PRO-C3 may illuminate liver disease progression in PBC

The findings, which came from extended follow-up of the phase 3 ELATIVE trial of elafibranor, a peroxisome proliferator-activated receptor (PPAR)-alpha/delta agonist, and were presented at AASLD The Liver Meeting in Washington, DC, USA, also support previous evidence that the drug stabilizes hepatic fibrosis in PBC patients.

PRO-C3 testing is still not commonly used in PBC, study co-author Nuno Antunes (Ipsen, Cambridge, Massachusetts, USA) told medWireNews. “It’s still a very experimental marker,” he said, although it is “broadly used in other indications” and “provides complementary information” on disease status.

Antunes envisages that it could be used alongside other markers to monitor the patient, which together would build a picture “from different lenses” of how the patient’s liver is responding to treatment.

He continued: “Each of the tests that we use in clinical practice have strengths and weaknesses. At the end of the day, the more complete a picture you can get of a process that is very complex, that involves multiple pathways, that will help you.

“So maybe you would not make a decision based on individual PRO-C3 results, but you see it in the context of the full clinical picture of the patient.”

Fifty-two-week results from ELATIVE led to the approval of elafibranor as a second-line treatment in patients with PBC.

For the current analysis, Christopher Bowlus (UC Davis School of Medicine, Sacramento, California, USA) and colleagues assessed changes in PRO-C3 levels out to week 156 of the trial, in which patients were randomly assigned to receive once-daily elafibranor 80 mg or placebo for a minimum of 52 weeks, after which they could enter an open-label extension (OLE) phase.

At the data cutoff in June 2024, 108 patients had started on elafibranor in the double-blind period (DBP) and continued on the drug, while 45 of 52 patients originally started on placebo switched to elafibranor for the OLE.

The results show that, from baseline to week 52, PRO-C3 levels decreased by an average of 3.9 µg/L in the elafibranor group, while they increased by 2.8 µg/L in the placebo group. In the OLE, patients who started on elafibranor saw their PRO-C3 levels maintained or further decreased out to week 156, while patients crossing over from the placebo group had “a decrease from baseline of similar magnitude to that in patients on elafibranor during the DBP,” the team reports.

Further analysis indicated that there was a moderate correlation between PRO-C3 levels and enhanced liver fibrosis scores, as well as between PRO-C3 and liver stiffness measurement, ranging from a Spearman’s correlation coefficient of 0.59 to 0.69. There was, however, a weaker correlation between PRO-C3 levels and the blood biomarkers alkaline phosphatase and total bilirubin.

“Assessment of continued treatment with elafibranor in the ongoing OLE would be needed to determine the relationship between these noninvasive tests and clinical outcomes,” the researchers note.