FDA批准Arzerra用于一线适应症，是基于III期COMPLEMENT1研究的数据。该试验在超过400例既往未经治疗的CLL患者中开展，研究中将ofatumumab+苯丁酸氮芥（chlorambucil）组合疗法与苯丁酸氮芥单药疗法进行了对比。研究结果表明，与苯丁酸氮芥单药疗法相比，组合疗法显著改善了疾病无进展生存期（PFS，22.4个月 vs 13.1个月，p＜0.001）。
英文原文：GSK and Genmab receive FDA approval for Arzerra® (ofatumumab) as first-line treatment in combination with chlorambucil for patients with Chronic Lymphocytic Leukaemia (CLL) for whom fludarabine-based therapy is considered inappropriate
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.1
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).1
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).1
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.1
About Arzerra (ofatumumab) Arzerra (ofatumumab) is a CD20-directed monoclonal antibody indicated in combination with chlorambucil for the treatment of previously untreated patients with chronic lymphocytic leukaemia (CLL) for whom fludarabine-based therapy is considered inappropriate.1 Arzerra is also indicated as monotherapy for the treatment of patients with CLL refractory to fludarabine and alemtuzumab.1 Ofatumumab is being developed under a co-development and collaboration agreement between Genmab and GSK. Arzerra is a registered trademark of the GSK group of companies.