CymaBay Therapeutics, Inc., has initiated a Phase 3b/4 study called AFFIRM to evaluate the effect of seladelpar on clinical outcomes in patients with cirrhosis due to PBC.

 

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Primary Biliary Cholangitis (PBC) is a rare, chronic inflammatory liver disease that primarily affects women. It is characterized by impaired bile flow and the accumulation of toxic bile acids in the liver. This leads to inflammation and destruction of the bile ducts. This condition can cause significant symptoms such as itching and fatigue. It also carries an increased risk of liver-related mortality. 

 

AFFIRM Study

The AFFIRM study is a randomized, placebo-controlled confirmatory trial designed to assess the efficacy and safety of seladelpar in patients with compensated cirrhosis due to PBC. Approximately 192 patients with Child-Pugh A or Child-Pugh B cirrhosis will be enrolled in the study. The patients will be randomly assigned to receive either oral, once-daily seladelpar or placebo for a fixed duration of three years. 

The primary outcome measure of the study is the time from the start of treatment to the occurrence of clinical events. Events include all-cause death, liver transplant, hospitalization for other serious liver-related events, and progression to decompensated cirrhosis. Secondary outcomes include overall survival, liver transplant-free survival, and time to hospitalization for serious liver-related events. 

The goal of therapy in patients with PBC is to prevent progression to end-stage liver disease and liver failure. However, conducting placebo-controlled outcomes trials in PBC is challenging due to the long natural history of the disease. The AFFIRM study aims to overcome these challenges by providing evidence of the efficacy and safety of seladelpar in a three-year timeframe, which is the shortest duration seen to date for a confirmatory trial in PBC. 

Dr. Kris V. Kowdley, Director of Liver Institute Northwest and Professor at the Elson S. Floyd College of Medicine, Washington State University, expressed his satisfaction with the study design. He highlighted the importance of confirming the benefit of seladelpar in patients with PBC and emphasized the need for shorter duration trials in this population. 

 

The Role of Seladelpar 

Seladelpar is an investigational treatment for people with PBC. It belongs to a class of drugs called selective peroxisome proliferator-activated receptor (PPAR) delta agonists. Preclinical and clinical data suggest that seladelpar can regulate genes involved in bile acid synthesis, inflammation, fibrosis, and lipid metabolism, storage, and transport. 

The potential of seladelpar to treat PBC and improve clinical symptoms or outcomes of the disease is the focus of the AFFIRM study. The study aims to provide robust evidence supporting the use of seladelpar as a therapeutic option for patients with cirrhosis due to PBC. 

The initiation of the AFFIRM study marks an important milestone in the evaluation of seladelpar’s effect on clinical outcomes in patients with cirrhosis due to PBC. By conducting a randomized, placebo-controlled confirmatory trial, CymaBay Therapeutics aims to provide robust evidence supporting the use of seladelpar as a therapeutic option for PBC. The study’s unique design and shorter duration aim to overcome the challenges associated with conducting placebo-controlled outcomes trials in PBC. Through its scientific and regulatory commitments, CymaBay Therapeutics remains dedicated to improving the lives of people with liver and other chronic diseases. 

 

 

To learn more about Primary Biliary Cholangitis and other liver diseases, visit checkrare.com/diseases/gastrointestinal-diseases/ 

 

 

Reference 

https://www.globenewswire.com/news-release/2023/09/21/2747218/37067/en/CymaBay-Initiates-AFFIRM-a-Phase-3b 4-Study-Evaluating-the-Effect-of-Seladelpar-on-Clinical-Outcomes-in-Patients-with-Cirrhosis-due-to-Primary-Biliary-Ch olangitis.html