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Arzerra(TM) (ofatumumab) Demonstrates High Response Rates in Patients With Fludarabine Refractory Chronic Lymphocytic Leukemia (CLL)

Data from a pivotal trial suggests that ofatumumab has activity in heavily pre-treated patients who have failed standard treatments

PHILADELPHIA, Dec. 8 /PRNewswire-USNewswire/ -- GlaxoSmithKline (GSK) and Genmab A/S (OMX: GEN) announced today positive results from a pivotal trial pre-planned interim analysis of Arzerra(TM) (ofatumumab) in the treatment of refractory chronic lymphocytic leukemia (CLL). The results demonstrate the potential of ofatumumab for heavily pre-treated patients with CLL who do not respond to, or for whom currently available treatment options are not appropriate.(1) This research is being presented at the 50th Annual Meeting of the American Society of Hematology, 6-9 December, 2008. Ofatumumab is an investigational drug that has not been approved for any indication in any market at this time.

The analysis included 138 patients with CLL who showed limited or no response (refractory) to both fludarabine and alemtuzumab treatment (double refractory; DR), and patients who were refractory to fludarabine and considered inappropriate candidates for alemtuzumab due to bulky tumor masses in their lymph nodes (bulky fludarabine refractory; BFR).

The primary endpoint of the study was assessment of objective response.* The overall objective response rate seen in these patient groups treated with ofatumumab monotherapy was 58 percent for the DR group (n=59) and 47 percent for the BFR group (n=79); all responding patients had a partial remission (PR**) except for one patient with a complete remission (CR***).(1) Median overall survival was 13.7 months for the DR group and 15.4 months for the BFR group;(1) response to ofatumumab treatment significantly correlated with longer patient survival. The median length of time that a patient lived without their disease getting worse (progression free survival) was 5.7 months for the DR group and 5.9 months for the BFR group.(1)

The most common adverse events seen were infusion related reactions, which were mostly mild to moderate in severity. The most common serious adverse events (Grade 3 or 4) were infections (25 percent in DR; 25 percent in BFR), including one case of progressive multifocal leukoencephalopathy (PML) in a patient with progressive disease. Early death (within eight weeks from start of treatment) occurred in four patients (7 percent) in the DR group and two patients (3 percent) in the BFR group. Tumor lysis syndrome was also reported following treatment with ofatumumab. Common adverse reactions (greater than or equal to 10%) were pyrexia, cough, diarrhea, rash, neutropenia, fatigue, pneumonia, anemia, dyspnea, nausea, and upper respiratory tract infection. No patient tested positive for antibodies to ofatumumab.(1)

"There is a great unmet medical need among patients with CLL that is refractory to conventional therapy. The clinical responses and the tolerability profile we are seeing with ofatumumab in this group of CLL patients are very encouraging," said lead investigator Professor Anders Osterborg, Department of Hematology, Karolinska Hospital, Stockholm, Sweden.

In a post hoc, subset analysis prior treatment with rituximab did not have a significant effect on ofatumumab treatment efficacy. Of those patients who had received prior rituximab-containing therapy 54 percent in the DR group and 44 percent in the BFR group responded to treatment with ofatumumab.(1)

"The positive results seen in this interim analysis reinforce the potential of ofatumumab in the treatment of CLL refractory to standard treatments," said Moncef Slaoui, Chairman Research and Development at GSK. "We are committed to the development of ofatumumab in both CLL and other disease settings to provide an additional treatment option to patients suffering from hematological malignancies."

"Ofatumumab has helped responding patients who did not have other recognized treatment options," said Lisa N. Drakeman, Chief Executive Officer of Genmab. "We are working together with GSK to bring this urgently needed new medicine to market as quickly as possible, and are currently collaborating on filing submissions."

Genmab and GSK now expect to file a Biologics License Application (BLA) filing with the US FDA in January 2009.

CLL is the most common form of leukemia in the Western world,(2) and the treatment of patients with refractory disease remains a significant challenge. Patients who have not responded to current standard therapies, specifically patients whose disease is refractory to fludarabine and alemtuzumab treatment or patients who are refractory to fludarabine but whose diseases make them inappropriate for treatment with alemtuzumab, experience poorer outcomes. Only about 20 percent of patients respond to available salvage therapies.(3) Currently there is no approved drug for the treatment of this patient population.

Ofatumumab is an investigational monoclonal antibody that targets a membrane-proximal (close to the cell surface), small loop epitope (a portion of a molecule to which an antibody binds) on the CD20 molecule on B cells.(4) This epitope is different from the binding sites targeted by other CD20 antibodies currently available or in development.(5) The CD20 molecule is a key target in CLL therapy because it is expressed in most B-cell malignancies.(6)

About the study(1)

The study includes patients with CLL refractory to both fludarabine and alemtuzumab, and patients who are refractory to fludarabine and considered inappropriate candidates for alemtuzumab due to bulky tumor masses in their lymph nodes. The study design calls for patients to receive eight weekly infusions of ofatumumab, followed by four monthly infusions. Patients receive 300 mg of ofatumumab at the first infusion and 2,000 mg of ofatumumab at each subsequent infusion. Disease status is assessed every four weeks until week 28 and then every three months until disease progression or month 24.

The interim analysis included 138 treated patients (DR, n=59; BFR, n=79). Patient recruitment is ongoing and a final analysis will be conducted on the full study population, expected to be 100 patients in each group.

The primary endpoint of the study is objective response over a 24 week period from start of treatment as assessed according to the National Cancer Institute Working Group guidelines by an Independent endpoint Review Committee (IRC). Secondary endpoints included duration of response, progression free survival, time to next CLL therapy, overall survival and adverse events.

About ofatumumab

Ofatumumab is being developed to treat chronic lymphocytic leukemia, follicular non-Hodgkin's lymphoma, diffuse large B-cell lymphoma, rheumatoid arthritis and relapsing-remitting multiple sclerosis under a co-development and commercialization agreement between Genmab and GlaxoSmithKline. It is not yet approved for any indication in any country.

About CLL

CLL is the most common leukemia and one of the most common malignant lymphoid diseases.(2) Globally, leukemia accounts for some 300,000 new cases each year (2.8 percent of all new cancer cases) and 222,000 deaths.(7)

Conference Call

Genmab will hold a conference call to discuss these results tomorrow, December 9, 2008 at:

3:00 pm CEST

2:00 pm BST

9:00 am EST

The conference call will be held in English.

The dial in numbers are as follows:

+1 877 723 9518 (in the US) and ask for the Genmab conference call

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To listen to a live webcast of the call please visit

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About Genmab A/S -- Genmab is a leading international biotechnology company focused on developing fully human antibody therapeutics for unmet medical needs. Using cutting-edge antibody technology, Genmab's world class discovery, development and manufacturing teams have created and developed an extensive pipeline of products for potential treatment of a variety of diseases including cancer and autoimmune disorders. As Genmab advances towards a commercial future, we remain committed to our primary goal of improving the lives of patients who are in urgent need of new treatment options. For more information on Genmab's products and technology, visit

Notes to Editors:

Refractory - term used to describe a disease that does not respond to treatment or returns within six months of completing such treatment

Bulky tumors - when individual tumor masses are >5cm in diameter

Salvage therapy - a final treatment for people who are non-responsive to or cannot tolerate other available therapies for a particular condition and whose prognosis is often poor

Arzerra(TM) is the proposed registered trademark to be used in the United States and Europe.

To access the latest GSK Oncology media materials, visit

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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 2007.

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(*) The percentage of patients whose tumor shrinks or disappears after treatment

(**) A decrease in the extent of cancer in the body, in response to treatment

(***) The disappearance of all signs of cancer in response to treatment.


(1) Osterborg A, Kipps et al. Ofatumumab (HuMax-CD20), a Novel CD20 Monoclonal Antibody, Is An Active Treatment for Patients with CLL Refractory to Both Fludarabine and Alemtuzumab or Bulky Fludarabine-Refractory Disease: Results from the Planned Interim Analysis of An International Pivotal Trial. Abstract #328. Presented at the American Society of Hematology Annual Meeting 2008

(2) Shanafelt TD, Byrd JC, et al. Narrative review: initial management of newly diagnosed, early-stage chronic lymphocytic leukemia. Ann Intern Med. 2006 Sep 19;145(6):435-47.

(3) Tam CS, O'Brien S, et al. The natural history of fludarabine-refractory chronic lymphocytic leukemia patients who fail alemtuzumab or have bulky lymphadenopathy. Leukemia and Lymphoma 2007;48(10):1931-1939

(4) Hagenbeek A, Gadeberg O, et al. First clinical use of ofatumumab, a novel fully human anti-CD20 monoclonal antibody in relapsed or refractory follicular lymphoma: results of a phase 1/2 trial. Blood, 2008; 111: 5486-5495

(5) Teeling JL, Mackus, W,J., et al. The Biological Activity of Human CD20 Monoclonal Antibodies Is Linked to Unique Epitopes on CD20. J Immunol 2006; 177: 362-371

(6) Glennie MJ, French RR, et al. Mechanisms of killing by anti-CD20 monoclonal antibodies. Molecular Immunology, 2007;44 (16):3823-3837

(7) Parkin DM, Bray F, et al. Global Cancer Statistics, 2002. CA Cancer J Clin 2005; 55:74-108

SOURCE GlaxoSmithKline
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