Gilead Sciences Submits IND Application in China for Breakthrough Therapy Seladelpar in Primary Biliary Cholangitis

▎WuXi AppTec Content Team Report

Studies have shown that PPARδ can regulate key metabolic and liver disease-related pathways. Preclinical and clinical data indicate,Seladelpar has anti-cholestatic, anti-inflammatory, anti-pruritic, and anti-fibrotic effects.This therapy was originally developed by CymaBay, and in February 2024, Gilead Sciences reached a $4.3 billion acquisition agreement with the company, thereby obtaining this therapy.

Seladelpar has been approved by the U.S. FDA in August 2024.Accelerated Approval(Product name Livdelzi), used for the treatment of PBC. The product alsoIt has previously received Breakthrough Therapy Designation from the FDA, Orphan Drug Designation for PBC patients, and PRIME eligibility from the European Medicines Agency.

RESPONSE StudyIt is an international multicenter Phase 3 trial,Include PBC patients with poor response or intolerance to ursodeoxycholic acid (UDCA)Patients with alkaline phosphatase (ALP) ≥1.67 times the upper limit of normal (ULN) and total bilirubin (TB) ≤2 times ULN. Patients take 10mg of Seladelpar or placebo orally daily (randomized 2:1), for 12 months.Stratification was performed according to the ALP and pruritus Numerical Rating Scale (NRS; 0-10). The primary endpoint was the composite response at Month 12 (defined as ALP <1.67 × ULN, ALP reduction ≥15%, and TB ≤ULN).ASSURE StudyInclude PBC patients who previously participated in seladelpar studies, with a 5-year follow-up to evaluate the long-term safety and efficacy of Seladelpar., and the primary endpoint was adverse events during treatment and biochemical and hematologic results.

Among the 193 PBC patients in the RESPONSE study, 11 were Asian patients (7 received Seladelpar treatment and 4 received placebo), and the remaining 182 patients were non-Asian. At the 12th month of treatment,Composite Response Rate of Seladelpar Treatment in Asian Patients is 100%(7/7), the composite response rate in the placebo group was 0% (0/4); among non-Asian patients, the composite response rate for those treated with Seladelpar was 59.5% (72/121), and 21.3% (13/61) in the placebo group. Among the 174 PBC patients in the ASSURE study, 13 were Asian and the remaining 161 were non-Asian. Follow-up data at the 12th month were available for 8 Asian patients and 140 non-Asian patients, showing thatThe composite response rates for Asian and non-Asian patients treated with Seladelpar 10mg were 75% (6/8) and 70% (98/140), respectively.。

According to the conclusions drawn by the researchers, both the RESPONSE and ASSURE studies demonstrated that seladelpar effectively reduced cholestasis-related biomarkers in Asian or non-Asian PBC patients, with good safety and tolerability.

This timeSeladelpar's submission for clinical trials in China means that the product is expected to commence clinical research in China in the near future.

[1] Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China.Retrieved Apr 15，2025, From https://www.cde.org.cn/main/xxgk/listpage/4b5255eb0a84820cef4ca3e8b6bbe20c

[2]Gilead’s Seladelpar Granted Conditional European Marketing Authorization for the Treatment of Primary Biliary Cholangitis. Retrieved February 21, 2025, from https://www.businesswire.com/news/home/20250213709259/en