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
AU - APLIOS Trial Investigators
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 - Ofatumumab
KW - autoinjector pen
KW - bioequivalence
KW - multiple sclerosis
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
SN - 1352-4585
VL - 28
SP - 910
EP - 924
JO - Multiple Sclerosis Journal
JF - Multiple Sclerosis Journal
IS - 6
ER -