Is Livdelzi (Seladelpar) on the market?

Livdelzi (Seladelpar) is a peroxisome proliferator-activated receptor (PPAR)-delta agonist. Seladelpar is a single enantiomer in the R-configuration. On August 14, 2024, seladelpar received accelerated approval from the U.S. Food and Drug Administration (FDA) for the treatment of primary biliary cholangitis (PBC), a disease associated with abnormal bile acid metabolism. Livdelzi blocks bile acid synthesis.

The FDA's decision was based on reductions in alkaline phosphatase (ALP), a key result from a placebo-controlled Phase 3 response study that compared Livdelzi 10 mg once daily (n=128) to placebo (n=65) for 12 months. Based on response results, 62% of patients treated with Livdelzi versus 20% of patients treated with placebo met the primary endpoint of composite biochemical response at month 12, defined by reductions in ALP (ALP <1.67 times the upper limit of normal, with at least a 15% reduction from baseline) and total bilirubin (upper limit of normal). Additionally, at this time point, 25% of patients receiving Livdelzi achieved normalization of ALP values, which was not observed in patients receiving placebo.

Additionally, patients treated with Livdelzi showed a "statistically significant reduction in pruritus" at 6 months. Common adverse events reported by at least 5% of patients treated with Livdelzi included headache, abdominal pain, nausea, bloating, and dizziness; however, no treatment-related serious adverse events were reported.

Livdelzi is only indicated for the treatment of PBC disease by reducing alkaline phosphatase, and has not been reported to improve survival or prevent hepatic decompensation events. Continued approval for this indication "may be contingent on verification and characterization of clinical benefit in confirmatory trials."