GlaxoSmithKline plc and Genmab announced that the phase III study of ofatumumab (Arzerra) versus physicians’ choice in patients with bulky fludarabine-refractory chronic lymphocytic leukaemia (CLL) did not meet its primary endpoint of progression free survival (PFS). The median PFS, as assessed by the Independent Review Committee, was 5.36 months for of atumumab and 3.61 months for physicians’ choice (Hazard Ratio 0.79, p=0.267).

The result reported is headline data; the full analysis of safety and efficacy data is underway and will be completed in the coming months. This study (OMB114242) was conducted to meet the requirements from the EU Commission for the conditional approval of ofatumumab for the treatment of CLL in patients who are refractory to fludarabine and alemtuzumab. The current indications in the EU or US do not include bulky fludarabine-refractory CLL patients.

“It was our priority to share this result with the scientific community as soon it became available. We will now work to further analyse the data and to better understand the totality of the efficacy and safety findings,” said Dr. Rafael Amado, Head of Oncology R&D at GSK. “We are very grateful to the CLL patients who participated in this trial.”

“Although of atumumab performed broadly in-line with previous data, today’s result is disappointing. Based on this result, we do not anticipate applying for a label expansion for ofatumumab in this specific refractory CLL population,” said Jan van de Winkel, Ph.D., chief executive officer of Genmab.

This phase III open-label study randomised 122 patients with bulky fludarabine-refractory CLL to one of two treatment arms. Patients were randomised to either of atumumab or physicians’ choice (2:1). Patients randomised to ofatumumab received an initial dose of 300 mg, followed 1 week later by 2,000 mg once weekly for 7 weeks, followed 4 weeks later by one infusion of 2,000 mg every 4 weeks for a total treatment duration of 6 to 12 months. Patients in the physicians’ choice arm received a treatment regimen chosen by a physician for up to six months.

The primary endpoint of the study was progression free survival as adjudicated by the Independent Review Committee. Secondary objectives are to evaluate response, overall survival, safety, tolerability and health-related quality of life of subjects treated with of atumumab versus physicians’ choice of treatment.

CLL, the most commonly diagnosed adult leukaemia in Western countries, accounts for approximately one-third of all cases of leukaemia. In the US , it is estimated that more than 105,000 people currently live with or have been previously treated for CLL and an estimated 15,680 new cases of CLL were diagnosed in the past year. The average age of diagnosis is 72 years old, and approximately 90 per cent of patients with CLL are estimated to be over the age of 55.3.  The majority of patients with CLL have at least one comorbidity such as hypertension, diabetes, cardiovascular disease, or COPD.

Of atumumab is a monoclonal antibody that is designed to target the CD20 molecule found on the surface of CLL cells and normal B lymphocytes.

In the US., of atumumab is approved for use in combination with chlorambucil for the treatment of previously untreated patients with CLL for whom fludarabine-based therapy is considered inappropriate. Ofatumumab is also approved for first-line use in Russia.

In more than 50 countries worldwide, ofatumumab is indicated as monotherapy for the treatment of patients with CLL refractory to fludarabine and alemtuzumab.

Of atumumab is being developed under a co-development and collaboration agreement between Genmab and GSK.

Arzerra is a trademark of the GSK group of companies.

GSK one of the world’s leading research-based pharmaceutical and healthcare companies is committed to improving the quality of human life by enabling people to do more, feel better and live longer.

Genmab is a publicly traded, international biotechnology company specialising in the creation and development of differentiated human antibody therapeutics for the treatment of cancer.  Founded in 1999, the company currently has one marketed antibody, Arzerra (of atumumab) for the treatment of certain chronic lymphocytic leukaemia indications, a clinical pipeline with both late and early stage programmes, and an innovative pre-clinical pipeline.