TY - JOUR
T1 - Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis
T2 - APLIOS, a randomized phase-2 study
AU - Bar-Or, Amit
AU - Wiendl, Heinz
AU - Montalban, Xavier
AU - Alvarez, Enrique
AU - Davydovskaya, Maria
AU - Delgado, Silvia R.
AU - Evdoshenko, Evgeniy P.
AU - Giedraitiene, Natasa
AU - Gross-Paju, Katrin
AU - Haldre, Sulev
AU - Herrman, Craig E.
AU - Izquierdo, Guillermo
AU - Karelis, Guntis
AU - Leutmezer, Fritz
AU - Mares, Miroslav
AU - Meca-Lallana, Jose E.
AU - Mickeviciene, Dalia
AU - Nicholas, Jacqueline
AU - Robertson, Derrick S.
AU - Sazonov, Denis V.
AU - Sharlin, Kenneth
AU - Sundaram, Bharathy
AU - Totolyan, Natalia
AU - Vachova, Marta
AU - Valis, Martin
AU - Bagger, Morten
AU - Häring, Dieter A.
AU - Ludwig, Inga
AU - Willi, Roman
AU - Zalesak, Martin
AU - Su, Wendy
AU - Merschhemke, Martin
AU - Fox, Edward J.
N1 - Publisher Copyright:
© The Author(s), 2021.
PY - 2022/5
Y1 - 2022/5
N2 - 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 (AUCτ) 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 AUCτ, 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.
AB - 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 (AUCτ) 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 AUCτ, 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.
KW - autoinjector pen
KW - bioequivalence
KW - multiple sclerosis
KW - Ofatumumab
KW - pharmacokinetics
KW - pre-filled syringe
UR - http://www.scopus.com/inward/record.url?scp=85116372494&partnerID=8YFLogxK
U2 - 10.1177/13524585211044479
DO - 10.1177/13524585211044479
M3 - Article
C2 - 34605319
AN - SCOPUS:85116372494
SN - 1352-4585
VL - 28
SP - 910
EP - 924
JO - Multiple Sclerosis Journal
JF - Multiple Sclerosis Journal
IS - 6
ER -