Gilead Sciences, Inc. announced two-year interim results from the ongoing ASSURE study of investigational seladelpar for the treatment of primary biliary cholangitis (PBC), a rare, chronic inflammatory liver disease. The two-year interim analysis includes people living with PBC who participated in any prior clinical studies of seladelpar (legacy studies) and participants from the pivotal Phase 3 RESPONSE study. Results demonstrated rapid and sustained improvements in markers of cholestasis, including high rates of normalization of liver biomarkers and a clinically meaningful reduction in pruritus (itch).

These most recent data were shared in a presentation during the European Association for the Study of the Liver (EASL) Congress 2024 in Milan, Italy. ASSURE is an open-label, long-term Phase 3 study evaluating the safety and efficacy profile of seladelpar, a potent, selective, orally active delpar, or selective peroxisome proliferator-activated receptor delta (PPAR) agonist, in adults with PBC. Participants received 10 mg seladelpar, once daily, for up to 155 weeks in the current analysis of the ASSURE cohort.

The two-year interim analysis, with a data cutoff date of January 31, 2024, included 179 participants from legacy studies and 158 participants from the Phase 3 registrational RESPONSE study. Of the 99 participants from legacy studies completing 24 months of treatment with seladelpar, 70% met the composite response endpoint, which includes alkaline phosphatase (ALP) levels below 1.67 x the upper limit of normal (ULN), a decrease in ALP levels of at least 15%, and total bilirubin (TB) levels at or below the ULN. In addition, 42% of these participants achieved ALP normalization at 24 months, a marker of liver disease progression.

For the 164 participants from legacy studies completing 12 months of treatment with seladelpar, 73% achieved the clinically meaningful composite response endpoint, with 42% experiencing ALP normalization. For those participants who completed the 12-month RESPONSE study after randomization to seladelpar, who continued into the ASSURE study and received continuous seladelpar treatment for a total of 18 months (12 months in RESPONSE, six months in ASSURE, n=102), 62% achieved the composite response endpoint, and 33% reached ALP normalization. For participants who received seladelpar for 24 continuous months (n=29), 72% and 17% met the composite response endpoint and ALP normalization, respectively.

Additional study findings demonstrate that of the 52 participants previously randomized to placebo in the RESPONSE study, 75% met the composite response endpoint, and 27% achieved ALP normalization following cross-over to six months of treatment with seladelpar in ASSURE. Following 12 months of treatment, 94% of those crossing over met the composite response endpoint, and 50% reached ALP normalization (n=16). Across all ASSURE participants, the safety profile was favorable and generally well-tolerated with long-term use, with no treatment-related serious adverse events as determined by the study investigators.

These results are similar to the results seen in an earlier data cut presented at Digestive Disease Week last month. Interim results of a subset of participants with liver cirrhosis from the open-label, long-term ASSURE safety study will be shared as an oral presentation at EASL (Presentation ID: OS-019). These participants with compensated cirrhosis, received a second year of seladelpar treatment following their initial participation in the Phase 3 RESPONSE study.

Consistent with the results of the RESPONSE trial, participants achieved clinically meaningful improvements in markers of cholestasis and liver injury. Among participants with compensated liver cirrhosis from legacy studies who enrolled in the ASSURE study (n=35), 91% were female with a mean age of 60.8 years. Additionally, 23% (8/35 participants) had portal hypertension, 89% were Child-Pugh (CP) class A, and 11% were CP-B. At baseline, mean ALP was 245 U/L, TB was 1.0 mg/dL (31% > ULN), and mean liver stiffness measure assessed by FibroScan was 19.9 kPa.

As of the data cutoff date (January 31, 2024), 32 participants with compensated cirrhosis had completed 12 months of treatment. Of those participants, 56% (18/32) met the composite biochemical endpoint at Month 12, with ALP normalization occurring in 47% (15/32 participants). No serious adverse events were related to the study drug as determined by the study investigators.

A New Drug Application (NDA) for seladelpar for the treatment of primary biliary cholangitis, including pruritus, in adults without cirrhosis or with compensated cirrhosis (Child-Pugh A) who are inadequate responders or intolerant to ursodeoxycholic acid (UDCA), has been accepted for priority review by the U.S. Food and Drug Administration (FDA) with an anticipated decision in August 2024. The U.K. Medicines and Healthcare Products Regulatory Agency (MHRA) and the European Medicines Agency (EMA) have also accepted seladelpar for review. ASSURE is an open label study to evaluate the long-term safety and tolerability of seladelpar in people with primary biliary cholangitis (PBC) who have already participated in other PBC clinical trials of seladelpar.

The study is currently enrolling up to 500 people living with PBC from across 160 sites around the world. ASSURE will also assess the long-term efficacy of seladelpar and its impact on important patient reported outcomes such as cholestatic pruritis, or itch, which can have a significant impact on the quality of life of people living with PBC. Participants enrolled in ASSURE at the time of this interim data analysis include participants from previous studies of seladelpar in PBC, including the Phase 3 registrational RESPONSE study and the other clinical trials, which include the Phase 2 dose-ranging study, the Phase 3/4 long-term open label study and the Phase 3 ENHANCE program that were both terminated early, and the ongoing open label study in people with PBC and hepatic impairment.

The majority of participants from the legacy studies have a gap of one year or more off-treatment before enrollment in the study, and 19% of participants had cirrhosis. Participants received an open-label daily dose of 10 mg of seladelpar orally for up to 155 weeks in ASSURE.