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.

A Bar Or Center for Neuroinflammation and Experimental Therapeutics and Department of Neurology Perelman School of Medicine University of Pennsylvania 3400 Spruce Street 3 Gates Building Philadelphia PA 19104 USA

Center for Neuroinflammation and Experimental Therapeutics and Department of Neurology Perelman School of Medicine University of Pennsylvania Philadelphia PA USA

Central Texas Neurology Consultants PA Round Rock TX USA

Centre d'Esclerosi Múltiple de Catalunya Hospital Universitari Vall d'Hebron Barcelona Spain

Clinic of Neurology and Neurosurgery Institute of Clinical Medicine Faculty of Medicine Vilnius University Vilnius Lithuania

Department of Clinical Trials FSBIH SDMC of FMBA of Russia Novosibirsk Russian Federation

Department of Neurology 1st Pavlov State Medical University of St Petersburg St Petersburg Russian Federation

Department of Neurology and Neurosurgery University of Tartu Tartu Estonia Neurology Clinic Tartu University Hospital Tartu Estonia

Department of Neurology Faculty of Medicine in Hradec Králové Charles University Prague and University Hospital Hradec Králové Hradec Králové Czech Republic

Department of Neurology Medical University of Vienna Vienna Austria

Department of Neurology Pardubice Regional Hospital Pardubice Czech Republic

Department of Neurology Rocky Mountain MS Center University of Colorado Aurora CO USA

Department of Neurology Teplice Hospital Teplice Czech Republic

Department of Neurology with Institute of Translational Neurology University of Münster Münster Germany

JWM Neurology Indianapolis IN USA

Lithuanian University of Health Sciences Kaunas Lithuania

MS Center and Department of Neurology Miller School of Medicine University of Miami Miami FL USA

Multiple Sclerosis CSUR Department of Neurology Virgen de la Arrixaca Clinical University Hospital IMIB Arrixaca Murcia Spain Clinical Neuroimmunology and Multiple Sclerosis Cathedra Universidad Católica San Antonio Murcia Spain

Multiple Sclerosis Division Department of Neurology Morsani College of Medicine University of South Florida Tampa FL USA

Multiple Sclerosis Unit Hospital Vithas NISA Sevilla Sevilla Spain

Neurology and Neurosurgery Department Riga East University Hospital and Riga Stradins University Riga Latvia

Novartis Pharma AG Basel Switzerland

Novartis Pharmaceutical Corporation East Hanover NJ USA

OhioHealth Riverside Methodist Hospital Columbus OH USA

Pirogov Russian National Research Medical University Moscow Russian Federation

Sharlin Health and Neurology Ozark MO USA

St Petersburg Center for Multiple Sclerosis and Other Autoimmune Diseases St Petersburg Russian Federation

Texas Institute for Neurological Disorders Sherman TX USA

West Tallinn Central Hospital Tallinn Estonia Institute of Health Care Technology TalTech Tallinn Estonia

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NCT03560739