GSK and Genmab announce topline results from the concluded pivotal trial of Arzerra (ofatumumab) in fludarabine and alemtuzumab refractory chronic lymphocytic leukemia

GlaxoSmithKline (GSK) and Genmab A/S (OMX: GEN) announced today top line results from the concluded pivotal trial of ofatumumab in patients with fludarabine and alemtuzumab refractory chronic lymphocytic leukemia (CLL).

Ofatumumab was given accelerated approval by the US Food and Drug Administration (FDA) on October 26, 2009 for the treatment of patients with CLL who are refractory to fludarabine and alemtuzumab treatment based on the interim results from this trial in 59 patients. On April 19, 2010, the European Commission granted a conditional marketing authorization to Arzerra™ (ofatumumab) for the treatment of chronic lymphocytic leukemia (CLL) in patients who are refractory to fludarabine and alemtuzumab.

A total of 95 patients with fludarabine and alemtuzumab refractory CLL were treated in the study. The objective response rate (ORR), as determine by an Independent Review Committee, in the study was 51%. In addition to the 95 patients in the efficacy analysis, the study also included 128 patients with relapsed or refractory CLL, who were not refractory to both fludarabine and alemtuzumab.

There were no unexpected safety findings reported with the total study population (n=223). The most common adverse reactions (=10%) occurring in patients treated with Arzerra were pyrexia(21%), anemia (18%), diarrhea (17%), neutropenia, fatigue (16%), dyspnea (15%), pneumonia (15%), chills (13%), rash (13%), nausea (13%), bronchitis (12%), peripheral edema (11%), back pain (10%) and upper respiratory tract infection (10%).

Results from this concluded pivotal trial are consistent with the efficacy and safety data reported in the interim analysis and demonstrate the activity of single-agent ofatumumab in patients with fludarabine and alemtuzumab-refractory chronic lymphocytic leukemia.

About ofatumumab

Ofatumumab is a human monoclonal antibody. Ofatumumab binds specifically to both the small and large extracellular loops of the CD-20 molecule. The CD20 molecule is expressed on normal B lymphocytes (pre-B- to mature B-lymphoctye) and on B-cell CLL. In vitro data suggest that possible mechanisms of cell lysis include complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity.

Important Safety Information

Infusion Reactions

ARZERRA can cause serious infusion reactions manifesting as bronchospasm, dyspnea, laryngeal edema, pulmonary edema, flushing, hypertension, hypotension, syncope, cardiac ischemia/infarction, back pain, abdominal pain, pyrexia, rash, urticaria, and angioedema. Infusion reactions occur more frequently with the first 2 infusions. Premedicate with acetaminophen, an antihistamine, and a corticosteroid Interrupt infusion for infusion reactions of any severity. Institute medical management for severe infusion reactions including angina or other signs and symptoms of myocardial ischemia In a study of patients with moderate to severe chronic obstructive pulmonary disease, an indication for which ARZERRA is not approved, 2 of 5 patients developed Grade 3 bronchospasm during infusion. 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.

Cytopenias

Prolonged (=1 week) severe neutropenia and thrombocytopenia can occur with ARZERRA. Monitor complete blood counts (CBC) and platelet counts at regular intervals during therapy, and increase the frequency of monitoring in patients who develop Grade 3 or 4 cytopenias. 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.

Progressive Multifocal Leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML), including fatal PML, can occur with ARZERRA. Consider PML in any patient with new onset of or changes in pre-existing neurological signs or symptoms. Discontinue ARZERRA if PML is suspected, and initiate evaluation for PML including consultation with a neurologist, brain MRI, and lumbar puncture.

Hepatitis B Reactivation

Hepatitis B reactivation, including fulminant hepatitis and death, occurs with other monoclonal antibodies directed against CD20. Screen patients at high risk of hepatitis B virus (HBV) infection before initiation of ARZERRA. Closely monitor carriers of hepatitis B for clinical and laboratory signs of active HBV infection during treatment with ARZERRA and for 6 to 12 months following the last infusion of ARZERRA. Discontinue ARZERRA in patients who develop viral hepatitis or reactivation of viral hepatitis, and institute appropriate treatment. Insufficient data exist regarding the safety of administration of ARZERRA in patients with active hepatitis.

Intestinal Obstruction

Obstruction of the small intestine can occur in patients receiving ARZERRA. Perform a diagnostic evaluation if obstruction is suspected.

Immunizations

The safety of immunization with live viral vaccines during or following administration of ARZERRA has not been studied. Do not administer live viral vaccines to patients who have recently received ARZERRA. The ability to generate an immune response to any vaccine following administration of ARZERRA has not been studied.

Most Common Serious Adverse Reactions

In patients who received an infusion of 2000 mg of ARZERRA, the most common serious adverse reactions were infections (including pneumonia and sepsis), neutropenia, and pyrexia.

Infections

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

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Cautionary statement regarding forward-looking statements
Under the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995, GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Factors that may affect GSK' s operations are described under 'Risk Factors' in the 'Business Review' in the company' s Annual Report on Form 20-F for 2009.