Chronic Lymphocytic Leukemia (CLL) is a cancer in which the bone marrow produces too many white blood cells called lymphocytes. It is the most common form of leukemia in the western world1 and usually occurs during or after middle age. At present, no curative chemotherapy is available. Approximately 39,295 new cases of CLL were forecast in the U.S. and the five major European markets in 2015, increasing to 45,683 new cases in 20231. Prognosis is relatively good with a five-year survival rate of 64% to 83% in the U.S. and five major European markets.
Ofatumumab is being studied in numerous clinical trials for CLL as well as other cancer and autoimmune diseases. For more information on ofatumumab clinical trials, visit clinicaltrials.gov. Ofatumumab is also being investigated in numerous Investigator Sponsored Studies (ISS). For more information on ISS studies, visit clinicaltrials.gov.
Ofatumumab is approved approved to treat chronic lymphocytic leukemia (CLL) patients who are refractory to fludarabine and alemtuzumab in all major markets. In the United States ofatumumab is also approved in the following indications:
- in combination with chlorambucil to treat previously untreated patients with CLL for whom fludarabine-based therapy is considered inappropriate;
- for extended treatment of patients who are in complete or partial response after at least two lines of therapy for recurrent or progressive CLL; and
- in combination with fludarabine and cyclophosphamide (FC) for the treatment of patients with relapsed CLL.
Ofatumumab is also approved in Europe in combination with chlorambucil or bendamustine for the treatment of patients with CLL who have not received prior therapy and who are not eligible for fludarabine-based therapy.
In April 2014, the US Food and Drug Administration (FDA) approved the use of Arzerra in combination with chlorambucil for the treatment of previously untreated patients with CLL for whom fludarabine-based therapy is considered inappropriate. In July 2014, EU authorization was granted for the use of Arzerra in combination with chlorambucil or bendamustine for the treatment of patients with CLL who have not received prior therapy and who are not eligible for fludarabine-based therapy.
The approvals were based on results from a Phase III study (COMPLEMENT 1) evaluating the combination of Arzerra and chlorambucil (N=221) versus chlorambucil alone (N=226) which demonstrated statistically significant improvement in median progression free survival (PFS) in patients randomized to Arzerra and chlorambucil compared to patients randomized to chlorambucil alone (22.4 months versus 13.1 months, respectively) (HR=0.57 [95% CI, 0.45, 0.72] p<0.001).
The EU approval was also based on results from a Phase II study evaluating Arzerra in combination with bendamustine in 44 patients with previously untreated CLL for whom fludarabine-based treatment was considered inappropriate. Results of this study demonstrated that Arzerra in combination with bendamustine provided an overall response rate (ORR) of 95% (95% CI, 85, 99) and a complete response rate (CR) of 43%.
Arzerra is marketed to treat CLL in patients who are refractory to fludarabine and alemtuzumab in all major markets. The approval was based on interim results from a pivotal study of 154 patients; 59 patients with CLL refractory to fludarabine and alemtuzumab comprised the efficacy population. The ORR of 42% (all partial responses; no complete responses) and median duration of response of 6.5 months applies to the 59 patients.
Extended Treatment for Recurrent or Progressive CLL
In January 2016, the U.S. FDA approved the use of Arzerra for extended treatment of patients who are in complete or partial response after at least two lines of therapy for recurrent or progressive CLL. This approval was based on data from the Phase III study PROLONG (OMB114517), evaluating ofatumumab maintenance therapy versus no further treatment (observation) in patients with relapsed CLL who responded to induction treatment at relapse (N=474). Results from the study showed that patients who received ofatumumab maintenance treatment lived 14.2 months longer without their disease worsening than patients who received no further treatment. Median PFS as assessed by the investigators was 29.4 months for the ofatumuamb treatment arm and 15.2 months for the observation arm (Hazard Ratio 0.50; p<0.0001).
In August 2016, the U.S. FDA approved the use of ofatumumab (Arzerra®) in combination with fludarabine and cyclophosphamide (FC) for the treatment of patients with relapsed CLL. This approval is based on results from the Phase III COMPLEMENT 2 study that evaluated ofatumumab in combination with FC versus FC alone in patients with relapsed CLL (N=365). Results from the study showed a median progression free survival in patients receiving ofatumumab in combination with FC of 28.9 months, compared to 18.8 months in patients receiving FC alone (HR =0.67, p=0.0032).
Safety Information for ofatumumab
The overall safety profile of Arzerra in CLL (previously untreated and relapsed or refractory) is based on data from more than 3,500 patients treated alone or in combination with other therapies in clinical trials.
The most common side effects for Arzerra include adverse events associated with infusion reactions, cytopenias (neutropenia, anemia, thrombocytopenia), and infections (lower respiratory tract infection, including pneumonia, upper respiratory tract infection, sepsis, including neutropenic sepsis and septic shock, herpes virus infection, urinary tract infection).
Please consult the full European Summary of Product Characteristics and full U.S. Prescribing information, including Boxed Warning, for all the labeled safety information for Arzerra.
1 GlobalData, EpiCast Report: Chronic Lymphocytic Leukemia Epidemiology Forecast to 2023. Published May 2014.
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