PILOT STUDY OF VOLIXIBAT CO-ADMINISTERED WITH OCA FOR PRIMARY BILIARY CHOLANGITIS (PBC) TREATMENT: THE VLX-602 TRIAL

Document Type

Conference Proceeding

Publication Date

10-9-2024

Publication Title

Hepatology

Abstract

Background: PBC is a progressive inflammatory cholestatic disease with liver bile flow impairment and destruction of intrahepatic bile ducts. Bile acid (BA) levels are commonly elevated with disease severity and progression with cholestatic pruritus being a debilitating complication. Volixibat (VLX) is an ileal bile acid transporter (IBAT) inhibitor that interrupts BA uptake in the small intestine, leading to greater BA fecal elimination with subsequent reductions in the systemic BA pool. IBAT inhibitors have shown efficacy to treat cholestatic pruritus, including in PBC, but concurrent use of an IBAT inhibitor and obeticholic acid (OCA) is not well studied. VLX-602 is a pilot study to evaluate the safety of VLX (80 mg BID) in participants with PBC who were on active treatment with OCA (5 or 10 mg). Methods: VLX-602 was a multicenter, open-label study that enrolled patients with PBC with ongoing treatment with OCA for ≥ 3 months with a stable ALP level. The study consisted of screening (14 days), study treatment (OCA + VLX, 6 weeks), and follow-up (1 week) periods. Safety was assessed by TEAE collection and laboratory measurements, including liver chemistry. Other assessments included: 7aC4, sBA, PK and autotaxin levels, along with the itch PROs (PIS-Itch, WI-NRS, and PGICItch). Results: Six participants were enrolled, all female, with mean age of 56.5 years. The most common TRAE was diarrhea (83.3%). Other TRAEs that affected 1 participant each (16.7% each) were nausea, fatigue, and vomiting. Other TEAEs (not related to study drug) that affected 1 participant each (16.7% each) were toothache, nasopharyngitis, and upper respiratory tract infection. No severe, serious, or events that led to study discontinuation or death were reported. Mean levels of AST, ALT, total bilirubin, and ALP were stable between baseline and end of the treatment period. Overall, 3 participants showed improvement in their itch scores for both WI-NRS and PIS-Itch while on VLX. At the follow-up visit, after VLX was discontinued, 3 and 4 participants had worsening in their WI-NRS scores and PIS-Itch scores, respectively. Conclusion: These safety pilot study data were consistent with the known safety profile of IBAT inhibitors. The addition of VLX to OCA treatment in PBC led to improvement in itch in some patients, with reversal of the effect upon VLX cessation. The results of this study justify additional investigation of the safety and efficacy of VLX for the treatment of PBC, with or without a background regimen of OCA.

Volume

80

First Page

S1829

Last Page

S1830

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