Gilead Highlights New Two-Year Data for Seladelpar Before FDA Decision

Gilead Sciences has released additional long-term data supporting the efficacy of seladelpar as a potential treatment for primary biliary cholangitis (PBC) ahead of a crucial U.S. approval decision anticipated in mid-August. The new findings from the ASSURE trial were presented at the European Association for the Study of the Liver (EASL) congress, demonstrating the continued benefits of the oral PPAR-delta agonist, which Gilead acquired through a recent $4.3-billion acquisition of CymaBay.

Timothy Watkins, head of clinical development for inflammation therapeutics at Gilead, stated that the data presented at EASL solidify the sustained efficacy and safety profile of seladelpar observed across its development program, highlighting its potential to normalize alkaline phosphatase (ALP) values. "Seladelpar is a potential best-in-class therapy that could transform the treatment landscape for people living with PBC," he noted.

The open-label ASSURE study is enrolling up to 500 patients who have previously participated in other clinical trials of seladelpar, including the pivotal RESPONSE trial. The two-year interim analysis, based on data from 179 participants as of January 31, reveals promising outcomes.

Key findings show that 70% of the 99 participants from prior studies who completed 24 months of seladelpar treatment achieved their target goals consistently. Similarly, data from 20 patients presented by Gilead last month also indicated a steady 70% success rate. The composite response endpoint includes having ALP levels below 1.67 times the upper limit of normal (ULN), reducing ALP levels by 15% or more, and having total bilirubin levels at or below ULN. Additionally, 42% of these patients achieved ALP normalization at 24 months.

For the 102 patients who completed the RESPONSE study and then continued in ASSURE for an additional six months, totaling 18 months of continuous seladelpar treatment, 62% met the composite response endpoint, and 33% achieved normal ALP levels. Among 29 patients treated continuously for two years, 72% met the composite response endpoint, and 17% achieved normal ALP levels.

A subset of ASSURE patients with compensated liver cirrhosis also showed significant improvements in markers of cholestasis and liver injury after receiving seladelpar for a second year. Among 32 participants from legacy studies, 56% met the composite biochemical endpoint at 12 months, and 47% saw their ALP levels normalize, without serious treatment-related adverse events.

Moreover, patients with PBC experiencing a baseline NRS≥4 level of pruritus reported a sustained reduction in itch over time. There was an average decrease of 3.8 points at 12 months and 3.1 points at 24 months among participants from legacy studies. For RESPONSE participants, a mean reduction of 3.8 points was observed in both continuous and former placebo participants at six months in the ASSURE study.

Presenter Palak Trivedi emphasized that current medications fall short for about 40% of PBC patients, as many continue to have abnormal liver tests and persistent pruritus. Seladelpar, however, may significantly improve treatment outcomes for PBC patients.

In related news, the FDA is set to decide on Ipsen and Genfit's oral PPAR-alpha/delta agonist elafibranor for PBC on June 10. New data from the Phase III ELATIVE trial presented at EASL show that 70% of patients treated with elafibranor achieved a composite endpoint of slowing disease progression, as measured by biochemical response, after 78 weeks.