Ofatumumab

Ofatumumab is a human monoclonal antibody which targets an epitope in the CD20 molecule encompassing parts of the small and large extracellular loops. Ofatumumab directs the body's immune system to fight normal and cancerous B-cells. Ofatumumab attaches to the CD20 molecule, which is found on the surface of B-cells, the type of cell which becomes cancerous in chronic lymphocytic leukemia (CLL). The CD20 molecule is also found on over 90% of B-cell lymphomas, as well as other lymphoid tumors of B-cell origin. In types of cancer such as these, B-cells can over-proliferate and treatment is needed to reduce their number. 

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. 

Ofatumumab is being investigated for use in other oncology and autoimmune diseases including CLL, follicular lymphoma (FL) and relapsing multiple sclerosis (RMS). Other areas where a CD20 antibody might be used include Crohn's disease, Wegener's Granulomatosis, other B-cell lymphomas, including mantle cell lymphoma.

Ofatumumab is marketed and developed under a co-development and commercialization agreement with Novartis Pharma AG. Ofatumumab was originally developed under an agreement with GlaxoSmithKline (GSK). Refer to our Current partnerships page for more information.

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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. 

First-line CLL
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%.  

Refractory CLL
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). 

Relapsed CLL
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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Follicular lymphoma (FL) is a slow growing cancer of the B-cells, accounting for about 20% of non-Hodgkin's lymphomas (NHL) and 70% of all indolent NHL1.  The estimated number of new cases of FL in 2015 in the U.S and five major European markets was 24,391. This estimate increases to 28,528 in 20232. The median survival for patients with FL ranges from eight to fifteen years, with a 62% ten-year relative survival rate1.

Ofatumumab is being investigated in a clinical study in NHL. For more information, visit clinicaltrials.gov.


1 GlobalData. Non-Hodgkin's B-Cell Lymphoma: Opportunity Analysis and Forecast to 2018. Published August 2014
2 GlobalData. EpiCast Report: Non-Hodgkin's Lymphoma - Epidemiology Forecast to 2023. Published May 2014


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Multiple Sclerosis (MS) is an inflammatory disease of the central nervous system that affects approximately 2.5 million people worldwide1. The etiology of MS remains unknown, but the geographic variation points towards possible environmental and genetic factors. The most common form of MS, accounting for 80% of cases2 is relapsing remitting MS (RRMS) characterized by unpredictable recurrent attacks where the symptoms usually evolve over days and are followed by either complete, partial or no neurological recovery. No progression of neurological impairment is experienced between attacks. 

A Phase II study for RRMS investigating the subcutaneous formulation of ofatumumab has been completed and Phase III studies in relapsing MS are underway. For more information on ofatumumab clinical studies in MS, visit clinicaltrials.gov.

1GlobalData. EpiCast Report: Multiple Sclerosis - Epidemiology Forecast to 2024. Published September 2015
2 Datamonitor. Multiple Sclerosis Treatment. Published January 2015

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