The phase 3 RESPONSE trial assessed the longer-term safety of seladelpar, a novel selective PPAR agonist. The results presented at the AASLD Liver Meeting showed that 5-year safety was similar to placebo in patients with primary biliary cholangitis (PBC.
Researchers pooled data from six studies that assessed seladelpar 10 mg for the treatment of PBC: two placebo-controlled trials and four open-label studies.
At data cutoff (Jan. 31, 2024), 486 patients were treated with seladelpar:
- 355 for ≥1 years;
- 170 for ≥2 years;
- 66 for ≥3 years;
- 36 for ≥4 years; and
- 10 for ≥5 years.
For comparison, 152 patients were treated with placebo: 117 were treated for 12 weeks or longer, 84 for at least 6 months, and 57 for 12 months.
The exposure-adjusted incidence per 100 patient-years for the seladelpar versus placebo groups was:
- 48.3 versus 132.0 adverse events;
- 9.8 versus 12.2 grade 3 and above adverse events;
- 8.0 versus 7.8 serious adverse events; and
- 6.1 versus 13.3 liver-related adverse events.
Muscle, renal, and pancreatic adverse events occurred in less than seven patients per 100 patient-years in the seladelpar group.
Adverse events resulted in treatment discontinuation in 2.9 patients per 100 patient-years in the seladelpar group and 5.6 per 100 patient-years in the placebo cohort.
“Analysis of a large safety database for seladelpar in PBC patients with exposure through 5 years indicated that seladelpar was well tolerated with a safety profile similar to placebo,” the authors concluded.
Reference
Trivedi P, Gordon S, Gulamhusein A, et al. Long-term safety of seladelpar 10 mg with up to 5 years of treatment in patients with primary biliary cholangitis. Abstract 4341. Presented at the 2024 American Association for the Study of Liver Diseases’ 75th Liver Meeting; November. 15–19, 2024; San Diego.
