Potential First-Line Treatment?
In Dr. Assis’ view, the RESPONSE trial, coupled with the recently reported ELATIVE trial of the dual PPAR-alpha and PPAR-delta agonist elafibranor in PBC, “cement the role of PPAR agonists as the preferred second-line treatment in primary biliary cholangitis.”
“The reduction in serum cholestatic markers and the safety profiles of elafibranor and seladelpar offer clear advantages beyond what was previously shown with obeticholic acid. These trials also cement a new treatment goal for primary biliary cholangitis in which a reduction in pruritus should be expected as part of anticholestatic treatment,” Dr. Assis wrote.
“The results of these trials suggest that the use of PPAR agonists in primary biliary cholangitis could improve treatment outcomes while also improving quality of life, which is a highly desirable alignment of clinician and patient goals,” Dr. Assis added.
Looking ahead, Dr. Hirschfield sees a potential role for seladelpar earlier in the course of PBC treatment, he said in an interview.
“Over time, the way we treat patients will not be to wait to fail. It will be treat to target and treat to success,” Dr. Hirschfield said.
Earlier this month, the US Food and Drug Administration accepted CymaBay Therapeutics’ new drug application for seladelpar for the treatment of PBC, including pruritus in adults without cirrhosis or with compensated cirrhosis (Child Pugh A) who fail to respond adequately or cannot tolerate UDCA. Seladelpar for PBC was granted breakthrough designation in October 2023.
The study was funded by CymaBay Therapeutics. Disclosures for authors and editorialist are available at NEJM.org.
A version of this article appeared on Medscape.com.