P3492 - Stabilization of Enhanced Liver Fibrosis and Liver Stiffness Measures in the Open-Label Extension of the Phase 3 POISE Trial of Obeticholic Acid for the Treatment of Primary Biliary Cholangitis
Robert G. Gish, MD1, Darren Wheeler , PhD2, Jing Li, PhD2, Christopher Gasink, MD2, Alan Bonder, 3 1Robert G. Gish Consultants, LLC, San Diego, CA; 2Intercept Pharmaceuticals, Inc., Morristown, NJ; 3Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
Introduction: Transient elastography (TE) noninvasively measures liver stiffness and indirectly evaluates fibrosis. Enhanced liver fibrosis (ELF) assesses 3 blood-based fibrosis markers and is a well-validated measure of fibrosis. We report the results from a post hoc analysis of the impact of obeticholic acid (OCA), an approved treatment for primary biliary cholangitis (PBC), on ELF and TE in patients (pts) from the 5-year open-label extension (OLE) of POISE, a 12-month (M), randomized, double-blind (DB), placebo (PBO)-controlled phase 3 study.
Methods: Pts were randomized to receive PBO, OCA 5–10 mg, or OCA 10 mg daily in the DB phase. During the OLE, all pts were initially treated with OCA 5 mg daily for 3M, after which the dose could be titrated based on response and tolerability. ELF was assessed at baseline (BL) and each year after OCA initiation, using an algorithm based on hyaluronic acid, type III procollagen peptide, and tissue inhibitor of metalloproteinase I levels. Liver stiffness was measured by TE at BL and each year after OCA initiation at sites where FibroScan was the available form of TE. For PBO-pts in the DB phase, BL measures were the last assessment before the first OLE OCA dose. If pts received OCA in the DB phase, their BL measures were from the DB BL period. Data points after pts titrated to >10 mg OCA in the OLE were excluded from the analysis.
Results: OCA stabilized ELF over 24M in pts with evidence of moderate (ELF score ≥7.7 and < 9.8) or severe (≥9.8 and < 11.3) fibrosis or cirrhosis (≥11.3) at BL (Figure 1A). The mean ELF scores were 9 at BL, 9.19 at M12, and 9.31 at M24 in pts with moderate fibrosis. In pts with severe fibrosis, mean ELF scores were 10.35 at BL, 10.36 at M12, and 10.56 at M24, and for cirrhosis, mean ELF scores were 11.92 at BL, 11.54 at M12, and 11.35 at M24. In pts with lower liver stiffness (TE< 10 kPa) at BL, the mean TE measures were 6.09 at BL, 6.37 at M12, and 5.86 at M24 (Figure 1B). The mean TE measures in pts with higher liver stiffness (TE≥10 kPa) were 19.27 at BL, 18.39 at M12, and 17.37 at M24. ELF and TE values after M24 were similar to those observed from BL to M24, although the number of pts with TE and ELF measurements decreased over time through M72.
Discussion: The data suggest that OCA stabilized fibrosis over time regardless of BL severity. The interpretability of the data is limited after 24M because of decreasing sample size over time. Pts with PBC may benefit from OCA treatment early before PBC progresses and fibrosis worsens.
Figure: Figure 1. Mean ELF score (A) and liver stiffness measurement (B) over time in patients treated with OCA in the POISE study and OLE. Abbreviations: ELF, enhanced liver fibrosis; kPa, kilopascal; OCA, obeticholic acid; OLE, open-label extension; TE, transient elastography.
Disclosures:
Robert Gish: Abbott – Advisor or Review Panel Member, Consultant. AbbVie – Advisor or Review Panel Member, Advisory Committee/Board Member, Consultant, Speaker’s contract for promotional talks. Altimmune – Advisor or Review Panel Member, Consultant. AngioCrine – Stock Options. Antios – Advisor or Review Panel Member, Consultant. Arrowhead – Advisor or Review Panel Member, Consultant. BMS – Speaker’s contract for promotional talks. CoCrystal – Minor stock shareholder (liver space noted only). CymaBay Therapeutics – Data safety monitoring board. Durect – Data safety monitoring board. Dynavax – Advisor or Review Panel Member, Advisory Committee/Board Member, Consultant. Eiger – Advisor or Review Panel Member, Consultant, Stock Options. Eisai – Advisor or Review Panel Member, Consultant, Speaker’s contract for promotional talks. Enyo – Advisor or Review Panel Member, Consultant. Fujifilm/Wako – Advisory consultant, diagnostic companies. Genentech – Advisor or Review Panel Member, Consultant, Speaker’s contract for promotional talks. Genlantis – Advisor or Review Panel Member, Advisory Committee/Board Member, Consultant, Stock Options. Gerson Lehrman Group – Advisor or Review Panel Member, Consultant. Gilead Sciences – Advisor or Review Panel Member, Advisory Committee/Board Member, Consultant, Grant/Research Support, Speaker’s contract for promotional talks. Helios – Advisor or Review Panel Member, Advisory Committee/Board Member, Consultant. HepaTx – Advisor or Review Panel Member, Advisory Committee/Board Member, Consultant, Stock Options. HepQuant – Advisor or Review Panel Member, Advisory Committee/Board Member, Consultant, Stock Options. Intercept Pharmaceuticals Inc. – Advisor or Review Panel Member, Advisory Committee/Board Member, Consultant, Speaker’s contract for promotional talks. Janssen – Advisor or Review Panel Member, Advisory Committee/Board Member, Consultant. Merck – Advisor or Review Panel Member, Consultant. Perspectum – Advisory consultant, diagnostic companies. Pfizer – Advisor or Review Panel Member, Advisory Committee/Board Member, Consultant. Prodigy – Advisory Committee/Board Member, Chair of clinical advisory board. Quest – Advisory consultant, diagnostic companies:. RiboSciences – Minor stock shareholder (liver space noted only). Sonic Incytes – Advisory consultant, diagnostic companies:. Takeda – Data safety monitoring board. Topography Health – Advisor or Review Panel Member, Consultant, Current clinical trials alliance. Venatorx – Advisor or Review Panel Member, Consultant.
Darren Wheeler: Intercept Pharmaceuticals, Inc. – Employee.
Jing Li: Intercept Pharmaceuticals Inc. – Employee.
Christopher Gasink: Intercept Pharmaceuticals, Inc. – Employee. Johnson & Johnson – Employee.
Robert G. Gish, MD1, Darren Wheeler , PhD2, Jing Li, PhD2, Christopher Gasink, MD2, Alan Bonder, 3. P3492 - Stabilization of Enhanced Liver Fibrosis and Liver Stiffness Measures in the Open-Label Extension of the Phase 3 POISE Trial of Obeticholic Acid for the Treatment of Primary Biliary Cholangitis, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.
