characterized by impaired bile flow 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 itching and fatigue, which can be debilitating for some patients. Progression of PBC is associated with an increased risk of liver-related mortality.

Seladelpar, an experimental treatment for people with PBC. It 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.

A total of 61.7 percent of patients on seladelpar met the primary composite endpoint related to serum alkaline phosphatase and bilirubin at 12 months versus 20.0 percent on placebo. The anti-cholestatic effect of seladelpar was supported by the normalization of alkaline phosphatase at 12 months (key secondary endpoint) in 25.0 percent of patients on seladelpar vs. zero on placebo.

Seladelpar treatment compared to placebo also demonstrated a statistically significant reduction in itching (key secondary endpoint) after six months of treatment.

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 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. 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.”

Photo: Sujal Shah, president and CEO of CymaBay

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