About FDA


On October 26, 2009 the U.S. Food and Drug Administration granted accelerated approval to ofatumumab (Arzerra, GlaxoSmithKline) for the treatment of patients with chronic lymphocytic leukemia (CLL) refractory to fludarabine and alemtuzumab.  The approval was based on a clinically meaningful and durable overall response rate (ORR) observed in a single-arm trial (Hx-CD20-406).  As a condition of accelerated approval, subsequent randomized trials are required to verify and describe the clinical benefit of ofatumumab in CLL.

Hx-CD20-406 was a single‑arm, multicenter trial in 154 patients with relapsed or refractory CLL.  Accelerated approval was based on the results of a pre-specified subgroup of 59 patients who were refractory to both fludarabine and alemtuzumab.  Drug refractoriness was defined as failure to achieve at least a partial response to, or disease progression within 6 months of the last dose of fludarabine or alemtuzumab.  The primary efficacy outcome was durable ORR as determined by the 1996 National Cancer Institute Working Group (NCIWG) Guidelines for CLL.

In the Hx-CD20-406 trial, patients received an initial 300 mg dose, followed 1 week later by 2,000 mg weekly for 7 doses, followed 4 weeks later by 2,000 mg every 4 weeks for 4 doses (maximum of 12 doses).  All doses were administered by intravenous infusion.

In patients with CLL refractory to both fludarabine and alemtuzumab, the median age was 64 years (range 41 to 86 years), 75% were male and the median number of prior therapies was 5.  Eighty-eight percent received at least 8 ofatumumab infusions and 54% received 12 ofatumumab infusions. 

The investigator‑determined ORR in patients with CLL refractory to fludarabine and alemtuzumab was 42% (99% CI: 26, 60) with a median response duration of 6.5 months (95% CI: 5.8, 8.3).  There were no complete responses.  Supportive information included anti‑tumor activity observed in a multicenter, open‑label, dose-escalation study (Hx-CD20-402) conducted in patients with relapsed or refractory CLL and additional patients enrolled in the Hx-CD20-406 trial.

The safety of single-agent ofatumumab was evaluated in 181 patients with relapsed or refractory CLL enrolled in either study Hx-CD20-406 or Hx-CD20-402.  Ofatumumab was administered at 2,000 mg beginning with the second dose for 11 doses in Hx-CD20-406 (154 patients) or 3 doses in Hx-CD20-402 (27 patients).

The most common adverse reactions (>10%) in the Hx-CD20-406 trial were neutropenia, pneumonia, pyrexia, cough, diarrhea, anemia, fatigue, dyspnea, rash, nausea, bronchitis, and upper respiratory tract infections. The most common adverse reaction leading to drug discontinuation was infection.

In the Hx-CD20-406 trial, infusion reactions occurred in 44% of patients on the day of the first infusion (300 mg) and 29% on the day of the second infusion (2,000 mg) and less frequently during subsequent infusions.  The most common serious adverse reactions in this study were infections (including pneumonia and sepsis), neutropenia, and pyrexia.  A total of 45 patients (29%) experienced grade 3 or greater infections; 19 (12%) were fatal.  Of 108 patients with normal baseline neutrophil counts, 45 (42%) developed grade 3 or greater neutropenia. Nineteen patients (18%) developed grade 4 neutropenia.  One patient developed fatal progressive multifocal leukoencephalopathy after ofatumumab treatment. 

Full prescribing information, including clinical trial information, safety, dosing, drug-drug interactions and contraindications is available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/125326lbl.pdf



Page Last Updated: 12/23/2015
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