2013年11月13日，美国食品药品管理局(USFDA)已批准Ibrutinib(商标名 IMBRUVICA)作为套细胞淋巴癌的单个治疗药物，适用于之前用其他手段治疗过的套细胞淋巴癌患者，标志着该药物正式进入市场化运营阶段。
　　Ibrutinib 早先由Pharmacyclics公司单独开发。2011年，强生(JNJ)旗下子公司杨森制药(Jassen)通过先期支付1.5亿美元而获得与 Pharma -cyclics公司合作开发的权利。这款药物于今年2月份已被FDA授予突破性治疗药物资格。杨森制药于7月份向FDA提交了这款药物的上市申请，该药物用于治疗两种B细胞恶性肿瘤，即作为二线治疗药物用于慢性淋巴细胞性白血病(CLL)/小淋巴细胞淋巴瘤(SLL)和套细胞淋巴癌(MCL)治疗。10 月份，杨森制药再次宣布，已向欧洲药品管理局(EMA)提交了抗癌药物Ibrutinib的上市许可申请(MAA)，寻求批准用于上述三种血液性肿瘤的治疗。
　　此次Ibrutinib用于治疗套细胞淋巴癌获得批准是在对111名之前经历过治疗的患者进行全面试验的基础上做出的。药物效用结果显示，Ibrutinib在上述111名被试中的总体应答率高达65.8%，完全应答率达到17%，另有49%的患者为部分应答。持续应答时间的中值为 17.5个月。
　　美国每年大约有1.6万人被诊断为慢性淋巴细胞性白血病，目前该疾病的标准治疗通常是化疗。然而，好多慢性淋巴细胞性白血病老年患者无法容忍激进的治疗，而染色体17p缺失引起的恶性肿瘤患者通常对治疗没有响应。在临床试验中，Ibrutinib已证实有较高的总体响应和持续响应，不论染色体17p状态如何。因此，Ibrutinib的批准将为相关的患者带来福音。
　　早先有分析师已预测Ibrutinib所有适应症的年销售峰值将会达到大约5亿美元，其最大销售份额可能来自慢性淋巴细胞性白血病适应症，而目前该适应症正在进行三项期临床试验。Ibrutinib在治疗套细胞淋巴癌领域的首先批准相信会让处于III临床试验的其他几种适应症被批准的希望大增。
　　关于Ibrutinib
　　Ibrutinib 是一种名为Bruton’s酪氨酸激酶(BTK)抑制剂的首创新药。BTK是细胞生理活动中的一个重要蛋白，参与介导调控B细胞成熟和生存的胞内信号通路。在恶性B细胞中，B细胞受体信号通路过度活跃，该信号通路即包括BTK。Ibrutinib能够与BTK形成强有力的共价键，从而抑制恶性B细胞中过度活跃的细胞生存信号的传输，从而达到抑制肿瘤生长和转移的效果。

IMBRUVICA™
We are proud to introduce our first product, IMBRUVICA™. Please visit www.IMBRUVICA.com for more information.
INDICATION - IMBRUVICA™ is indicated for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. This indication is based on overall response rate. An improvement in survival or disease-related symptoms has not been established.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Hemorrhage – Five percent (5%) of patients with MCL had Grade 3 or higher bleeding events (subdural hematoma, gastrointestinal bleeding, and hematuria). Bleeding events including bruising of any grade occurred in 48% of patients with MCL treated with 560 mg daily. The mechanism for the bleeding events is not well understood. Consider the benefit-risk of ibrutinib in patients requiring antiplatelet or anticoagulant therapies and the benefit-risk of withholding ibrutinib for at least 3 to 7 days pre and post-surgery depending upon the type of surgery and the risk of bleeding.
Infections - Fatal and non-fatal infections have occurred. At least 25% of patients with MCL had infections ≥ Grade 3, according to NCI Common Terminology Criteria for Adverse Events (CTCAE). Monitor patients for fever and infections and evaluate promptly.
Myelosuppression - Treatment-emergent Grade 3 or 4 cytopenias were reported in 41% of patients. These included neutropenia (29%), thrombocytopenia (17%) and anemia (9%). Monitor complete blood counts monthly.
Renal Toxicity – Fatal and serious cases of renal failure have occurred. Treatment-emergent increases in creatinine levels up to 1.5 times the upper limit of normal occurred in 67% of patients and from 1.5 to 3 times the upper limit of normal in 9% of patients. Periodically monitor creatinine levels. Maintain hydration.
Second Primary Malignancies - Other malignancies (5%) have occurred in patients with MCL who have been treated with IMBRUVICA™, including skin cancers (4%), and other carcinomas (1%).
Embryo-Fetal Toxicity - Based on findings in animals, IMBRUVICA™ can cause fetal harm when administered to a pregnant woman. Advise women to avoid becoming pregnant while taking IMBRUVICA™. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.
Adverse Reactions - The most commonly occurring adverse reactions (≥ 20%) in the clinical trial were thrombocytopenia*, diarrhea (51%), neutropenia*, anemia*, fatigue (41%), musculoskeletal pain(37%), peripheral edema(35%), upper respiratory tract infection(34%), nausea (31%), bruising (30%), dyspnea (27%), constipation(25%), rash (25%), abdominal pain (24%), vomiting( 23%) and decreased appetite (21%).
Treatment-emergent decreases (all grades) of platelets (57%), neutrophils (47%) and hemoglobin (41%) were based on laboratory measurements and adverse reactions.
The most common Grade 3 or 4 non-hematological adverse reactions (≥ 5%) were: pneumonia (7%), abdominal pain (5%), atrial fibrillation, diarrhea (5%), fatigue (5%), and skin infections (5%). Treatment-emergent Grade 3 or 4 cytopenias were reported in 41% of patients. Ten patients (9%) discontinued treatment due to adverse reactions in the trial (N=111).
The most frequent adverse reaction leading to treatment discontinuation was subdural hematoma (1.8%). Adverse reactions leading to dose reduction occurred in 14% of patients.
Drug Interactions:
CYP3A Inhibitors - Avoid concomitant administration with strong or moderate inhibitors of CYP3A . If a moderate CYP3A inhibitor must be used, reduce the IMBRUVICA™ dose.
CYP3A Inducers - Avoid co-administration with strong CYP3A inducers.
Special Populations – Hepatic Impairment - Avoid use in patients with baseline hepatic impairment.
Report side effects to the FDA at +1-800-FDA-1088 or www.FDA.gov/medwatch.
Report side effects to Pharmacyclics at +1-877-877-3536, Option 3.