Seladelpar demonstrated a sustained and consistent long term efficacy and safety profile in primary biliary cholangitis – Gilead Sciences

Gilead Sciences, Inc., following the recent acquisition of CymaBay Therapeutics, 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 III 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.

“The data presented at EASL further support the sustained efficacy and safety profile of seladelpar observed across its robust development program, including a capacity to normalize ALP values for many of the people studied with PBC. Given ALP is recognized as an important surrogate marker of disease progression in PBC, providers are shifting to normalization as a treatment goal, which could potentially be enabled by seladelpar, if approved,” said Dr, Timothy Watkins, Vice President, Clinical Development of Inflammation Therapeutics, Gilead Sciences. “Seladelpar is a potential best-in-class therapy that could transform the treatment landscape for people living with PBC by not only improving or even normalizing markers of liver function, but also improving pruritis or itch. Pruritis is a particularly burdensome symptom of PBC which can significantly disrupt a person’s quality of life. We’re committed to transforming the management of PBC and the lives of those impacted by this rare disease as we work together to bring seladelpar to the community, if approved.”

ASSURE is an open-label, long-term Phase III 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.

Patient-reported pruritus was also collected throughout the ASSURE study using the numerical rating scale (NRS; 0-10). Among the participants with baseline NRS?4, sustained improvement in pruritus was observed with a mean reduction of 3.8 and 3.1 points at 12 and 24 months in participants from legacy studies, respectively. For RESPONSE participants, a mean reduction of 3.8 was observed in both continuous and former placebo participants at six months in the ASSURE study. These findings were consistent with the results observed in the pivotal RESPONSE study, reinforcing the durability of this treatment effect.

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 III 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.

“Currently, there is no cure for PBC. While there are lifelong medicines that may slow liver damage and stop it from progressing, current medications fall short in about 40% of people. This is because many individuals continue to have abnormal liver tests on the current treatment options, and these treatments don’t reduce one of the main relentless symptoms, pruritis, which impacts the quality of life in people living with PBC,” said Dr. Palak Trivedi, Associate Professor and Consultant Hepatologist, University of Birmingham, and presenter of the study. “The long-term efficacy and safety interim results from ASSURE demonstrate that seladelpar may meaningfully raise the bar in PBC. Seladelpar can help people achieve significant reduction, and in some cases, normalization of liver blood tests. At the same time, seladelpar can also help lower itch intensity..