Elafibranor significantly improved key markers of disease activity compared with placebo, supporting ALP normalization as an achievable treatment goal for patients with PBC who have an incomplete response or intolerance to first-line therapy.
ALEXANDRIA, Va. — Nov. 5, 2026 — The American Association for the Study of Liver Diseases (AASLD) today announced the publication of positive Phase III ELSPIRE trial results in its flagship journal, HEPATOLOGY. The study evaluated elafibranor, a peroxisome proliferator-activated receptor (PPAR)-α/δ agonist, as a second-line treatment for patients with primary biliary cholangitis (PBC) who have persistently elevated alkaline phosphatase (ALP) levels despite treatment with, or intolerance to, ursodeoxycholic acid (UDCA).
The study will be presented as a Late-Breaking Abstract at The Liver Meeting® 2026 in Denver, CO on November 8, 1-2PM MT in the poster hall.
PBC is a chronic, progressive autoimmune liver disease characterized by the destruction of small bile ducts within the liver. This damage disrupts the normal flow of bile, leading to its accumulation and causing inflammation, liver injury, and fibrosis. Over time, the disease can progress to cirrhosis and, in advanced cases, liver failure.
While ALP below 1.67× the upper limit of normal (ULN) is considered an adequate treatment response for PBC, elevated ALP remains associated with disease progression and reduced transplant-free survival. ALP normalization is linked to better long-term outcomes, supporting more ambitious treatment goals.
The phase III randomized controlled ELSPIRE trial enrolled patients with PBC and persistently elevated ALP despite UDCA treatment or intolerance. The trial met its primary endpoint, with 85.3% of elafibranor-treated patients achieving ALP normalization at Week 52 versus 23.3% receiving placebo (p<0.0001). Elafibranor also significantly improved biochemical response and was well tolerated, with no new safety signals.
"These findings represent an important advancement in our understanding of treatment goals for patients living with PBC," said Kris V. Kowdley, MD, AGAF, FAASLD, FACG, FACP, Liver Institute Northwest, Velocity Clinical Research and Washington State University. "While traditional measures of treatment response have focused on reducing ALP below 1.67 times the upper limit of normal, growing evidence suggests that achieving normal ALP levels may be associated with better long-term outcomes. The results of this study demonstrate that ALP normalization is an achievable goal for a substantial proportion of patients receiving Elafibranor, even among those with moderately elevated ALP levels."
Key findings at Week 52 included:
- ALP normalization: 85.3% of patients receiving Elafibranor achieved normal ALP levels, compared with 23.3% receiving placebo (p<0.0001).
- Reduction in ALP: Elafibranor demonstrated a least squares mean ALP reduction of 36.5% from baseline, compared with a 4.2% reduction with placebo (p<0.0001).
- Additional biochemical improvements: A greater proportion of patients receiving Elafibranor achieved ALP normalization accompanied by at least a 15% reduction from baseline.
- Complete biochemical response: More patients treated with Elafibranor achieved normalization across multiple liver-related laboratory measures, including ALP, total bilirubin, transaminases, albumin, and international normalized ratio (INR).
- Safety and tolerability: Elafibranor was well tolerated over the 52-week treatment period, with no new safety signals identified.
"These results underscore the potential of Elafibranor to raise the standard of biochemical response in PBC," said Naga P. Chalasani, MD, FAASLD, incoming Co-Editor-in-Chief of HEPATOLOGY. "We are delighted to publish these important findings in HEPATOLOGY. The results provide valuable new insights that advance our understanding of PBC and have the potential to inform future research and clinical practice. We are excited to share this work with the hepatology community."
For additional information on PBC, explore these AASLD resources:
- New! Explore the Clinical Practice Guideline on Management of Primary Biliary Cholangitis from AASLD and AGA
- New! A Phase 2b/3 Trial of Saroglitazar in Primary Biliary Cholangitis
- AASLD Cholestatic and Autoimmune Liver Diseases Special Interest Group
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About AASLD
The American Association for the Study of Liver Diseases (AASLD) is the leading organization of scientists and health care professionals committed to preventing and curing liver disease. AASLD fosters research that leads to improved treatment options for millions of liver disease patients and advances the science and practice of hepatology through educational conferences, training programs, professional publications, and partnerships with government agencies and sister societies.
About HEPATOLOGY
The premier publication in the field of liver disease, HEPATOLOGY publishes original, peer-reviewed articles concerning all aspects of liver structure, function, and disease. Each month, the distinguished Editorial Board monitors and selects only the best articles on subjects such as immunology, chronic hepatitis, viral hepatitis, cirrhosis, genetic and metabolic liver diseases and their complications, liver cancer, and drug metabolism. Follow the journal on X at @HEP_Journal.
About The Liver Meeting®
TLM is the premier global event in hepatology, bringing together the researchers, clinicians, advanced practice providers, specialists, and leaders shaping the future of liver care. Through cutting-edge science, practical education, and meaningful collaboration, attendees gain the knowledge and tools needed to address today's most pressing challenges in hepatology. With expert-led sessions, innovative exhibits, and unmatched networking opportunities, TLM empowers professionals across every career stage to advance patient care and research to elevate the standard of liver health worldwide. Learn more about TLM26 at www.aasld.org/tlm-26.
About Elafibranor
Elafibranor is a PPAR-α/δ agonist being evaluated as a second-line treatment for patients with PBC. By targeting pathways involved in bile acid metabolism, inflammation, and liver disease, Elafibranor has demonstrated improvements in biochemical markers of PBC in clinical studies.