CymaBay Therapeutics, Inc. announced that the U.S. Food and Drug Administration (FDA) accepted its New Drug Application (NDA) for seladelpar, an investigational treatment for the management of primary biliary cholangitis (PBC) including pruritus in adults without cirrhosis or with compensated cirrhosis (Child Pugh A) who are inadequate responders or intolerant to ursodeoxycholic acid. The FDA has granted priority review and set a Prescription Drug User Fee Act (PDUFA) target action date of August 14, 2024 and notified the company that it is not currently planning to hold an advisory committee meeting to discuss the application. PBC is a rare, chronic condition that can lead to inflammation and eventually liver cirrhosis.

Disease progression is associated with an increase in liver-related complications, including mortality. People living with PBC can also experience symptoms that significantly impact their quality of life such as pruritus (itch) and fatigue. New treatment options seek to help prevent further disease progression by reducing inflammation and bile acids in the liver and help provide meaningful relief of pruritus.

Seladelpar is an investigational, potent, selective, orally active PPARd agonist, or delpar, in development for PBC treatment. It is the only investigational agent to have demonstrated a statistically significant improvement in biochemical markers of disease progression and pre-specified measures of PBC-related pruritus in a Phase 3 study. The safety profile of seladelpar in the pivotal Phase 3 RESPONSE study, measured through rates of adverse events, was similar in those treated with seladelpar and placebo.

The NDA includes data from across the seladelpar PBC clinical development program in over 500 participants living with PBC, including from the placebo-controlled Phase 3 RESPONSE and ENHANCE studies, the long-term open-label ASSURE study, and prior Phase 2 studies. The FDA has previously granted seladelpar Breakthrough Therapy Designation (BTD) which enabled early submission of select non-clinical data through the rolling review process afforded by seladelpar's BTD status. FDA updated the Breakthrough Therapy Designation for seladelpar in October 2023 in recognition of clinical data that indicated seladelpar may provide meaningful improvement over existing therapy based on a reduction in alkaline phosphatase (ALP) and improvement in pruritus in patients without cirrhosis or with compensated cirrhosis.

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, ALT, and GGT, enzymes found primarily in the liver, as well as total bilirubin. The most common early symptoms of PBC are pruritus (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 investigational treatment for people with PBC, is a first-in-class oral, selective peroxisome proliferator-activated receptor delta (PPARd) agonist, or delpar, shown to regulate critical metabolic and 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.