Intercept Presents New Phase 3 POISE Data on OCA's Impact on Liver Biomarkers in PBC Patients at EASL Congress 2024
On June 4, 2024, Intercept Pharmaceuticalss, a subsidiary of Alfasigma S.p.A., revealed promising new data from its Phase 3 POISE trial on obeticholic Acid (OCA) at the European Association for the Study of the Liver (EASL) Congress in Milan, Italy. The findings highlight OCA’s impact on various liver biomarkers in patients with primary biliary cholangitis (PBC).
Reduction in Key Liver Biomarkers
The POISE trial's intention-to-treat (ITT) population demonstrated significant reductions in alanine aminotransferase (ALT) and aspartate aminotransferase (AST), crucial liver enzymes linked to adverse clinical outcomes. These reductions were noticeable as early as the second week of treatment and continued throughout the study. By the sixth month, over half of the patients with elevated ALT at baseline showed normalization, while nearly a third of those with elevated AST saw similar improvements.
Enhanced Liver Fibrosis and Inflammatory Biomarkers
Additional analyses examined the effects of OCA on liver fibrosis and inflammation. Noninvasive tests such as enhanced liver fibrosis (ELF), transient elastography (TE), aminotransferase to platelet ratio index (APRI), and fibrosis-4 (FIB-4) index showed that OCA treatment stabilized liver fibrosis over time, regardless of baseline severity. Specifically, the ELF and TE measures remained stable over 24 months, indicating that OCA could delay fibrosis progression.
POISE Trial Structure and Findings
The POISE trial included 217 patients randomized into three groups: placebo, OCA 5 mg with an option to titrate to 10 mg, and OCA 10 mg daily. The study had a 12-month double-blind phase and an extension phase lasting up to five years. Significant improvements in ALT and AST were observed in the OCA groups compared to the placebo group. For instance, among patients with baseline ALT levels above 41 U/L, 55% on OCA titration and 53% on OCA 10 mg showed normalization by month six, compared to only 16% in the placebo group.
Furthermore, the trial assessed OCA’s impact on inflammatory and immune biomarkers. The data indicated that OCA substantially increased the proportion of PBC patients achieving normalized levels of tumor necrosis factor alpha (TNFα), high-sensitivity C-reactive protein (hsCRP), and immunoglobulin M (IgM), correlating with improved clinical outcomes.
Expert Commentary
Dr. Robert G. Gish from Loma Linda University emphasized the importance of understanding the multifaceted nature of PBC to tailor treatments effectively. He highlighted the potential of OCA to stabilize liver fibrosis, suggesting early treatment could prevent further disease progression.
Safety and Efficacy
The study affirmed the safety and efficacy of OCA for PBC patients who did not respond adequately to or could not tolerate ursodeoxycholic acid (UDCA). Among the 198 patients who completed the double-blind phase, over 95% continued into the long-term safety extension phase. The analyses showed that OCA helped stabilize liver enzymes and inflammation markers over an extended period, which could minimize the risk of disease progression.
Conclusion
The new data from the POISE trial presented at EASL offers compelling evidence that OCA can significantly improve liver health in PBC patients by reducing crucial liver biomarkers and stabilizing fibrosis. These findings suggest that early intervention with OCA could be beneficial in managing PBC and preventing its progression. Intercept Pharmaceuticals continues to enhance the understanding of PBC treatment responses, contributing valuable insights to the medical community.
### About Primary Biliary Cholangitis
Primary biliary cholangitis (PBC) is a rare autoimmune liver disease mostly affecting women over 40. It leads to bile duct inflammation and fibrosis, potentially resulting in cirrhosis or liver failure if untreated.
### About Obeticholic Acid
Obeticholic acid (OCA) is a farnesoid X receptor (FXR) agonist used to treat PBC in patients who do not respond adequately to UDCA. It is approved under accelerated approval based on reducing alkaline phosphatase (ALP) levels, although its long-term benefits are still being assessed.
### Safety Information
OCA has been associated with severe hepatic events, particularly in patients with cirrhosis. It is contraindicated in patients with decompensated cirrhosis, compensated cirrhosis with portal hypertension, or complete biliary obstruction. Regular monitoring and potential discontinuation are advised for patients showing signs of hepatic decompensation or severe pruritus.
With advancements like these, Intercept Pharmaceuticals aims to continually improve the management and treatment of rare liver diseases like PBC.
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