TY - JOUR
T1 - Interim results from an ongoing, open-label, single-arm trial of odevixibat in progressive familial intrahepatic cholestasis
AU - Thompson, Richard J.
AU - Artan, Reha
AU - Baumann, Ulrich
AU - Calvo, Pier Luigi
AU - Czubkowski, Piotr
AU - Dalgic, Buket
AU - D'Antiga, Lorenzo
AU - Di Giorgio, Angelo
AU - Durmaz, Özlem
AU - Gonzalès, Emmanuel
AU - Grammatikopoulos, Tassos
AU - Gupte, Girish
AU - Hardikar, Winita
AU - Houwen, Roderick H.J.
AU - Kamath, Binita M.
AU - Karpen, Saul J.
AU - Lacaille, Florence
AU - Lachaux, Alain
AU - Lainka, Elke
AU - Loomes, Kathleen M.
AU - Mack, Cara L.
AU - Mattsson, Jan P.
AU - McKiernan, Patrick
AU - Ni, Quanhong
AU - Özen, Hasan
AU - Rajwal, Sanjay R.
AU - Roquelaure, Bertrand
AU - Shteyer, Eyal
AU - Sokal, Etienne
AU - Sokol, Ronald J.
AU - Soufi, Nisreen
AU - Sturm, Ekkehard
AU - Tessier, Mary Elizabeth
AU - van der Woerd, Wendy L.
AU - Verkade, Henkjan J.
AU - Vittorio, Jennifer M.
AU - Wallefors, Terese
AU - Warholic, Natalie
AU - Yu, Qifeng
AU - Horn, Patrick
AU - Kjems, Lise
N1 - Funding Information:
Editorial and medical writing support was provided by Peloton Advantage, LLC, an OPEN Health company, and was funded by Albireo Pharma, Inc.
Publisher Copyright:
© 2023 The Authors
PY - 2023/8
Y1 - 2023/8
N2 - Background & Aims: PEDFIC 2, an ongoing, open-label, 72-week study, evaluates odevixibat, an ileal bile acid transporter inhibitor, in patients with progressive familial intrahepatic cholestasis. Methods: PEDFIC 2 enrolled and dosed 69 patients across two cohorts; all received odevixibat 120 μg/kg per day. Cohort 1 comprised children from PEDFIC 1, and cohort 2 comprised new patients (any age). We report data through 15 July 2020, with Week 24 of PEDFIC 2 the main time point analysed. This represents up to 48 weeks of cumulative exposure for patients treated with odevixibat from the 24-week PEDFIC 1 study (cohort 1A) and up to 24 weeks of treatment for those who initiated odevixibat in PEDFIC 2 (patients who received placebo in PEDFIC 1 [cohort 1B] or cohort 2 patients). Primary endpoints for this prespecified interim analysis were change from baseline to Weeks 22–24 in serum bile acids (sBAs) and proportion of positive pruritus assessments (≥1-point drop from PEDFIC 2 baseline in pruritus on a 0–4 scale or score ≤1) over the 24-week period. Safety monitoring included evaluating treatment-emergent adverse events (TEAEs). Results: In cohort 1A, mean change from PEDFIC 1 baseline to Weeks 22–24 of PEDFIC 2 in sBAs was -201 μmol/L (p <0.0001). For cohort 1B and cohort 2, mean changes from odevixibat initiation to weeks 22–24 in sBAs were -144 and -104 μmol/L, respectively. The proportion of positive pruritus assessments in the first 24-week period of PEDFIC 2 was 33%, 56%, and 62% in cohorts 1A, 1B, and 2, respectively. Most TEAEs were mild or moderate. No drug-related serious TEAEs occurred. Conclusions: Odevixibat in patients with progressive familial intrahepatic cholestasis was generally well tolerated and associated with sustained reductions in sBAs and pruritus. Clinical Trials Registration: This study is registered at ClinicalTrials.gov (NCT03659916). Impact and Implications: Disrupted bile flow is a hallmark feature of patients with progressive familial intrahepatic cholestasis and can result in build-up of bile constituents in the liver with spill over into the bloodstream; other effects that patients can experience include extremely itchy skin, and because not enough bile reaches the gut, patients can have problems digesting food, which may lead to poor growth. Odevixibat is an orally administered medication that shunts bile acids away from the liver. The current study, called PEDFIC 2, suggested that odevixibat can improve the problematic signs and symptoms of progressive familial intrahepatic cholestasis and was generally safe for patients.
AB - Background & Aims: PEDFIC 2, an ongoing, open-label, 72-week study, evaluates odevixibat, an ileal bile acid transporter inhibitor, in patients with progressive familial intrahepatic cholestasis. Methods: PEDFIC 2 enrolled and dosed 69 patients across two cohorts; all received odevixibat 120 μg/kg per day. Cohort 1 comprised children from PEDFIC 1, and cohort 2 comprised new patients (any age). We report data through 15 July 2020, with Week 24 of PEDFIC 2 the main time point analysed. This represents up to 48 weeks of cumulative exposure for patients treated with odevixibat from the 24-week PEDFIC 1 study (cohort 1A) and up to 24 weeks of treatment for those who initiated odevixibat in PEDFIC 2 (patients who received placebo in PEDFIC 1 [cohort 1B] or cohort 2 patients). Primary endpoints for this prespecified interim analysis were change from baseline to Weeks 22–24 in serum bile acids (sBAs) and proportion of positive pruritus assessments (≥1-point drop from PEDFIC 2 baseline in pruritus on a 0–4 scale or score ≤1) over the 24-week period. Safety monitoring included evaluating treatment-emergent adverse events (TEAEs). Results: In cohort 1A, mean change from PEDFIC 1 baseline to Weeks 22–24 of PEDFIC 2 in sBAs was -201 μmol/L (p <0.0001). For cohort 1B and cohort 2, mean changes from odevixibat initiation to weeks 22–24 in sBAs were -144 and -104 μmol/L, respectively. The proportion of positive pruritus assessments in the first 24-week period of PEDFIC 2 was 33%, 56%, and 62% in cohorts 1A, 1B, and 2, respectively. Most TEAEs were mild or moderate. No drug-related serious TEAEs occurred. Conclusions: Odevixibat in patients with progressive familial intrahepatic cholestasis was generally well tolerated and associated with sustained reductions in sBAs and pruritus. Clinical Trials Registration: This study is registered at ClinicalTrials.gov (NCT03659916). Impact and Implications: Disrupted bile flow is a hallmark feature of patients with progressive familial intrahepatic cholestasis and can result in build-up of bile constituents in the liver with spill over into the bloodstream; other effects that patients can experience include extremely itchy skin, and because not enough bile reaches the gut, patients can have problems digesting food, which may lead to poor growth. Odevixibat is an orally administered medication that shunts bile acids away from the liver. The current study, called PEDFIC 2, suggested that odevixibat can improve the problematic signs and symptoms of progressive familial intrahepatic cholestasis and was generally safe for patients.
KW - Bile acids and salts
KW - Clinical trial
KW - Enterohepatic circulation
KW - Liver diseases
UR - http://www.scopus.com/inward/record.url?scp=85164128981&partnerID=8YFLogxK
U2 - 10.1016/j.jhepr.2023.100782
DO - 10.1016/j.jhepr.2023.100782
M3 - Article
C2 - 37456676
AN - SCOPUS:85164128981
SN - 2589-5559
VL - 5
JO - JHEP Reports
JF - JHEP Reports
IS - 8
M1 - 100782
ER -