Pharmacokinetics, Pharmacodynamics (PK/PD), and Safety Profile of Ulviprubart: Results from a 48-week, Open-label, Phase 1 Study in Patients with Inclusion Body Myositis (IBM)
Merrilee Needham1, Robert D. Henderson2, Christina Liang3, Dulce Soler-Ferran4, H. Jeffrey Wilkins4, Steven A. Greenberg5
1Perron Institute, QEII Medical Centre; University of Notre Dame; Fiona Stanley Hospital; Murdoch University, 2Department of Neurology, Royal Brisbane & Women's Hospital; University of Queensland Centre for Clinical Research, University of Queensland, 3Royal North Shore Hospital, Sydney Medical School, 4Abcuro, Inc., 5Abcuro, Inc.; Brigham and Women’s Hospital, Harvard Medical School
Objective:
To describe the PK/PD and safety profile of ulviprubart in patients with IBM.
Background:
IBM is a rare, progressive disease characterized by invasion of healthy muscle by highly differentiated cytotoxic CD8+ T cells and associated with loss of grip strength, difficulty walking, and/or dysphagia. There are no disease-modifying therapies currently available for patients with IBM. Ulviprubart is a monoclonal antibody that selectively depletes cytotoxic CD8+ KLRG1+ T cells by targeting the cell-surface marker KLRG1 expressed on the vast majority of IBM-muscle–infiltrating T cells. Ulviprubart may have clinical activity in patients with IBM.
Design/Methods:
In this phase 1, open-label study (NCT04659031), patients received subcutaneous ulviprubart (0.1, 0.5, or 2.0 mg/kg) as a single dose and approximately 6−12 months later were dosed once every 8 weeks (Q8W) or received initial multiple dosing of 2.0 mg/kg Q8W, for up to 48 weeks. PK/PD and safety assessments were performed at multiple timepoints.
Results:
Nineteen patients (mean age, 66 years; 79% male; mean disease duration, 10 years) were enrolled (0.1 mg/kg: n=3; 0.5 mg/kg: n=3; 2.0 mg/kg: n=13). Ulviprubart displayed a long absorption phase, slow clearance, and a half-life of 14−21 days. Depletion of peripheral CD8+ KLRG1+ and CD4+ KLRG1+ T cells was evident on day 1 postdose, with mean CD8+ KLRG1+ T cell maximum depletions of 69%, 97%, and 98% achieved by weeks 2–3 after a single dose of 0.1, 0.5, and 2.0 mg/kg, respectively. Depletion was sustained through the study. Protective regulatory T cells and B cells were preserved. No serious adverse events (AEs) or discontinuations due to AEs were reported.
Conclusions:
Ulviprubart led to deep and selective depletion of peripheral blood KLRG1+ T cells in patients with IBM. Together with the favorable safety profile, these data support the continued development of ulviprubart.
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