Gilead's Seladelpar Demonstrates Sustained Long-Term Efficacy and Safety in Primary Biliary Cholangitis
Positive Two-Year Interim Results Consistent with One-Year Findings in Phase 3 RESPONSE Study Participants
Rapid and Lasting Reduction in Patient-Reported Pruritus (Itching) Observed in Those with Moderate to Severe Symptoms
Significant Improvements in Cholestasis and Liver Injury Markers Noted in Participants with Compensated Cirrhosis
Gilead, which recently acquired CymaBay Therapeutics, has announced promising two-year interim results from the ongoing ASSURE study of seladelpar, an investigational treatment for primary biliary cholangitis (PBC), a rare chronic inflammatory liver disease. The analysis includes participants from previous seladelpar studies and the pivotal Phase 3 RESPONSE study. The results highlight rapid and sustained improvements in cholestasis markers and a meaningful reduction in pruritus.
The ASSURE study is an open-label, long-term Phase 3 trial assessing the safety and efficacy of seladelpar, a potent, selective oral PPAR delta agonist, in adults with PBC. Participants received 10 mg of seladelpar daily for up to 155 weeks. The interim analysis, with a data cutoff of January 31, 2024, included 179 participants from legacy studies and 158 from the Phase 3 RESPONSE study.
Among the 99 participants from legacy studies who completed 24 months of treatment, 70% met the composite response endpoint, which involves alkaline phosphatase (ALP) levels below 1.67 times the upper limit of normal (ULN), a reduction in ALP levels of at least 15%, and total bilirubin (TB) levels at or below the ULN. Additionally, 42% of these participants achieved ALP normalization at 24 months, indicating a halt in liver disease progression. For the 164 participants from legacy studies completing 12 months of treatment, 73% met the composite response endpoint, with 42% achieving ALP normalization.
Participants who completed the 12-month RESPONSE study and continued into ASSURE for a total of 18 months showed 62% achieving the composite response endpoint, and 33% reached ALP normalization. Those on seladelpar for 24 continuous months had 72% meeting the composite endpoint, and 17% normalized ALP. Among participants previously randomized to placebo in RESPONSE, 75% met the composite endpoint, and 27% achieved ALP normalization after crossing over to seladelpar in ASSURE. Following 12 months of treatment, 94% of the crossover group met the composite endpoint, with 50% normalizing ALP. The safety profile of seladelpar was favorable and well-tolerated over long-term use, with no serious adverse events related to treatment, consistent with earlier data from Digestive Disease Week.
Pruritus, reported by participants, was measured using the numerical rating scale (NRS; 0-10). Among those with baseline NRS≥4, sustained improvement was seen with a mean reduction of 3.8 points at 12 months and 3.1 points at 24 months in legacy study participants. For RESPONSE participants, a mean reduction of 3.8 points was observed at six months in ASSURE, aligning with RESPONSE study results and affirming the treatment's long-term effectiveness.
A subset analysis of participants with compensated cirrhosis in the ASSURE study will be presented at EASL. These participants, who continued seladelpar treatment after the Phase 3 RESPONSE study, showed significant improvements in cholestasis and liver injury markers. Among the 35 participants with compensated cirrhosis from legacy studies in ASSURE, 91% were female with an average age of 60.8 years. At baseline, the mean ALP was 245 U/L, TB was 1.0 mg/dL, and the mean liver stiffness measure was 19.9 kPa. After 12 months, 56% met the composite biochemical endpoint, and 47% achieved ALP normalization. No serious adverse events were linked to the study drug.
The U.S. Food and Drug Administration (FDA) has accepted a New Drug Application (NDA) for seladelpar for the treatment of PBC in adults without cirrhosis or with compensated cirrhosis who are inadequate responders or intolerant to ursodeoxycholic acid (UDCA), with an expected 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.
Comments