Arzerra（商标）（ofatumumab）批准用于治疗慢性淋巴细胞白血病

美国FDA已经批准Arzerra（ofatumumab，由葛兰素史克和Genmab公司），一种单克隆抗体，用于治疗慢性淋巴细胞白血病（CLL）是耐火材料氟达拉滨的Genzyme公司 （ 氟达拉滨 ，）和阿来组单抗（ 坎帕斯的Genzyme公司 ，）治疗。 Arzerra was approved under the FDA\'s accelerated approval process based on results from a pivotal study in
which 42% of patients with CLL who were refractory to both fludarabine and alemtuzumab responded to treatment with Arzerra.
Arzerra批准下，FDA的审批程序加速成果的基础上，从一个关键的研究，其中42％的患者与慢性淋巴细胞白血病难治谁是既氟达拉滨和阿来组单抗反应与Arzerra治疗。
 
A median duration of response of 6.5 months was observed.阿的6.5个月的中位缓解时间观察。

GlaxoSmithKline is currently conducting a clinical trial in CLL patients to confirm that the addition of Arzerra to standard chemotherapy delays the progression of the disease.

葛兰素史克公司正进行在CLL患者的临床试验证实，Arzerra除了标准的化疗，延误了疾病的进展。

Arzerra is expected to be available in mid-November 2009. Arzerra预计可于11月中旬2009。

丹麦Genmab制药公司公布了其在研新药Arzerra在一项中期临床实验中获得的首批数据，该药主要用于从未接受过任何治疗的慢性淋巴细胞白血病（CLL）患者，由Genmab和GSK共同研发。

在上述实验中，受试者为61名CLL患者，他们采用Arzerra+Fludarabine（氟达拉宾）+ Cyclophosphamide（环磷酰胺）进行治疗。实验结果发现，采用500毫克Arzerra治疗的患者病情完全缓解率为32%，而采用1000毫克剂量的患者病情完全缓解率达到50%。此外，500毫克剂量受试组用药后总体应答率为77%，1000毫克剂量受试组对药物的总体应答率为73%。

Genmab公司表示，在为期30天用药过程中未出现意料之外的安全性问题，该药最常见的副作用为嗜中性白血球减少（出现几率为48%），其他常见不良反应（出现几率为15%）还包括恶心呕吐、皮疹、发热、头痛和血小板减少。

两个不同剂量受试组用药后出现上述不良反应的概率相当。其中有一位患者在实验过程中死亡，经调查人员核查之后证实该患者的死亡与Arzerra没有关联。

Arzerra (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 standardtreatments

GlaxoSmithKline (GSK) and Genmab A/S (OMX: GEN)announced today positive results from a pivotal trial pre-planned interim analysis of Arzerra
(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[8225;]).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 (≥10%)werepyrexia,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 Ouml;sterborg, DepartmentofHematology, KarolinskaHospital, 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 sufferingfromhematological 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 makes 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 distinct 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 study1

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-developmentandcommercialization 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]