SIDE EFFECTS

The following serious adverse reactions are discussed in greater detail in other sections of the labeling:

• Infusion Reactions [see WARNINGS AND PRECAUTIONS]
• Cytopenias [see WARNINGS AND PRECAUTIONS]
• Progressive Multifocal Leukoencephalopathy [see WARNINGS AND PRECAUTIONS]
• Hepatitis B Reactivation [see WARNINGS AND PRECAUTIONS]
• Intestinal Obstruction [see WARNINGS AND PRECAUTIONS]

The most common adverse reactions ( ≥ 10%) in Study 1 were neutropenia, pneumonia, pyrexia, cough, diarrhea, anemia, fatigue, dyspnea, rash, nausea, bronchitis, and upper respiratory tract infections.

The most common serious adverse reactions in Study 1 were infections (including pneumonia and sepsis), neutropenia, and pyrexia. Infections were the most common adverse reactions leading to drug discontinuation in Study 1.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of monotherapy with ARZERRA was evaluated in 181 patients with relapsed or refractory CLL in 2 open-label, non-randomized, single-arm studies. In these studies, ARZERRA was administered at 2,000 mg beginning with the second dose for 11 doses (Study 1 [n = 154]) or 3 doses (Study 2 [n = 27]).

The data described in Table 2 and other sections below are derived from 154 patients in Study 1. All patients received 2,000 mg weekly from the second dose onward. Ninety percent of patients received at least 8 infusions of ARZERRA and 55% received all 12 infusions. The median age was 63 years (range: 41 to 86 years), 72% were male, and 97% were White.

Table 2: Incidence of All Adverse Reactions Occurring in ≥ 5% of Patients in Study 1 and in the Fludarabine- and Alemtuzumab-Refractory Subset of Study 1 (MedDRA 9.0)

Infusion Reactions

Infusion reactions occurred in 44% of patients on the day of the first infusion (300 mg), 29% on the day of the second infusion (2,000 mg), and less frequently during subsequent infusions.

Infections

A total of 108 patients (70%) experienced bacterial, viral, or fungal infections. A total of 45 patients (29%) experienced ¡ÝGrade 3 infections, of which 19 (12%) were fatal. The proportion of fatal infections in the fludarabine- and alemtuzumab-refractory group was 17%.

Neutropenia

Of 108 patients with normal neutrophil counts at baseline, 45 (42%) developed ≥ Grade 3 neutropenia. Nineteen (18%) developed Grade 4 neutropenia. Some patients experienced new onset Grade 4 neutropenia > 2 weeks in duration.

Immunogenicity

There is a potential for immunogenicity with therapeutic proteins such as ofatumumab. Serum samples from patients with CLL in Study 1 were tested by enzyme-linked immunosorbent assay (ELISA) for anti-ofatumumab antibodies during and after the 24-week treatment period. Results were negative in 46 patients after the 8th infusion and in 33 patients after the 12th infusion.

Immunogenicity assay results are highly dependent on several factors including assay sensitivity and specificity, assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to ARZERRA with the incidence of antibodies to other products may be misleading.

Read the entire FDA prescribing information for Arzerra (Ofatumumab Injection) »