Gazyva(obinutuzumab)注射液药物是第一个具有突破性的治疗指定获得FDA批准
优先审评，孤儿产品指定
美国食品药品管理局（FDA）批准Gazyva(Obinutuzumab)与苯丁酸氮芥联合用药用于治疗之前未经处理的慢性淋巴细胞性白血病(CLL)。CLL是一种血液及骨髓疾病，该疾病通常会慢慢恶化。根据美国国家癌症研究所提供的信息，今年将有15680美国人被确诊患有这种疾病，而4580人将会死于这种疾病。Gazyva通过帮助免疫系统中某些细胞攻击癌症细胞而起作用。
Gazyva是首款以突破性治疗药物资格获得FDA批准的药物。FDA也授予了Gazyva优先审评资格，因为这款药物证实其对严重病症的治疗，在安全性和有效性上有可能会带来明显的改善。并且，由于这款药物也可用于治疗一种罕见疾病，从而获得FDA授予的孤儿药资格。
Gazyva获批用于治疗CLL是基于一项由356名受试者参与的随机、非盲、多中心临床研究，该试验研究在之前未经治疗的CLL受试者身上将Gazyva与瘤可宁合并用药与瘤可宁单独用药进行了对比。Gazyva与瘤可宁合并用药患者的疾病无进展生存期有明显增加，平均增加23个月，而瘤可宁单独用药患者的疾病无进展生存期仅增加11.1个月。
Gazyva与苯丁酸氮芥合并用药患者中所观察到的最常见副作用有输注相关反应、抗感染的白细胞降低(中性粒细胞减少症)、血液中血小板水平降低(血小板减少症)、红细胞水平降低(贫血)、肌肉疼和骨骼痛骼(肌肉骨骼疼痛)和发烧(发热)。
批准日期：2013年11月1日；公司：Genentech、
美国初次批准：2013
适应证和用途
GAZYVA(obinutuzumab)是一种针对CD20溶细胞抗体和适用于与苯丁酸氮芥[chlorambucil]联用，为有既往未治疗过慢性淋巴性白血病患者的治疗。
剂量和给药方法
（1）用糖皮质激素，对乙酰氨基酚[acetaminophen]和抗组织胺预先给药。
（2）为静脉输注稀释和给药。不要静脉推注或丸注。
（3）对6个疗程推荐剂量(28天疗程)：
  1）在疗程1第1天100mg
  2）在疗程1第2天900mg
  3）在疗程1第8和15天1000mg
  4）在疗程2-6第1天1000mg
剂型和规格
1000 mg/40mL(25mg/mL)单次使用小瓶.
禁忌证
无。
警告和注意事项
（1）输注反应：患者用糖皮质激素，对乙酰氨基酚和抗组织胺预先给药。输注期间严密监视. 对反应中断或终止输注。
（2）肿瘤溶解综合征：预料肿瘤溶解综合征;用抗高尿酸血症药物预先给药和充分水化尤其是对有高肿瘤负荷和/或高循环淋巴细胞计数患者。纠正电解质异常，提供支持性医护和监视肾功能和液体平衡。
（3）中性粒细胞减少：对感染监视。
（4）血小板减少：监视血细胞计数和出血。出血的处理可能需要血液制品支持。
（5）免疫接种：不要给活病毒疫苗GAZYVA给予前或期间。
不良事件
最常见不良事件(发生率 ≥10%)是：输注反应，中性粒细胞减少，血小板减少，贫血，发热，咳嗽，和肌肉骨骼疾病。

FDA Approves Gazyva™ (Obinutuzumab) for People With Previously Untreated Chronic Lymphocytic Leukemia (CLL)
•Gazyva Demonstrated an 84 Percent Reduction in the Risk of Disease Worsening or Death When Combined with Chemotherapy Compared to Chemotherapy Alone
•Gazyva is the First Medicine Approved with the FDA’s Breakthrough Therapy Designation
Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that the U.S. Food and Drug Administration (FDA) approved Gazyva™ (obinutuzumab), also known as GA101, in combination with chlorambucil chemotherapy for the treatment of people with previously untreated chronic lymphocytic leukemia (CLL). Gazyva (pronounced gah ZY vuh) is the first medicine approved with the FDA’s Breakthrough Therapy Designation and the fifth cancer medicine from Genentech approved by the FDA in the past three years.
“Gazyva is an important new medicine for people with newly diagnosed chronic lymphocytic leukemia as it more than doubled the time people lived without their disease worsening compared to chlorambucil alone,” said Hal Barron, M.D., chief medical officer and head of Global Product Development. “We have spent 20 years researching blood cancer medicines, and we will continue to study Gazyva to assess its efficacy in other types of blood cancers.”
The FDA granted Gazyva Breakthrough Therapy Designation due to the significance of the positive progression-free survival (PFS) results from the Phase III CLL11 trial and the serious and life-threatening nature of CLL.
Today’s FDA approval is based on the outcomes of the CLL11 trial. The trial showed that people who received Gazyva in combination with chlorambucil chemotherapy had significantly reduced risk of disease progression or death (HR=0.16; p<0.0001) and lived significantly longer without their disease getting worse compared to those who received chlorambucil alone (median PFS 23.0 months vs. 11.1 months). The most common Grade 3/4 adverse events for those who received Gazyva in combination with chlorambucil compared to chlorambucil alone were infusion-related reactions during the first infusion (21 percent vs. 0 percent [chlorambucil is an oral medicine]), low platelet count (thrombocytopenia, 11 percent vs. 3 percent) and low count of certain types of white blood cells (neutropenia, 34 percent vs. 16 percent), though this did not result in an increased rate of infections in the Gazyva arm.
Final data from the CLL11 trial investigating the direct comparison between Gazyva in combination with chlorambucil and Rituxan® (rituximab) in combination with chlorambucil (Stage 2) will be presented at the American Society of Hematology’s (ASH) 55th Annual Meeting in December 2013.
Gazyva will be available to people in the United States within approximately two weeks. For those who qualify, Genentech plans to offer patient assistance programs for people taking Gazyva through Genentech Access Solutions. Doctors can contact Genentech Access Solutions at (888) 249-4918. More information is also available at http://www.Genentech-Access.com.
Marketing applications have also been submitted to other regulatory authorities, including the European Medicines Agency (EMA).
About Chronic Lymphocytic Leukemia (CLL)
CLL is one of the most common forms of blood cancer and in 2013, it is expected that there will be nearly 5,000 deaths from CLL in the United States. Most cases of CLL (95 percent) start in white blood cells called B-cells that have a protein called CD20 on their surface.
About Gazyva
Gazyva is a new monoclonal antibody designed to attach to CD20, a protein found only on B-cells. It attacks targeted cells both directly and together with the body's immune system.
Gazyva was discovered by Roche Glycart AG, a wholly owned, independent research unit of Roche. In the United States, Gazyva is part of a collaboration between Genentech and Biogen Idec.
Gazyva is now approved in combination with chlorambucil for people with previously untreated chronic lymphocytic leukemia (CLL) and is additionally being investigated in a large clinical program, including multiple head-to-head Phase III studies compared to Rituxan in indolent non-Hodgkin’s lymphoma (NHL) and diffuse large B-cell lymphoma (DLBCL).
Gazyva Efficacy In CLL
The pivotal Phase III CLL11 trial, conducted in cooperation with the German CLL Study Group (GCLLSG), is a multicenter, open-label, randomized three-arm study investigating the efficacy and safety profile of either Gazyva plus chlorambucil or Rituxan plus chlorambucil compared to chlorambucil alone in 781 previously untreated people with CLL and co-existing medical conditions.
The study showed that Gazyva demonstrated a statistically significant 84 percent reduction in the risk of disease worsening or death (PFS; HR=0.16, 95 percent CI 0.11-0.24, p<0.0001) when combined with chlorambucil compared to chlorambucil alone in people with previously untreated CLL and co-existing medical conditions. In the CLL11 study, no new safety signals were detected for Gazyva.
•Gazyva in combination with chlorambucil more than doubled the time people with newly diagnosed CLL lived without their disease getting worse (median PFS: 23.0 vs. 11.1 months).
•75.9 percent of people responded to Gazyva plus chlorambucil (overall response rate, or ORR) compared to 32.1 percent with chlorambucil alone.
•More than a quarter of the people who received Gazyva in combination with chlorambucil achieved a complete response (CR: 27.8 percent vs. 0.9 percent).
•The most common Grade 3/4 adverse events for those who received Gazyva in combination with chlorambucil compared to chlorambucil alone were infusion-related reactions during the first infusion (21 percent vs. 0 percent [chlorambucil is an oral medicine]), low platelet count (thrombocytopenia, 11 percent vs. 3 percent) and low count of certain types of white blood cells (neutropenia, 34 percent vs. 16 percent) though this did not result in an increased rate of infections in the Gazyva arm.
Gazyva Indication Statement
Gazyva™ (obinutuzumab) is a prescription medicine used with the chemotherapy chlorambucil, to treat chronic lymphocytic leukemia (CLL) in adults who have not had previous CLL treatment.
Important Safety Information
Patients must tell their doctor right away about any side effects they experience. Gazyva can cause side effects that can become serious or life-threatening including:
Hepatitis B Virus (HBV) Reactivation: may cause serious liver problems including liver failure and death. If patients have had hepatitis B or are carriers of HBV, receiving Gazyva could cause the virus to become an active infection again. Patients should not receive Gazyva if they have active HBV liver disease. A patient’s doctor will do blood tests to check for HBV infection prior to treatment and will monitor the patient during and for several months following their treatment.
Progressive Multifocal Leukoencephalopathy (PML): a serious brain infection that can lead to severe disability and death and for which there is no known prevention, treatment, or cure. Symptoms can include difficulty thinking, loss of balance, changes in speech or walking, weakness on one side of the body, or blurred or lost vision.
Additional possible serious side effects of Gazyva:
Patients must tell their doctor right away about any side effects they experience. Gazyva can cause side effects that may become severe or life-threatening, including:
•Infusion Reactions: may occur during or within 24 hours of the infusion. The patient’s doctor should give the patient medicines before their treatment that may help to reduce the risk of an infusion reaction. Symptoms can include hives, rash, itching, facial or oral swelling, sudden cough, shortness of breath, difficulty breathing, weakness, dizziness, feeling faint, racing heart, or chest pain.
•Tumor Lysis Syndrome (TLS): TLS is caused by a fast breakdown of cancer cells. TLS may cause an abnormal heartbeat or kidney failure requiring the need for dialysis treatment. The patient’s doctor may do blood tests to check the patient for TLS and give the patient medicines before their treatment to help prevent TLS. Symptoms of TLS may include nausea, vomiting, diarrhea and tiredness.
•Infections: Serious bacterial, fungal, and viral infections can occur during and following Gazyva therapy. Symptoms may include fever and cough.
•Low blood cell counts: The patient’s blood cell counts may be monitored during treatment.
Most common side effects of Gazyva
The most common side effects of Gazyva are infusion reactions, low white blood cell counts, low platelet counts, low red blood cell counts, fever, cough, muscle and joint pain.
Before receiving Gazyva, patients should talk to their doctor about:
Immunizations: Before receiving Gazyva therapy, patients must tell their healthcare provider if they have recently received or scheduled to receive a vaccine. People who are treated with Gazyva should not receive live vaccines.
Pregnancy: Patients must tell their doctor if patients are pregnant or planning to become pregnant, or are breastfeeding. It is not known if Gazyva may harm the patient’s unborn baby or pass into the patient’s breast milk. Women should use birth control while using Gazyva and for 12 months after treatment.
Patients must tell their doctor about any side effect that bothers them or that does not go away.
These are not all of the possible side effects of Gazyva. For more information, patients should ask their doctor or pharmacist.
Gazyva is available by prescription only.
Report side effects to the FDA at (800) FDA-1088 or