The company will be trialling the drug for patients with compensated cirrhosis due to primary biliary cholangitis (PBC). CymaBay is focused on providing therapies for patients with liver and other chronic diseases.
Approximately 192 patients with PBC who have compensated cirrhosis, based on prespecified clinical criteria, have been selected for the study. Candidates must be Child-Pugh A or B on the scale, which is used to describe the clinical state of patients with liver cirrhosis and to assess the severity of the condition.
They will be randomly assigned using a 2:1 ratio to oral once daily seladelpar or placebo for a fixed duration of three years.
The primary outcome measure is the time from start of treatment to the first occurrence of clinical events (all-cause death, liver transplant, hospitalization for other serious liver-related events, and progression to Child-Pugh C decompensated cirrhosis). Additional key outcomes include overall survival, liver transplant free survival, and time to hospitalization for serious liver-related events.
Charles McWherter, chief scientific officer and president of research and development at CymaBay said: “The Affirm study was initiated to characterize the efficacy and safety of seladelpar in a PBC population with advanced disease. It is designed to fulfill post-marketing requirements of the accelerated approval pathway for seladelpar to confirm its benefit on clinical outcomes.
“Over the past few years, we have had significant interactions with regulators to develop a study in the backdrop of many known operational and ethical challenges in conducting a placebo-controlled long-term outcomes study.
“We selected this population and design to establish the effect of seladelpar on clinical outcomes. We remain fully committed to meeting our scientific and regulatory commitments while prioritizing the health of people living with 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). It 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.
“The goal of therapy in patients with PBC is to prevent progression to end-stage liver disease and liver failure, however, carrying out placebo-controlled outcomes trials is challenging due to the long natural history of PBC.
“I am pleased to learn that the study will aim to confirm the benefit of seladelpar in patients with PBC over a three-year period, which is the shortest timeframe we have seen to date for a confirmatory trial,” said Kris Kowdley, director of Liver Institute Northwest, and professor at the Elson S. Floyd College of Medicine, Washington State University.