How effective is Livdelzi (Seladelpar)?

Interim results from the ASSURE study show that treatment with the investigational PPARdelta agonist Livdelzi (Seladelpar) improves markers of cholestasis and reduces inflammation. Other findings suggest that Livdelzi helps reduce itching in patients with primary cholangitis (PBC). There is currently no treatment for PBC-related pruritus.

ASSURE is an open-label study evaluating the long-term safety and efficacy of Livdelzi, a once-daily, potent and selective peroxisome proliferator-activated receptor (PPAR) delta agonist. Ensuring recruitment of adult PBC patients who had previously participated in the Livdelzi study, for which key eligibility criteria included an inadequate response to or intolerance to ursodeoxycholic acid (UDCA), was ensured. This interim data analysis does not include patients from the Phase 3 response study, which will be reported separately. Of the 174 patients included, most had a gap of one year or more between completing their respective primary studies (sLivdelzi or placebo) and entering ASSURE. Enrolled patients received an open-label oral dose of 10 mg Livdelzi once daily, with the majority (97%) also receiving UDCA.

The majority of patients enrolled inASSURE are women (94%), with an average age of 59 years. Baseline characteristics included mean alkaline phosphatase (ALP) 270.5 U/L and total bilirubin (TB) 0.75 mg/dL; 19% of enrolled patients met criteria for cirrhosis. The study evaluated several prespecified biochemical endpoints, including a composite response of alkaline phosphatase (ALP) below 1.67 times the upper limit of normal (ULN), a decrease in ALP of at least 15%, and total bilirubin (TB) below the ULN.

Endpoints were assessed during the study's interim observation period, in which the majority (85%) received at least 12 months of continuous treatment with Livdelzi. Seventy percent of the 148 patients who completed 12 months of treatment achieved the clinically meaningful composite response endpoint. Among patients treated with Livdelzi, 37% experienced normalization of ALP, with a mean ALP change of -44% (-144.4 U/L). Of the 20 patients who completed 24 months of treatment, 70% achieved the composite response endpoint and 25% experienced ALP normalization. Livdelzi also reduced other important biomarkers of liver injury, including TB, gamma-glutamyl transferase (GGT), and alanine aminotransferase (ALT) levels, by 9%, 36%, and 25% respectively from baseline levels.

The study determined that there were no serious adverse events related to treatment in this study. Livdelzi was generally well tolerated, with 4.6% of patients discontinuing treatment due to adverse events. Numerical rating scales (NRS; 0-10) were used throughout the study. In 60 patients with moderate to severe pruritus and an NRS score of ≥4 at baseline, rapid improvement in pruritus was observed at month 1. By month 6, patients reported an average decrease of 3.5 points, and this effect persisted through month 12.