Ofatumumab Now Approved for Use in Relapsed in CLL

Roxanne Nelson, BSN, RN


September 01, 2016

The US Food and Drug Administration (FDA) has approved a supplemental biologics license application (sBLA) for ofatumumab (Arzerra, Genmab/Novartis) for its use in combination with fludarabine and cyclophosphamide for the treatment of patients with relapsed chronic lymphocytic leukemia (CLL).

Ofatumumab has been available in the United States since 2009, when it was initially granted accelerated approval for the treatment of patients with CLL refractory to fludarabine (multiple brands) and alemtuzumab (Campath, Genzyme).

In 2014, the FDA granted full approval to ofatumumab for use in combination with chlorambucil (Leukeran, Aspen Global) for previously untreated patients who are not candidates for fludarabine-based therapy. The drug has a breakthrough therapy designation for this indication.

In the European Union, ofatumumab is approved for use in combination with chlorambucil or bendamustine as well as for CLL patients who have not received prior therapy and who are not eligible for fludarabine-based therapy.

Ofatumumab is a cytolytic monoclonal antibody that binds specifically to the CD20 molecule expressed on the surface of normal and malignant B-lymphocytes, making them more susceptible to an attack from the immune system.

New Indication for Relapsed CLL

"This is the fourth CLL indication approved in the US for Arzerra, and we are pleased to see the availability of this treatment expand to a wider number of patients," said Jan van de Winkel, PhD, chief executive officer of Genmab, in a statement.

The FDA's approval for this indication is based on results of the COMPLEMENT 2 study, a phase 3 open-label, randomized trial of ofatumumab in combination with fludarabine-cyclophosphamide vs fludarabine-cyclophosphamide. That study included 365 patients in 18 countries with relapsed CLL.

Study participants were randomly allocated in a 1:1 ratio to treatment with up to six cycles of ofatumumab in combination with fludarabine and cyclophosphamide or up to six cycles of fludarabine and cyclophosphamide alone. The primary endpoint was progression-free survival (PFS).

The study met the primary endpoint, as it increased PFS by 54% in the group receiving the ofatumumab combination ― 28.9 months vs 18.8 months (hazard ratio = 0.67; P = .0032).

There was also a higher overall response rate (84% vs 68%) with the addition of ofatumumab in comparison with fludarabine and cyclophosphamide alone.

The safety profile observed in this study was consistent with that of other trials of ofatumumab. No new safety signals were observed.

Ofatumumab carries a boxed warning, in that it may cause hepatitis B virus reactivation; high-risk patients should be screened for infection before initiation of therapy. Hepatitis B virus carriers should be closely monitored for signs of active infection during treatment and for 6 to 12 months after discontinuation of therapy. In addition, progressive multifocal leukoencephalopathy resulting in death can occur in patients receiving CD20-directed cytolytic antibodies.


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