Seladelpar: A New Treatment for Primary Biliary Cholangitis

Seladelpar, a medication developed by Gilead, has received conditional approval for the treatment of primary biliary cholangitis (PBC), an autoimmune disease affecting the liver. This condition leads to the destruction of cholangiocytes, the cells lining the intrahepatic bile ducts, resulting in progressive liver inflammation and potential organ failure.

Indicated for adults who do not respond adequately to Ursodeoxycholic acid (UDCA) or cannot tolerate it, Seladelpar is administered in a dosage of 10 mg once daily, with or without food. Should a patient miss a dose, they are advised to take it at the next scheduled time but must avoid doubling the dose. No adjustment is necessary for mild liver dysfunction; however, in cases of moderate liver impairment, treatment discontinuation may be considered. The use of Seladelpar is not recommended for patients with severe liver dysfunction.

PBC is characterized as a rare, chronic autoimmune liver condition that inflicts gradual damage to the intrahepatic bile ducts. It predominantly affects women, with autoimmune processes leading to the destruction of cholangiocytes and subsequent bile accumulation (cholestasis). This can cause elevated levels of alkaline phosphatase and bilirubin. If left untreated, PBC can result in severe liver damage, inflammation, and fibrosis, ultimately leading to complications such as cirrhosis, liver cancer, chronic organ failure, and even death. In severe cases, patients may require liver transplantation.

Patients suffering from PBC often experience extrahepatic symptoms, with itching and fatigue being particularly burdensome. Notably, the level of fatigue does not always correlate with the severity of the liver disease.

The first-line treatment for PBC is UDCA, typically administered at a dosage of 13 to 15 mg per kg of body weight per day. Approximately 40% of patients do not respond sufficiently to this therapy, and about 5% report experiencing intolerance. For these patients, second-line treatments such as Elafibranor and now Seladelpar, in conjunction with UDCA, have been introduced. Both new agents can also be used as monotherapy.