| Authors |
Bar-Or, Amit ; Wiendl, Heinz ; Montalban, Xavier ; Alvarez, Enrique ; Davydovskaya, Maria ; Delgado, Silvia R ; Evdoshenko, Evgeniy P ; Giedraitienė, Nataša ; Gross-Paju, Katrin ; Haldre, Sulev ; Herrman, Craig E ; Izquierdo, Guillermo ; Karelis, Guntis ; Leutmezer, Fritz ; Mares, Miroslav ; Meca-Lallana, Jose E ; Mickevičienė, Dalia ; Nicholas, Jacqueline ; Robertson, Derrick S ; Sazonov, Denis V ; Sharlin, Kenneth ; Sundaram, Bharathy ; Totolyan, Natalia ; Vachova, Marta ; Valis, Martin ; Bagger, Morten ; Häring, Dieter A ; Ludwig, Inga ; Willi, Roman ; Zalesak, Martin ; Su, Wendy ; Merschhemke, Martin ; Fox, Edward J |
| Abstract [eng] |
Background: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, is approved in several countries for relapsing multiple sclerosis (RMS). Objective: To demonstrate the bioequivalence of ofatumumab administered by an autoinjector versus a pre-filled syringe (PFS) and to explore the effect of ofatumumab on B-cell depletion. Methods: APLIOS (NCT03560739) is a 12-week, open-label, parallel-group, phase-2 study in patients with RMS receiving subcutaneous ofatumumab 20 mg every 4 weeks (q4w) (from Week 4, after initial doses on Days 1, 7, and 14). Patients were randomized 10:10:1:1 to autoinjector or PFS in the abdomen, or autoinjector or PFS in the thigh, respectively. Bioequivalence was determined by area under the curve (AUC τ) and maximum plasma concentration (Cmax) for Weeks 8–12. B-cell depletion and safety/tolerability were assessed. Results: A total of 256 patients contributed to the bioequivalence analyses (autoinjector-abdomen, n = 128; PFS-abdomen, n = 128). Abdominal ofatumumab pharmacokinetic exposure was bioequivalent for autoinjector and PFS (geometric mean AUC τ, 487.7 vs 474.1 h × µg/mL (ratio 1.03); Cmax, 1.409 vs 1.409 µg/mL (ratio 1.00)). B-cell counts (median cells/µL) depleted rapidly in all groups from 214.0 (baseline) to 2.0 (Day 14). Ofatumumab was well tolerated. Conclusion: Ofatumumab 20 mg q4w self-administered subcutaneously via autoinjector is bioequivalent to PFS administration and provides rapid B-cell depletion. |
