b Complete resolution of constitutional symptoms (fever, night sweats, fatigue, weight loss) defined as the presence of any symptoms at baseline, followed by no symptoms present.

c Lymphadenopathy measured by sum of the products of greatest diameters (SPD) as assessed by physical examination.

Arzerra was also given to a group of patients (n=79) with bulky lymphadenopathy (defined as at least one lymph node > 5cm) who were also refractory to fludarabine. The overall response rate in this group was 47% (99% CI: 32%, 62%). The median progression-free survival was 5.9 months (95% CI: 4.9, 6.4) and the median overall survival was 15.4 months (95% CI: 10.2, 20.2). The response rate in patients with prior rituximab therapy was 44% (95% CI: 29, 60). These patients also experienced comparable clinical improvement, in terms of the efficacy endpoints and haematological parameters detailed above, to patients refractory to both fludarabine and alemtuzumab,

Additionally a group of patients (n=16) who were intolerant/ineligible for fludarabine treatment and/or intolerant to alemtuzumab treatment were treated with Arzerra. The overall response rate in this group was 56% (99% CI: 24%, 85%).

Hx-CD20-402

A dose-ranging study was conducted in 33 patients with relapsed or refractory CLL. Patient median age was 61 years (range: 27 to 82 years), the majority were male (58%), and all were white. Treatment with ofatumumab (when given as 4 once weekly infusions), led to a 50% objective response rate in the highest dose group (1st dose: 500 mg; 2nd, 3rd and 4th dose: 2,000 mg) and included 12 partial remissions and one nodular partial remission. For the highest dose group, the median time to progression was 15.6 weeks (95% CI: 15-22.6 weeks) in the full analysis population, and 23 weeks (CI: 20-31.4 weeks) in responders. The duration of response was 16 weeks (CI: 13.3 – 19.0 weeks) and the time to next CLL therapy was 52.4 weeks (CI: 36.9 – non-estimable).

Paediatric population

The European Medicines Agency has waived the obligation to submit the results of studies with Arzerra in all subsets of the paediatric population in Chronic Lymphocytic Leukaemia (see section 4.2 for information on paediatric use).

5.2 Pharmacokinetic properties

 Absorption

Ofatumumab is administered by intravenous infusion; therefore, absorption is not applicable. Maximum ofatumumab serum concentrations were generally observed at or shortly after the end of the infusion. Pharmacokinetic data were available from 146 patients with refractory CLL. The geometric mean Cmax value was 63 μg/ml after the first infusion (300 mg); after the eighth weekly infusion (seventh infusion of 2,000 mg), the geometric mean Cmax value was 1,482 μg/ml and geometric mean AUC(0-) value was 674,463 μg.h/ml; after the twelfth infusion (fourth monthly infusion; 2,000 mg), the geometric mean Cmax value was 881 μg/ml and geometric mean AUC(0-) was 265,707 μg.h/ml.

Distribution

Ofatumumab has a small volume of distribution,