Ofatumumab Approved for Advanced CLL

Kate Traynor

BETHESDA, MD 27 October 2009—Ofatumumab, a cytolytic CD-20 monoclonal antibody product from GlaxoSmithKline and Genmab A/S, has been licensed for the treatment of chronic lymphocytic leukemia (CLL) in patients whose cancer does not respond to other chemotherapy, FDA announced late yesterday.

The product will be marketed as Arzerra and should be available "in the coming weeks," according to the companies.

CLL is a slowly progressing form of leukemia that primarily affects older adults and is the most common type of leukemia that affects adults, according to the National Cancer Institute (NCI).

The FDA-approved labeling (PDF) for ofatumumab states that the drug is indicated for the treatment of CLL in patients whose disease does not respond to treatment with fludarabine and alemtuzumab.

Ofatumumab was licensed under an accelerated approval mechanism that allows drugs for unmet medical needs to reach the market earlier than normal and on the basis of indirect indications of clinical benefit.

None of the patients with refractory CLL who participated in a clinical trial of ofatumumab had a "complete response" to the therapy, according to the drug's labeling. Overall, an i.v. treatment regimen of ofatumumab induced a 42% objective tumor response rate as defined by NCI guidelines for the treatment of CLL. The median duration of the response was 6.5 months.

According to FDA, additional clinical trials are being conducted to determine whether ofatumumab therapy delays the progression of CLL.

The most frequent adverse events reported by clinical trial participants included neutropenia, anemia, pneumonia, fever, cough, rash, upper-respiratory-tract infection, and gastrointestinal symptoms. Serious infusion reactions, blood disorders, intestinal obstruction, and infection, including progressive multifocal leukoencephalopathy and reactivation of hepatitis B virus infection, were also reported during clinical trials of ofatumumab.

The labeling recommends that patients be premedicated with acetaminophen, an antihistamine, and a corticosteroid to decrease the risk of infusion reactions during the administration of ofatumumab.

Live vaccines should not be administered to patients undergoing treatment with ofatumumab.

The recommended dosage of ofatumumab is a 300-mg initial dose administered by i.v. infusion, followed by 2000 mg weekly for seven doses. Four weeks later, treatment should resume with a total of four 2000-mg doses administered every four weeks. A full treatment regimen consists of 12 doses.

Instructions for preparing and administering the recommended amounts ofatumumab are included in the drug's labeling. Ofatumumab will be available in packages containing 3 or 10 100-mg, 20-mg/mL single-use vials and two inline filters. The vials should be refrigerated and protected from light.