Slide 1: Efficacy and Safety of Volixibat in PSC and Pruritus: Results of the VISTAS Trial
Efficacy and Safety of Volixibat, an IBAT Inhibitor, in Patients With Primary Sclerosing Cholangitis and Moderate-to-Severe Pruritus: Results of the VISTAS Trial Cynthia Levy,1 on behalf of the VISTAS study group 1 Schiff Center for Liver Diseases, University of Miami Miller School of Medicine, Miam
Slide 2: Primary Sclerosing Cholangitis (PSC)
Primary Sclerosing Cholangitis (PSC)1-7 Progressive Biliary Injury Drives Serious and Compounding Cholestasis and Liver Damage Disease Consequences Significant Unmet Need Pruritus and Fatigue Heavy symptom burden No Approved Therapies for Elevated Laboratory Tests Disease and Symptoms ALP, Bilirubin
Slide 3: IBAT Inhibitors May Reduce Clinical Effects of Chronic Cholestasis
IBAT Inhibitors May Reduce Clinical Effects of Chronic Cholestasis Clinical effects of IBAT inhibitors Redirects bile acid flow by seen in cholestatic diseases1-3 inhibiting reuptake by IBAT IBATi clinical studies show: Impact on bile acid pharmacodynamic markers: Interrupts recirculation of chole
Slide 4: VISTAS: Largest Global Clinical Trial With IBAT Inhibitors in PSC With 103 Study Sites
VISTAS: Largest Global Clinical Trial With IBAT Inhibitors in PSC With 103 Study Sites IBAT, ileal bile acid transporter; PSC, primary sclerosing cholangitis. 4
Slide 5: VISTAS Study Design: Primary Cohort
VISTAS Study Design: Primary Cohort Key Entry Criteria • Confirmed VLX 20 mg BID (n=54) VLX R diagnosis of PSC 1:1 Open-label per AASLD Placebo BID (n=57) Extension guidelines Study • Aged ≥12 years at Baseline Week 28 Baseline • Moderate to severe pruritus Primary Endpoint Select Secondary Endpoint
Slide 6: Adult Itch-Reported Outcome (ItchRO) Scale: Description
Adult Itch-Reported Outcome (ItchRO) Scale: Description • The Adult ItchRO is a single-item daily diary that Adult ItchRO assesses the severity of itching over the past 24 hours with use of a worst itch numeric rating scale (WI-NRS) • Originally developed, tested, and content validity confirmed in p
Slide 7: VISTAS Primary Cohort: Key Demographic Characteristics
VISTAS Primary Cohort: Key Demographic Characteristics VLX 20 mg BID Placebo BID Parametera (n=54) (n=57) Age at enrollment, yearsb 45.2 (15.7) 44.3 (14.2) Time since PSC diagnosis in years 8.4 (7.2) 9.7 (8.3) Male 29 (53.7) 22 (38.6) PSC Type Large Duct 49 (90.7) 53 (93.0) IBD 40 (74.1) 42 (73.7) U
Slide 8: VISTAS Primary Cohort: Additional Key Baseline Characteristics
VISTAS Primary Cohort: Additional Key Baseline Characteristics VLX 20 mg BID Placebo BID Parametera (n=54) (n=57) ItchRO Scoreb 6.3 (1.6) 6.1 (1.5) sBA, µmol/L 109.6 (137.5) 61.4 (83.2) ALT, U/L 73 (46.8) 87 (58.5) AST, U/L 61 (30.2) 72 (46.7) Total Bilirubin, µmol/L 20.1 (13.9) 18.5 (14.2) Direct B
Slide 9: Participants Who Received Volixibat Showed Statistically Significant Reductions in Cholestatic Pruritus
VISTAS Primary Cohort Results: Participants Who Received Volixibat Showed Statistically Significant Reductions in Cholestatic Pruritus Pruritus Score (Adult ItchRO) MMRM Analysisa VLX 20 mg BID Placebo BID (n=54) (n=57) 0 LS Mean CFB in Adult ItchROb Mean (SD) Adult ItchRO -1.08 Scores at Baseline:
Slide 10: Participants Who Received Volixibat Showed Reductions in Cholestatic Pruritus Over Time
VISTAS Primary Cohort Results: Participants Who Received Volixibat Showed Reductions in Cholestatic Pruritus Over Time Average Pruritus Score (Adult ItchRO) 0 CFB in Adult ItchROa,b -1 Improvement -2 -3 VLX 20 mg BID Placebo BID -4 BL 28 Week Rapid and sustained reductions in pruritus were observed
Slide 11: Pruritus Responder Analysis Across Participants
VISTAS Primary Cohort Results: Pruritus Responder Analysis Across Participants Proportion of Pruritus Responders 80% VLX 20mg BID Placebo BID Responder Thresholds: P=0.0019 • ≥2-point reduction from 60% Baseline defined as Responders, % 56% meaningful improvement for P=0.0011 patients 40% 37% 20% 26
Slide 12: Participants Who Received Volixibat Showed Improvements in Fatigue and Sleep
VISTAS Primary Cohort Results: Participants Who Received Volixibat Showed Improvements in Fatigue and Sleep Change in PROMIS Scores at Week 28 Fatigue Sleep Disturbance LS Mean CFBa in PROMIS domain scores 1 0 -0.78 -1 -1.89 -2 VLX 20 mg BID Improvement Placebo BID -3 -4 -4.22 -5 -6 -2.33 (P=0.1322)
Slide 13: Participants Who Received Volixibat Showed Statistically Significant Reductions in sBA Levels
VISTAS Primary Cohort Results: Participants Who Received Volixibat Showed Statistically Significant Reductions in sBA Levels sBA Levels MMRM Analysisa VLX 20 mg BID Placebo BID (n=54) (n=57) 40 LS Mean CFB in sBA, µmol/L 2.1 20 Improvement 0 -20 -33.7 -40 -35.8 (P=0.0324) -60 Statistically significa
Slide 14: Median Change from Baseline in Alkaline Phosphatase and Total Bilirubin: Primary Cohort
Median Change from Baseline in Alkaline Phosphatase and Total Bilirubin: Primary Cohort 7.5 90 6.0 60 4.5 CFB in Total Bilirubina 30 3.0 CFB in ALPa 1.5 0 0 -30 -1.5 -60 -3.0 -90 VLX 20 mg BID Placebo BID -4.5 VLX 20 mg BID Placebo BID BL 28 BL 28 Week Week aData are median (Q1, Q3) changes from bas
Slide 15: Safety Analysis in Primary and Secondary Cohorts: Summary of TEAEs
VISTAS Safety Analysis in Primary and Secondary Cohorts: Summary of TEAEs VLX 20 mg BID Placebo BID Parameter (N=77) (N=81) No. (%) of Participants with Any TEAE 72 (93.5) 68 (84.0) Related TEAEs 34 (44.2) 16 (19.8) Grade 3 or higher TEAEs 10 (13.0) 9 (11.1) Related Grade 3 or higher TEAEs 2 (2.6) 3
Slide 16: Safety Analysis: Participants With Any TEAE ≥5%
VISTAS Safety Analysis in Primary and Secondary Cohorts: Participants With Any TEAE ≥5% VLX 20 mg BID Placebo BID Preferred Term (N=77) (N=81) No. (%) of Participants with Any TEAE 72 (93.5) 68 (84.0) Diarrhoea 31 (40.3) 7 (8.6) Abdominal Pain 14 (18.2) 8 (9.9) Nausea 10 (13.0) 3 (3.7) Vitamin D def
Slide 17: Conclusions
Conclusions VISTAS is the largest interventional study investigating the efficacy and safety of an IBAT inhibitor in PSC and is the first controlled evidence of a potential therapy addressing the cholestatic symptom burden in patients with PSC. Volixibat led to rapid, significant, and sustained impr
Slide 18: Acknowledgements
Acknowledgements The authors would like to thank the study participants, their families, and the investigators for their participation in this study 18
Slide 19: VISTAS Investigators and Authors
VISTAS Investigators and Authors Affiliation Authors Affiliation Authors Schiff Center for Liver Diseases, University of Miami Miller School of Université Grenoble Alpes, Service hépatogastroenterologie, CHU Grenoble Cynthia Levy Marie-Noëlle Hilleret Medicine, Miami, FL, USA Alpes, Grenoble, France
Slide 20: VISTAS Investigators and Authors
VISTAS Investigators and Authors Affiliation Authors Affiliation Authors Hadassah Medical Organization, The Liver Institute, Jerusalem, Israel Rifaat Safadi University of Milano-Bicocca, ASST GOM Niguarda, Milan, Italy Marco Carbone Northern Health, Melbourne, Australia Siddharth Sood Cliniques Univ