ofatumumab — Drug Monograph

Brand names: Arzerra

Drug class: Monoclonal Antibody

Mechanism of Action

Fully human anti-CD20 IgG1 monoclonal antibody that binds a unique membrane-proximal small-loop epitope on CD20, distinct from the rituximab-binding site. This epitope is closer to the cell membrane and dissociates more slowly from CD20, resulting in prolonged binding and potent complement-dependent cytotoxicity (CDC). Also induces ADCC and ADCP. The membrane-proximal binding location may allow activity in cells with lower CD20 expression density.

FDA Indications

• Refractory chronic lymphocytic leukemia (CLL) in patients for whom fludarabine and alemtuzumab therapy are inappropriate (FDA approval October 2009, CLL-F-202/IHUMF study)
• NOTE: Ofatumumab (Arzerra) for CLL/oncology indications was voluntarily withdrawn from the US market in 2019 by Novartis/Genmab for commercial reasons (not safety or efficacy). It is no longer marketed in the US for oncologic indications.
• NOTE: Ofatumumab is separately marketed under the brand name Kesimpta (subcutaneous formulation) for relapsing forms of multiple sclerosis — this is a distinct indication and product, not an oncology use.

Common Side Effects

• Infusion-related reactions (first and second infusions particularly)
• Neutropenia
• Pneumonia
• Pyrexia
• Cough
• Diarrhea
• Fatigue
• Anemia

Clinical Pearl

Ofatumumab (Arzerra) was the first fully human anti-CD20 antibody approved for CLL and was notable for its potent CDC compared to rituximab, attributed to its unique membrane-proximal CD20 epitope. However, Arzerra was voluntarily withdrawn from the US market in 2019 by Novartis/Genmab for commercial (not safety) reasons, as it faced strong competition. Ofatumumab lives on in the MS space as Kesimpta (SC formulation, 20 mg monthly), which is an entirely separate product and indication from the…

Related Therapies & Mechanisms

• Alemtuzumab (Campath) — Monoclonal Antibody · Leukemia
• Obinutuzumab (Gazyva) — Monoclonal Antibody · Lymphoma
• Rituximab (Rituxan) — Monoclonal Antibody · Lymphoma
• Blinatumomab (Blincyto) — Monoclonal Antibody · Leukemia