GlaxoSmithKline plc and Genmab announced that an Independent Data Monitoring Committee (IDMC) interim analysis of a phase III study, PROLONG (OMB 112517), reached the predefined significance level for efficacy (p=0.001). The interim analysis demonstrated that treatment with ofatumumab (Arzerra) met the primary endpoint of improving progression free survival (PFS). The study evaluated ofatumumab maintenance therapy versus no further treatment (observation) in patients with relapsed chronic lymphocytic leukaemia (CLL) who responded to treatment at relapse.

The IDMC did not identify any new safety signals and will continue to monitor patients for safety until all study patients complete therapy. Further analysis of the safety and efficacy data is underway and will be shared with regulators and the scientific community in the coming months.

“This interim result from the PROLONG study demonstrated that maintenance therapy with ofatumumab lowered the risk of disease progression in patients who responded to treatment at relapse. We look forward to sharing the results of the interim analysis with regulatory agencies to evaluate the potential for future regulatory filings,” said Dr. Rafael Amado, Head of Oncology R&D, GSK.

“We are very pleased that this study of ofatumumab, the first phase III study to evaluate maintenance therapy for relapsed CLL, met the primary endpoint at the interim analysis. This result indicates the potential of ofatumumab in this setting where there are currently no approved treatments. We look forward to presenting the detailed data from this study at a future medical conference,” said Jan van de Winkel, PhD, chief executive officer of Genmab.

This pivotal phase III study was designed to randomise up to 532 patients with relapsed CLL who have responded to treatment at relapse, to either ofatumumab maintenance treatment or no further treatment (observation). Patients in the ofatumumab arm receive an initial dose of 300 mg of ofatumumab, followed one week later by a second dose of 1,000 mg, then doses of 1,000 mg every 8 weeks for up to two years, while patients in the observation treatment arm receive no further treatment.

The primary endpoint of the study is PFS. Secondary objectives will evaluate clinical benefit, safety, tolerability, the health-related quality of life of subjects treated with ofatumumab versus no further treatment, and pharmacokinetics among relapsed CLL patients receiving maintenance therapy with ofatumumab.

CLL, the most commonly diagnosed adult leukaemia in western countries, accounts for approximately one-third of all cases of leukaemia. In the USA, 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.3  The average age of diagnosis is 72 years, and approximately 90 per cent of patients with CLL are estimated to be over the age of 55 years  The majority of patients with CLL have at least one comorbidity such as hypertension, diabetes, cardiovascular disease, or COPD.

Ofatumumab—a monoclonal antibody that is designed to target the CD20 molecule found on the surface of CLL cells and normal B lymphocytes—is not approved or licensed anywhere in the world as maintenance treatment for relapsed CLL.In the USA, ofatumumab 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. In the EU, ofatumumab is approved for use 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 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.

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