Slide 1: Volixibat for the Treatment of Cholestatic Pruritus in PBC: VANTAGE 28-Week Interim Results
Volixibat for the Treatment of Cholestatic Pruritus in Primary Biliary Cholangitis: An Adaptive, Randomized, Placebo- Controlled Phase 2b Trial (VANTAGE): 28-Week Interim Results Michael A. Heneghan,1 Mitchell L. Shiffman,2 Debra Weinstein,3 Victor Ankoma-Sey,4 Nimer Assy,5 Dian-Jung Chiang,6 Mauriz
Slide 2: Primary Biliary Cholangitis (PBC)
Primary Biliary Cholangitis (PBC) • Chronic, progressive, immune-mediated condition leading to destruction of small intrahepatic bile ducts1,2 • Estimated prevalence 1.9 to 40.2 per 100,000 persons. Women are predominantly affected,1 with a sex ratio of 9:1 • Key clinical features and complications
Slide 3: IBAT Inhibitors May Reduce Clinical Effects of Cholestasis in Patients With PBC
IBAT Inhibitors May Reduce Clinical Effects of Cholestasis in Patients With PBC Clinical effects of IBAT inhibitors Redirects bile acid flow by seen in cholestasis1-3 inhibiting reuptake by IBAT IBATi clinical studies show: Reductions in pruritus Interrupts recirculation of bile acids to the liver
Slide 4: VANTAGE Phase 2 Study Design
VANTAGE Phase 2 Study Design VLX 20 mg BID (n=10) Completed Part 1: R Key Entry Criteria 1:1:1 VLX 80 mg BID (n=10) • Confirmed diagnosis Dose selection of PBC per AASLD Placebo BID (n=11) VLX guidelines Open-label • Aged ≥18 years at Extension Baseline Enrolling VLX 20 mg BID Study Part 2: R • Mode
Slide 5: Key Demographics and Baseline Characteristics
Key Demographics and Baseline Characteristics VLX 20 mg BID VLX 80 mg BID Placebo BID Total Parametera (n=10) (n=10) (n=11) (N=31) Age, years 53.9 (15.8) 52.3 (5.9) 62.1 (9.7) 56.3 (11.7) Sex, female 8 (80) 9 (90) 10 (91) 27 (87) Pruritus, Adult ItchRO scoreb 6.8 (1.6) 6.3 (1.8) 6.2 (1.5) 6.4 (1.6)
Slide 6: Participants Who Received Volixibat Showed Statistically Significant Reductions in Pruritus
Participants Who Received Volixibat Showed Statistically Significant Reductions in Pruritus Pruritus Score (Adult ItchRO) MMRM Analysisa VLX 20 mg BID VLX 80 mg BID Placebo BID (n=10) (n=10) (n=11) 0 Mean CFB in Adult ItchRO -1 -1.3 -2 Improvement * -3 -3.7 -3.9 -4 -5 ** ** -6 -2.6 (P=0.0010) -2.4 (
Slide 7: Participants Who Received Volixibat Showed Reductions in Pruritus Over Time
Participants Who Received Volixibat Showed Reductions in Pruritus Over Time Average Pruritus Score (Adult ItchRO) Over 28 Weeks 1 0 CFB in Adult ItchROa -1 Improvement -2 -3 -4 -5 -6 VLX 20 mg BID (n=10) VLX 80 mg BID (n=10) Placebo (n=11) BL 28 Week Rapid reductions in pruritus were observed after
Slide 8: A Majority of Participants Who Received Volixibat Showed an sBA Response
A Majority of Participants Who Received Volixibat Showed an sBA Response sBA Respondersa,b ≥50% reduction from Baseline 100 P=0.095 80 80 P=0.30 Responders, % 60 60 40 36 20 0 VLX 20 mg BID VLX 80 mg BID Placebo BID (n=10) (n=10) (n=11) A higher proportion of participants who received volixibat show
Slide 9: Interleukin-31 and Pro-C3 Levels After Volixibat Treatment
Interleukin-31 and Pro-C3 Levels After Volixibat Treatment Interleukin-31 Levels Over Time Pro-C3 Levels Over Time 25 60 20 Interleukin-31, ng/La Pro-C3 level, µg/La 15 50 10 40 5 0 BL 28 BL 28 Week Week VLX 20 mg BID (n=10) VLX 80 mg BID (n=10) VLX 20 mg BID (n=8) VLX 80 mg BID (n=10) Placebo BID (
Slide 10: Participants Who Received Volixibat Showed Improvements in HRQoL
Participants Who Received Volixibat Showed Improvements in HRQoL Change in PROMIS Scores Change in PBC-40 Scores Fatigue Sleep Fatigue 0 0 -0.5 -0.5 -1.0 -1.0 CFB in PBC-40 domain scoresa CFB in PROMIS domain scoresa -1 -1 -1.5 -1.5 Improvement -2 -2 -2.5 -2.4 -2.5 -3 -3 -3.5 -3.8 -4 -4.3 -3.5 -4.5
Slide 11: Summary of TEAEs
Summary of TEAEs VLX 20 mg VLX 80 mg Placebo Total TEAE, n (%)a (n=11) (n=11) (n=16) (N=38) Any TEAE 11 (100.0) 11 (100.0) 12 (75.0) 34 (89.5) TEAEs grade ≥3 2 (18.2) 2 (18.2) 1 (6.3) 5 (13.2) TEAEs related to study drug 9 (81.8) 8 (72.7) 3 (18.8) 20 (52.6) TEAEs related to study drug grade ≥3 1 (9.
Slide 12: Additional Safety Details
Additional Safety Details • Diarrhoea was the most common TEAE, reported in up to 77% (17 of 22) of all participants receiving volixibat – Diarrhoea was mild to moderate in severity and led to 1 discontinuation • Serious TEAEs were unrelated to study drug, including: – Syncope and suicide attempt (V
Slide 13: Conclusions
Conclusions • Rapid and statistically significant reductions in cholestatic pruritus were observed after treatment with volixibat – Change from Baseline in Adult ItchRO was similar between the volixibat 20 mg and volixibat 80 mg cohorts • Numerically greater reductions in sBA levels were observed wi
Slide 14: Acknowledgements
Acknowledgements • The authors would like to thank the study participants, their families and the investigators for their participation in this study. 14
Slide 15: Investigators and Authors
Investigators and Authors Affiliation Authors Affiliation Authors Michael A. Heneghan, Yooyun UF Hepatology Research at CTRB, Gainesville, King’s College Hospital, London, United Kingdom Roberto Firpi-Morell Chung, Ilkay Ergenc Florida, USA Liver Institute of Virginia, Bon Secours Mercy Health, Klin
Slide 16: Disclosures
Disclosures • MAH reports consulting fees from Mirum and Ipsen, royalties from Up To Date, and speaker fees from Advanz Pharmaceuticals, Falk, and Ipsen. • KVK reports personal fees from AbbVie, Gilead, Intercept and Ipsen; receives grants from 89bio, Boston, CymaBay, Gilead, GSK, Hanmi, HighTide, I
Slide 17: Thank you!
Thank you! 17