▎WuXiEdited by Kant Content Team

Gilead Sciences today announced positive interim results from the ongoing ASSURE study. Analysis shows that adult patients with primary biliary cholangitis (PBC) who received the investigational drug seladelpar experienced reductions in cholestatic biomarkers and inflammation, as well as improvements in pruritus.The U.S. FDA has accepted seladelparFor the treatment of PBC patients's new drug application and granted it priority review status, which includes the treatment of pruritus symptoms as well as adult patients with non-cirrhotic or compensated cirrhotic conditions who respond inadequately or are intolerant to ursodeoxycholic acid (UDCA).The FDA is expected to announce the review results by August 14, 2024. In addition, the UK Medicines and Healthcare products Regulatory Agency (MHRA) and the European Medicines Agency (EMA) have also accepted the marketing review of seladelpar.

Primary Biliary Cholangitis is a potentially life-threatening autoimmune liver disease. Due to the immune system continuously attacking the bile ducts, bile flow is obstructed and accumulates, causing toxic bile acids to remain in the liver, which can progress to liver fibrosis, cirrhosis, and liver failure. Other clinical symptoms include fatigue and itching. One in a thousand women over the age of 40 are affected by PBC.

ASSURE is an open-label study designed to evaluate the long-term safety and efficacy of seladelpar. ASSURE enrolled adult PBC patients who had previously participated in seladelpar studies, with key eligibility criteria including inadequate response to or intolerance of UDCA. The majority of patients in the ASSURE trial were female (94%), with an average age of 59 years. Baseline characteristics included a mean alkaline phosphatase (ALP) level of 270.5 U/L and total bilirubin (TB) value of 0.75 mg/dL; 19% of enrolled patients met the criteria for cirrhosis. The study assessed several predefined biochemical endpoints. The composite response endpoint included ALP below the upper limit of normal (ULN).1.67 timesALP decreased by at least 15% and total TB value is below ULN.

As of June 29, 2023,Of the 148 patients who completed 12 months of treatment, 70% achieved a clinically meaningful composite response endpoint. In patients treated with seladelpar, 37% had normalization of ALP, with an average ALP change of -44% (-144.4 U/L).Of the 20 patients who completed 24 months of treatment, 70% achieved a composite response endpoint and 25% of patients had normalized ALP. Seladelpar also reduced other important biomarkers of liver injury, including TB, γ-glutamyl transferase (GGT), and alanine aminotransferase (ALT) levels, with reductions of 9%, 36%, and 25% from baseline, respectively.

In terms of safety, no serious adverse events related to the treatment were reported in the study. Seladelpar was generally well-tolerated, with 4.6% of patients discontinuing the medication due to adverse events.

▲Seladelpar Molecular Formula (Image Source: PubChem)

Seladelpar is an investigational, oral, potential "first-in-class" potent selective peroxisome proliferator-activated receptorδ(PPARδ) agonist.PPARδ is expressed in various cell types in the liver. Preclinical data indicate that it regulates multiple genes involved in bile acid synthesis, inflammation, and fibrosis processes. The drug received Breakthrough Therapy Designation from the U.S. FDA in February 2019 for the treatment of PBC. Originally developed by CymaBay, Gilead Sciences reached an agreement with the company in February 2024 for a total amount of $4.3 billion.Acquisition Agreement, and thereby secure this therapeutic option.