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
'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
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
'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.
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 NRS4, 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 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 (
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
About ASSURE (NCT03301506)
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.
Interim results of ASSURE (Abstract #LB-283), titled 'Long-term efficacy and safety of open-label seladelpar treatment in patients with primary biliary cholangitis (PBC): Interim results for 2 years from the ASSURE study,' will be presented Dr.
About Seladelpar
Seladelpar, an investigational treatment for people with PBC, is a first-in-class oral, selective PPAR-delta agonist, or delpar. PPAR-delta has been shown to regulate critical metabolic and liver disease pathways. Preclinical and clinical data support its ability to regulate genes involved in bile acid synthesis, inflammation, fibrosis and lipid metabolism, storage, and transport. Seladelpar is not approved by the FDA or any other regulatory authority globally and has not been determined to be safe or efficacious for any use.
About PBC
PBC is a rare, chronic inflammatory liver disease primarily affecting women (1 in 1,000 women over the age of 40 or about 130,000 total people in the
About CymaBay
About
For decades, Gilead has pioneered the way forward to improve the lives of people living with liver disease around the world. We have helped to transform hepatitis C from a chronic condition into one that can be cured for millions of people. For people living with hepatitis B or D, our focus on advancing our medicines drives hope that today's research will turn into tomorrow's cures. Beyond viral hepatitis, we're working to deliver advanced treatments for people living with primary biliary cirrhosis (PBC). But our commitment doesn't stop there. Through our ground-breaking science and collaborative partnerships, we strive to create healthier futures for everyone living with liver disease. We are committed to a future without liver disease.
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Forward-Looking Statements
This press release includes forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the ability of Gilead and CymaBay to initiate, progress or complete clinical trials within currently anticipated timelines or at all, and the possibility of unfavorable results from ongoing or additional clinical studies, including those involving seladelpar (such as the ASSURE and RESPONSE trials); uncertainties relating to regulatory applications and related filing and approval timelines, including the risk that the FDA and other regulatory authorities may not approve seladelpar for the treatment of PBC, and the risk that any such approvals, if granted, may be subject to significant limitations on use; the possibility that Gilead and CymaBay may make a strategic decision to discontinue development of programs for indications that are currently under evaluation and, as a result, these programs may never be successfully commercialized for such indications and any assumptions underlying any of the foregoing. These and other risks, uncertainties and factors are described in detail in Gilead's Quarterly Report on Form 10-Q for the quarter ended
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