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* = Presenting author

P235. Long-term clinical experience with vedolizumab (VDZ) in patients with mild to moderate ulcerative colitis (UC)

A. Parikh1, T. Leach1, J. Xu1, B. Feagan2

1Millennium Pharmaceuticals, Inc./Takeda Pharmaceuticals, Cambridge, United States; 2Robarts Research Insitute, London, Canada

Background: Binding of mucosal addressin cell adhesion molecule‑1 (MAdCAM‑1) by α4β7 mediates migration of leukocytes into gastrointestinal mucosa and associated lymphoid tissue. VDZ (previous versions MLN0002, MLN02, LDP-02) is an investigational gut-selective biologic that antagonizes α4β7. We describe the long-term clinical experience with VDZ in 53 patients with mild to moderate (UC) treated for up to 2.5 years.

Methods: UC patients were randomized to receive VDZ (2, 6, or 10 mg/kg) or placebo on days 1, 15, 29, and 85 in a dose-ranging study (DRS), after which (day 253) they received VDZ 2 or 6 mg/kg q8 weeks in an open-label, long-term extension study (ES) for up to an additional 547 days. Partial Mayo score (PMS) was used to assess efficacy. Safety, pharmacokinetics, pharmacodynamics, and immunogenicity were also assessed. At ES completion, subjects could continue to receive VDZ in an ongoing, phase 3 safety extension trial (experience not included).

Results: 38 patients received VDZ during the DRS and all continued in the ES. An additional 15 treatment-naïve patients were enrolled in the ES. 43 patients (81%) completed the ES. Reasons for discontinuation were lack of efficacy (n = 5), adverse event (AE) (n = 3) and withdrawal of consent (n = 2). Mean (SD) exposure to VDZ was 580.3 (167.2) days. Pretreatment mean (SD) PMS was 4.1 (1.9); at week 110, mean (SD) PMS was 0.7 (1.1). Remission rates ranged from 70% to 80% during the study. 70% of patients reported ≥1 AE; 11% reported ≥1 serious AE. The most common AEs were headache (19%), nasopharyngitis (17%), cough (9%), UC (8%) and URI (8%). One patient required hospitalization for a self-limited viral gastroenteritis, but no other significant infections were reported. One serious infusion reaction occurred in a patient with previous exposure to VDZ. 3 patients (6%) developed human anti-human antibody to VDZ. There were no cases of progressive multifocal leukoencephalopathy or deaths. Trough VDZ concentrations were dose proportional and remained steady and detectable throughout the study with nearly full inhibition of α4β7 receptors. 29 patients (55%) elected to continue to receive VDZ in the phase 3 ES.

Conclusions: Long-term VDZ administration was well tolerated, with a high rate of study completion. 2.0 mg/kg q 8 wks achieved target receptor saturation and was associated with durable mean decreases in disease activity.