GlaxoSmithKline plc (LSE: GSK) and Genmab A/S (OMX: GEN) announced today that the U.S. Food and Drug Administration (FDA) has approved a Supplemental Biologic License Application (sBLA) for the use of Arzerra® (ofatumumab), a CD20-directed cytolytic monoclonal antibody, in combination with chlorambucil for the treatment of previously untreated patients with chronic lymphocytic leukaemia (CLL) for whom fludarabine-based therapy is considered inappropriate.
The FDA approval of the first-line indication is based on results from a Phase III study (COMPLEMENT 1) which demonstrated statistically significant improvement in median progression-free survival (PFS) in patients who received the combination of ofatumumab and chlorambucil compared to patients who received chlorambucil alone.
"CLL is the most common form of leukaemia amongst adults in Western countries, many of whom are elderly with multiple health issues," said Dr. Paolo Paoletti, President of Oncology, GSK. "Today's approval by the FDA for the use of Arzerra in the first-line setting means that appropriate patients with CLL have a new treatment option."
"We are pleased that Arzerra has been shown to provide clinical benefit and will now be available in the first-line setting. Arzerra, the first approved therapeutic created by Genmab and developed in collaboration with GSK, is the only therapeutic CD20 antibody approved in combination with chlorambucil for first-line CLL and as a monotherapy for CLL refractory to fludarabine and alemtuzumab," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.
The results from COMPLEMENT 1, the randomised, open-label, parallel-arm, pivotal Phase III study evaluating the combination of ofatumumab and chlorambucil (N=221) versus chlorambucil alone (N=226) demonstrated statistically significant improvement in median PFS in patients randomised to ofatumumab and chlorambucil compared to patients randomised to chlorambucil alone (22.4 months versus 13.1 months, respectively) (HR=0.57 [95 per cent CI, 0.45, 0.72] p<0.001).
The majority of adverse reactions (ARs) were Grade 2 or lower in both treatment arms. The most common (≥5 per cent in the ofatumumab plus chlorambucil arm and also ≥2 per cent more than in the chlorambucil monotherapy arm) non-infusion-related ARs (all grades) as reported by investigators within 60 days following the last treatment were neutropaenia (27 per cent ofatumumab + chlorambucil, 18 per cent chlorambucil), asthaenia (8 per cent, 5 per cent), headache (7 per cent, 3 per cent), leukopaenia (6 per cent, 2 per cent), herpes simplex (6 per cent, 4 per cent), lower respiratory tract infection (5 per cent, 3 per cent), arthralgia (5 per cent, 3 per cent), and upper abdominal pain (5 per cent, 3 per cent).
Infusion reactions (IRs) were seen in 67 per cent of patients in the ofatumumab plus chlorambucil arm. Ten per cent of IRs were Grade 3 or greater. IRs that were Grade 3 or greater, serious or led to treatment interruption or discontinuation occurred most frequently with Cycle 1 and decreased with subsequent infusions.