Photo courtesy of GSK
The US Food and Drug Administration (FDA) has approved the use of ofatumumab (Arzerra®) in combination with fludarabine and cyclophosphamide to treat patients with relapsed chronic lymphocytic leukemia (CLL).
Ofatumumab was previously approved by the FDA for use in combination with chlorambucil to treat previously untreated CLL patients who cannot receive fludarabine-based therapy, as monotherapy for CLL that is refractory to fludarabine and alemtuzumab, and as maintenance therapy for patients who are in complete or partial response after receiving at least 2 lines of therapy for recurrent or progressive CLL.
Ofatumumab is a monoclonal antibody designed to target CD20.
The drug’s prescribing information includes a boxed warning noting that hepatitis B virus reactivation can occur in patients receiving CD20-directed cytolytic antibodies, including ofatumumab. In some cases, this results in fulminant hepatitis, hepatic failure, and death.
The boxed warning also states that progressive multifocal leukoencephalopathy, resulting in death, can occur in patients receiving CD20-directed cytolytic antibodies, including ofatumumab.
Ofatumumab is marketed under a collaboration agreement between Genmab and Novartis.
COMPLEMENT 2 trial
The FDA’s latest approval for ofatumumab is based on results of the phase 3 COMPLEMENT 2 trial. Novartis reported top-line results from this study in April.
The trial enrolled 365 patients with relapsed CLL. The patients were randomized 1:1 to receive up to 6 cycles of ofatumumab in combination with fludarabine and cyclophosphamide or up to 6 cycles of fludarabine and cyclophosphamide alone.
The primary endpoint was progression-free survival, as assessed by an independent review committee.
The median progression-free survival was 28.9 months for patients receiving ofatumumab plus fludarabine and cyclophosphamide, compared to 18.8 months for patients receiving fludarabine and cyclophosphamide alone (hazard ratio=0.67, P=0.0032).
Novartis said the safety profile observed in this study was consistent with other trials of ofatumumab, and no new safety signals were observed.
