抗癌药Imbruvica(ibrutinib胶囊)获美国食品药品管理局（FDA)加速批准，用于既往接受过至少一次治疗的慢性淋巴细胞白血病（CLL）患者的治疗。 Imbruvica已于2013年11月获FDA批准，用于既往接受过至少一次来那度胺或其他药物治疗的套细胞淋巴瘤（MCL）患者的治疗，这2个适应症的获批，均基于整体缓解率（ORR）数据，该药对存活或疾病相关症状改善的数据尚未建立。 Imbruvica是首个每日一次、单一制剂、口服布鲁顿酪氨酸激酶（BTK）抑制剂，由强生和Pharmacyclics公司联合开发和商业化，此前Imbruvica治疗CLL和MCL适应症均已授予优先审查资格，并根据FDA的加速批准程序批准，同时Imbruvica也是FDA授予突破性疗法认定并获批的首批药物之一。 突破性疗法称号是2012年FDA安全和创新法案中制定的部分内容，目的是帮助加快用于严重致命疾病潜在新药的开发进度，这些药物的临床前研究就已显示比现有的治疗药物在一项或多项临床指标上具有明显改进。 慢性淋巴细胞白血病（Chronic Lymphocytic Leukemia，CLL）是一种淋巴细胞血液癌症，在美国，CLL是一种罕见病。据估计，每年有1.6万人确诊为CLL，有近4600人不幸死于CLL。 Imbruvica是布鲁顿酪氨酸激酶（BTK）抑制剂，通过阻断BTK抑制肿瘤细胞的复制和转移，从而起到抗癌作用。 商品名：Imbruvica 通用名：Ibrutinib 别名:PCI-32765,CRA-032765 中文名：依鲁替尼 中文化学名:1-[(3R)-3-[4-氨基-3-(4-苯氧基苯基)-1H-吡唑并[3,4-d]嘧啶-1-基]-1-哌啶基]-2-丙烯-1-酮 英文化学名：1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]prop-2-en-1-one 适应症：套细胞淋巴瘤，慢性淋巴细胞白血病 作用机理：不可逆布鲁顿酪氨酸激酶(BTK)抑制剂,与Btk活性位点半胱氨酸残基（Cys-481）选择性地共价结合,从而有效灭活BTK活性 药物分类：孤儿药，突破性药物 用法用量：每天口服1次(4粒140mg胶囊)共560mg 药物公司：Pharmacyclics, 强生 IMBRUVICA Rx Pharmacological Class: Bruton’s tyrosine kinase (BTK) inhibitor. Active Ingredient(s): Ibrutinib 140mg; caps. Company Pharmacyclics and Janssen Biotech Indication(s): Treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. Treatment of patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy. Both indications are based on overall response rate. An improvement in survival or disease-related symptoms has not been established. Pharmacology: Ibrutinib is a small-molecule inhibitor of BTK. Ibrutinib forms a covalent bond with a cysteine residue in the BTK active site, leading to inhibition of BTK enzymatic activity. BTK’s role in signaling through the B-cell surface receptors results in activation of pathways necessary for B-cell trafficking, chemotaxis, and adhesion. Nonclinical studies show that ibrutinib inhibits malignant B-cell proliferation and survival in vivo as well as cell migration and substrate adhesion in vitro. Clinical Trials: The safety and efficacy of Imbruvica in patients with MCL who have received at least one prior therapy were evaluated in an open-label, multi-center, single-arm trial of 111 previously treated patients. Imbruvica was administered orally at 560mg once daily until disease progression or unacceptable toxicity. Tumor response was assessed according to the revised International Working Group (IWG) for non-Hodgkin’s lymphoma (NHL) criteria. The primary endpoint in this study was investigator-assessed overall response rate (ORR). Based on investigator assessment, results showed an ORR of 65.8% (95% CI: 56.2%, 74.5%) with a complete response (CR) in 17.1% and a partial response (PR) in 48.6%. The median duration of response (DOR) was 17.5 months (95% CI: 15.8, not reached). An Independent Review Committee (IRC) performed independent reading and interpretation of imaging scans. The IRC review demonstrated an ORR of 69%. The median time to response was 1.9 months. The safety and efficacy of Imbruvica in patients with CLL who have received at least one prior therapy were evaluated in an open-label, multi-center trial of 48 previously treated patients. Imbruvica was administered orally at 420mg once daily until disease progression or unacceptable toxicity. The ORR and DOR were assessed using a modified version of the International Workshop on CLL criteria by an IRC. The ORR was 58.3% (95% CI: 43.2%, 72.4%), all partial responses. None of the patients achieved a complete response. The DOR ranged from 5.6 to 24.2+ months. The median DOR was not reached. Legal Classification: Rx Adults: Swallow whole with water. MCL: 560mg once daily. CLL: 420mg once daily. Concomitant moderate CYP3A inhibitors: 140mg once daily. Dose modifications for toxicities: see full labeling. Children: Not established. Warnings/Precautions: Risk of hemorrhage; consider the benefit/risk of withholding treatment for 3–7 days pre-and post-surgery. Monitor for fever and infections; evaluate promptly if occurs. Monitor for myelosuppression; obtain CBCs monthly. Risk of second primary malignancies (eg, skin cancer or other carcinomas). Hepatic or renal impairment. Monitor creatinine levels periodically. Maintain adequate hydration. Pregnancy (Category D); avoid. Nursing mothers: not recommended. Interaction(s) Concomitant strong CYP3A inhibitors taken chronically (eg, ritonavir, indinavir, nelfinavir, saquinavir, boceprevir, telaprevir, nefazodone): not recommended; for short-term (≤7days) use of strong CYP3A inhibitors (eg, ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin); consider interrupting ibrutinib therapy. If concomitant moderate CYP3A inhibitors must be used (eg, fluconazole, darunavir, erythromycin, diltiazem, atazanavir, aprepitant, amprenavir, fosamprevir, crizotinib, imatinib, verapamil, ciprofloxacin): reduce ibrutinib dose (see Adults). Avoid grapefruit and Seville oranges during treatment. Avoid concomitant strong CYP3A inducers (eg, carbamazepine, rifampin, phenytoin, St. John’s Wort); consider alternatives. Increased risk of hemorrhage with concomitant antiplatelets or anticoagulants. Adverse Reaction(s) Thrombocytopenia, diarrhea, neutropenia, anemia, fatigue, musculoskeletal pain, peripheral edema, upper respiratory tract infection, nausea, bruising, dyspnea, constipation, rash, abdominal pain, vomiting, decreased appetite, pyrexia, arthralgia, stomatitis, sinusitis, dizziness. How Supplied: Caps—90, 120 LAST UPDATED: 3/3/2014 美国FDA批准Imbruvica为罕见血癌 2013年11月13日美国食品药品监督管理局(FDA)批准Imbruvica(ibrutinib)治疗患者有套细胞淋巴瘤(MCL)，一种罕见和侵袭型血癌。 MCL是非霍奇金淋巴瘤一种罕见型式和在美国所有非霍奇金淋巴瘤病例6%。在MCL被诊断时，通常已播散至淋巴结，骨髓和其他器官。 Imbruvica是意向对已接受至少一种既往治疗有MCL患者。其作用通过抑制癌症繁殖和播散所需的酶。Imbruvica是第三被批准治疗MCL的药物。万珂[Velcade硼替佐米](2006)和雷利米得[Revlimid] (2013)也曾被批准治疗此疾病。 FDA的药物评价和研究中心血液学和肿瘤室主任Richard Pazdur，M.D.说：“Imbruvica的批准证明FDA为罕见疾病患者提供治疗的承诺，”“监管局与公司合作加快药物的发展，审查和批准，反映了对突破性治疗指定程序的承诺。” Imbruvica是接受FDA批准的第二个突破性治疗指定药物。2012年7月通过的食品和药品管理安全性和创新法，给予FDA能力在承办单位要求下如果初步的临床证据表明药物对严重或危及生命疾病患者超过可得到治疗实质性改进时FDA可能提供指定某个药物为突破性治疗。 在监管局加速批准程序下加速批准Imbruvica，该程序允许FDA根据临床资料显示药物对一个替代性终点合理地预测对患者临床获益影响时批准某个治疗严重疾病药物加速批准当公司进行确证性临床试验时提供患者更早得到有前途新药。FDA还授权Imbruvica优先审评和孤儿产品指定因为药物分别显示在治疗严重情况中安全性或有效性潜能和意向治疗罕见疾病。 Imbruvica对MCL的加速批准是根据一项研究其中111例参加者每天给予Imbruvica直至其疾病进展或副作用成为不能耐受。结果显示接近66%参加者治疗后其癌周数或消失(总体缓解率)。尚未确定对生存或疾病相关症状的改善。 在接受Imbruvica参加者中报道的最常见副作用是血小板减少，腹泻，中性粒细胞减少，贫血，疲乏，肌肉骨骼痛，水肿，上呼吸道感染，恶心，瘀伤，呼吸困难，便秘，皮疹，腹痛，呕吐，和食欲减低。其他临床上有意义副作用包括出血，感染，肾问题和其他类型癌症的发生。 The FDA has expanded the use of Imbruvica (ibrutinib; Pharmacyclics and Janssen Biotech) for patients with chronic lymphocytic leukemia (CLL) who have received at least one previous therapy. Imbruvica was approved in November 2013 for the treatment of mantle cell lymphoma (MCL) in patients who have received at least one prior therapy. Imbruvica is a small-molecule inhibitor of BTK that forms a covalent bond with a cysteine residue in the BTK active site, leading to inhibition of BTK enzymatic activity. Nonclinical studies have shown that ibrutinib inhibits malignant B-cell proliferation and survival in vivo as well as cell migration and substrate adhesion in vitro. The FDA's accelerated approval for CLL is based on a clinical study of 48 previously treated patients that received Imbruvica 420mg until they reached unacceptable toxicity or disease progression. Study results showed that 58% of patients had their cancer shrink after treatment (overall response rate). The duration of response also ranged from 5.6–24.2 months. However, an improvement in survival or disease-related symptoms has not been established. Imbruvica is available as 140mg capsules in 90- and 120-count bottles 美国FDA批准Imbruvica治疗慢性淋巴细胞性白血病 2014年2月12日美国食品药品监督管理局(FDA)扩展Imbruvica (ibrutinib)为曾接受至少一次既往治疗慢性淋巴细胞性白血病(CLL)患者的批准使用。. CLL是一种罕见血液和骨髓疾病通常随时间缓慢变坏，引起被称为B淋巴细胞，或B细胞的白细胞逐渐增加。美国国立癌症研究所估计在2013年15,680美国人被诊断和4,580死于此病。 Imbruvica通过阻断允许癌细胞生长和分裂酶起作用。在2013年11月，FDA授予Imbruvica 加速批准治疗有套细胞淋巴瘤患者，一种罕见和侵袭类型血癌，如那些患者既往接受至少一次治疗。 FDA的药物评价和研究中心血液学和肿瘤产品室主任Richard Pazdur，医学博士说“今天的批准为尽管正在进行以前治疗癌症已进展的CLL患者提供一种重要的新治疗选择，”“FDA 在监管局的加速批准过程下完成Imbruvica的新适应证审评，这在使最需要此药患者迅速得到这个新治疗中起至关重要的作用。” 在监管局的加速批准过程，FDA可根据一个替代指标或合理预测临床获益的中间终点批准一个药物。接受加速批准药物通常是受一项协议进行验证性临床试验和描述临床获益。Imbruvica 对CLL还接受优先审评和孤儿-产品指定因为药物证实有潜力分别是在某种严重情况治疗中显著改进安全性或有效性和意向治疗一种罕见疾病。 FDA的加速批准Imbruvica对CLL是根据一项48例既往治疗过参加者临床研究。本研究前参加者平均被诊断有CLL 6.7年和已接受既往四种治疗。所有研究参加者接受一个420 mg 口服给予剂量的Imbruvica直至治疗达到不可接受的毒性或疾病进展。结果显示接近58 %参加者治疗后有癌症皱缩(总体反应率)。在研究时间，反应时间范围从5.6至24.2个月。尚未确定生存或疾病相关症状的改善。 在临床研究中观察的最常见副作用包括血小板减少，腹泻，瘀伤，中性粒细胞减少，贫血，上呼吸道感染，疲乏，肌肉骨骼痛，皮疹，发热，便秘，周边水肿，关节痛，恶心，口腔炎，窦炎和眩晕。 Imbruvica是由Sunnyvale制造，总部设在加州Pharmacyclics公司。 ----------------------------------------------------- 注：以下产品不同规格和不同价格，购买以咨询为准！ -----------------------------------------------------     产地国家: 美国 原产地英文商品名: IMBRUVICA 140mgX90capsules 原产地英文药品名: ibrutinib 中文参考商品译名: IMBRUVICA 140毫克x90胶囊/瓶 中文参考药品译名: 依鲁替尼  拉铁尼伯 生产厂家中文参考译名: Pharmacyclics/Janssen Biotech Inc. 生产厂家英文名: Pharmacyclics/Janssen Biotech Inc. -----------------------------------------------------     产地国家: 美国 原产地英文商品名: IMBRUVICA 140mgX120capsules 原产地英文药品名: ibrutinib 中文参考商品译名: IMBRUVICA 140毫克x120胶囊/瓶 中文参考药品译名: 依鲁替尼  拉铁尼伯 生产厂家中文参考译名: Pharmacyclics/Janssen Biotech Inc. 生产厂家英文名: Pharmacyclics/Janssen Biotech Inc.