RESPONSE Biochemical Results

LIVDELZI achieved statistically significant reduction in biochemical response1

The primary endpoint was biochemical response at month 12, where biochemical response was defined as achieving alkaline phosphatase (ALP) less than 1.67-times upper limit of normal (ULN), ALP decrease of greater than or equal to 15% from baseline, and total bilirubin (TB) less than or equal to ULN.1

The ULN for ALP was defined as 116 U/L. The ULN for TB was defined as 1.1 mg/dL.1

Bar chart illustration showing the results of the RESPONSE trial: 62%, or 79 of 128 patients in the LIVDELZI arm versus 20%, or 13 of 65 patients in the placebo arm achieved a complete response at month 12. The P value of the difference between groups was <0.0001.Bar chart illustration showing the results of the RESPONSE trial: 62%, or 79 of 128 patients in the LIVDELZI arm versus 20%, or 13 of 65 patients in the placebo arm achieved a complete response at month 12. The P value of the difference between groups was <0.0001.

In the trial, there were 12 patients (6%) who were intolerant to ursodeoxycholic acid (UDCA) and initiated treatment as monotherapy: 8 patients (6%) in the LIVDELZI 10 mg arm and 4 patients (6%) in the placebo arm.1

62% of patients treated with LIVDELZI achieved the composite biochemical response by month 12 (vs 20% of patients in the placebo arm P<0.0001)1,2

Rapid and sustained reduction in ALP from baseline1

Secondary endpoint: Mean reduction in ALP

The figure below shows the mean (95% confidence interval) levels of ALP over 12 months. There was a trend of lower ALP in the LIVDELZI arm compared to the placebo arm starting at month 1 through month 12.1

A line graph entitled ALP Change From Baseline showing both the LIVDELZI 10 mg ± UDCA and the placebo treatment arm over a period of 12 months. At 12 months, the ALP change from baseline was ~42% for LIVDELZI 10 mg ± UDCA, and ~4% for placebo ± UDCA.A line graph entitled ALP Change From Baseline showing both the LIVDELZI 10 mg ± UDCA and the placebo treatment arm over a period of 12 months. At 12 months, the ALP change from baseline was ~42% for LIVDELZI 10 mg ± UDCA, and ~4% for placebo ± UDCA.

In the trial, there were 12 patients (6%) who were intolerant to UDCA and initiated treatment as monotherapy: 8 patients (6%) in the LIVDELZI 10 mg arm and 4 patients (6%) in the placebo arm.1

Mean ALP reduction at months 1, 3, 6, 9, and 12 were secondary endpoints. For these endpoints, multiplicity was not controlled.

~42% reduction in ALP at month 12 (vs ~4% in the placebo arm), with ~36% reduction achieved at month 1 (vs ~5% in the placebo arm)2,3

LIVDELZI monotherapy1

Biochemical response at month 3 comparing LIVDELZI as a monotherapy to placebo was evaluated in a pooled analysis of a subset of patients from RESPONSE and another randomized, double-blind, placebo-controlled trial in a similar patient population. There was a trend of improvement on biochemical response at month 3 in the LIVDELZI monotherapy group compared to the placebo group.

The only PBC treatment that has shown ALP normalization in 1 out of 4 patients in 12 months1

Key secondary endpoint: ALP normalization1

ALP normalization (ie, ALP less than or equal to ULN) at month 12 was a key secondary endpoint.

Bar chart depicting the secondary endpoint of ALP normalization (ALP ≤1.0 times the upper limit of normal) at month 12. In this chart, 25%, or 32 out of 128 patients in the LIVDELZI 10 mg ± UDCA arm achieved ALP normalization, compared with no patients in the placebo arm. The P value of the difference between groups was <0.0001.Bar chart depicting the secondary endpoint of ALP normalization (ALP ≤1.0 times the upper limit of normal) at month 12. In this chart, 25%, or 32 out of 128 patients in the LIVDELZI 10 mg ± UDCA arm achieved ALP normalization, compared with no patients in the placebo arm. The P value of the difference between groups was <0.0001.

In the trial, there were 12 patients (6%) who were intolerant to UDCA and initiated treatment as monotherapy: 8 patients (6%) in the LIVDELZI 10 mg arm and 4 patients (6%) in the placebo arm.1

25% of patients treated with LIVDELZI achieved ALP normalization at month 12 (P<0.0001)1
References: 1. LIVDELZI [prescribing information]. Foster City, CA: Gilead Sciences, Inc.; 2024. 2. Hirschfield GM, Bowlus CL, Mayo MJ, et al. A phase 3 trial of seladelpar in primary biliary cholangitis. N Engl J Med. 2024;390(9):783-794. doi:10.1056/NEJMoa2312100 3. Data on file. Gilead Sciences, Inc.; 2024.