LYNPARZA 50MG CAPSULE (OLAPARIB) 112'S(OLAPARIB) 奥拉帕尼胶囊已获批上市
Pharmacological Class:
Poly (ADP-ribose) polymerase (PARP) inhibitor.

Active Ingredient(s):
Olaparib 50mg; capsules.

Company
AstraZeneca Pharmaceuticals

Indication(s):
Monotherapy in patients with deleterious or suspected deleterious germline BRCA-mutated (as detected by an FDA-approved test) advanced ovarian cancer who have been treated with ≥3 prior lines of chemotherapy.

Pharmacology:
Olaparib inhibits poly (ADP-ribose) polymerase (PARP) enzymes, including PARP1, PARP2, PARP3. It has been shown to inhibit growth of select tumor cell lines in vitro and decrease tumor growth in mouse xenograft models of human cancer both as monotherapy or following platinum-based chemotherapy.

In vitro studies have shown that olaparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complex, resulting in disruption of cellular homeostasis and cell death.

Clinical Trials:
The efficacy of Lynparza was eva luated in a single-arm study involving 137 patients with germline BRCA-mutated (gBRCAm) advanced cancers who had been treated with ≥3 prior lines of chemotherapy. All patients received Lynparza 400mg twice daily as monotherapy until disease progression or intolerable toxicity. The objective response rate (ORR) and duration of response (DOR) were assessed by the investigator.

Study results showed an ORR of 34% (95% CI: 26, 42) with a complete response in 2% of patients, and a partial response in 32% of patients. The median DOR was 7.9 months (95% CI: 5.6, 9.6).

Legal Classification:
Rx
Adults:
Swallow capsules whole. 400mg twice daily; max 800mg daily. Continue until disease progression or unacceptable toxicity. Dose adjustments for adverse reactions: reduce to 200mg twice daily; may further reduce to 100mg twice daily. If concomitant strong CYP3A inhibitor unavoidable: reduce to 150mg twice daily; or if concomitant moderate CYP3A inhibitor unavoidable: reduce to 200mg twice daily.

Children:
Not established.

Warnings/Precautions:
Monitor CBC at baseline and monthly thereafter; do not start therapy until recovery from hematological toxicity due to previous chemotherapy (CTCAE Grade ≤1). Discontinue if myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) is confirmed. Interrupt therapy and eva luate if new or worsening respiratory symptoms occur; discontinue if pneumonitis is confirmed. Hepatic and moderate-to-severe renal impairment: not studied. Pregnancy (Category D); avoid. Use effective contraception during therapy and for at least 1 month after last dose. Nursing mothers: not recommended.

Interaction(s)
Increased myelosuppressive toxicity with concomitant other myelosuppressive anticancer agents, including DNA damaging agents. Avoid concomitant strong CYP3A inhibitors (eg, itraconazole, telithromycin, clarithromycin, ketoconazole, voriconazole, nefazodone, posaconazole, ritonavir, lopinavir/ritonavir, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) and moderate CYP3A inhibitors (eg, amprenavir, aprepitant, atazanavir, ciprofloxacin, crizotinib, darunavir/ritonavir, diltiazem, erythromycin, fluconazole, fosamprenavir, imatinib, verapamil); if unavoidable, reduce dose (see Adults). Avoid grapefruit and Seville oranges. Avoid concomitant strong CYP3A inducers (eg, phenytoin, rifampicin, carbamazepine, St. John’s Wort) and moderate CYP3A inducers (eg, bosentan, efavirenz, etravirine, modafinil, nafcillin); if unavoidable, be aware of potential for decreased efficacy.

Adverse Reaction(s)
Anemia, nausea, fatigue, asthenia, vomiting, diarrhea, dysgeusia, dyspepsia, headache, decreased appetite, nasopharyngitis/pharyngitis/URI, cough, arthralgia/musculoskeletal pain, myalgia, back pain, dermatitis/rash, abdominal pain/discomfort; lab abnormalities (see full labeling), MDS/AML, pneumonitis.

How Supplied:
Caps—112

LAST UPDATED:
2/13/2015

FDA批准Lynparza(奥拉帕尼Olaparib)用于晚期卵巢癌
12月19日,美国FDA授予Lynparza（奥拉帕尼Olaparib）加速批准，这款新药用于治疗与BRCA基因缺陷相关的晚期卵巢癌妇女，该基因缺陷可通过一种FDA批准的诊断试剂进行检测。
卵巢癌形成于卵巢中，卵巢是女性生殖腺，共有一对，也是卵细胞（卵子）形成的地方。美国国家癌症研究所预测，2014年美国将有2.198万名妇女被确诊患有卵巢癌，有1.427万人会死于这种疾病。
Lynparza（奥拉帕尼Olaparib）是一种多聚二磷酸腺苷核糖聚合酶(PARP)抑制剂，它可阻断参与修复受损 DNA 的酶。这款药物适用于高度预处理的与BRCA基因缺陷相关的卵巢癌。
“今天的批准是一种用于治疗卵巢癌的新类型药物的首次批准，”FDA药物评价与研究中心血液及肿瘤产品办公室主任、医学博士Pazdur称。“Lynparza（奥拉帕尼Olaparib）被批准用于有特定BRCA基因缺陷的患者，这是对疾病潜在机理的一个更好理解，也是开发靶向、更具个体化治疗药物的一个例证。
FDA 批准Lynparza（奥拉帕尼Olaparib）时伴随批准一款叫BRACAnalysis CDx的基因检测试剂，它将用来检测卵巢癌患者的血样中是否存在BRCA基因突变(gBRCAm)。BRCA基因参与修复受损DNA，正常工作可抑制肿瘤增长。因突变而导致BRCA基因缺陷的妇女更可能发生卵巢癌，据预测，所有卵巢癌中10-15%的人与这些遗传性BRCA突变相关。
FDA通过该机构用于高风险医疗器械的上市前批准通道评价了BRACAnalysis CDx的安全性及有效性。目前为止，该生产商（一家临床实验室）一直在销售这种检测试剂，但不具体用作一种伴随诊断试剂，未获FDA批准作为一种实验室开发检测试剂 (LDT)，即一种被设计、生产及用于单一实验室的试剂。这款新的检测试剂被批准作为一种伴随诊断试剂，特别是用来识别可能成为Lynparza（奥拉帕尼Olaparib） 治疗候选人的晚期卵巢癌患者。
“安全有效伴随诊断试剂及药物的批准依然是肿瘤领域重要的发展，”FDA器械及放射卫生体外诊断及放射卫生办公室主任、哲学博士Gutierrez称。“我们很高兴BRACAnalysis CDx 成为FDA首款以及市前批准申请的方式而批准的一种LDT，也是一款首次获批的LDT伴随诊断试剂。伴随诊断试剂的使用有助于销售安全有效的特定满足患者需求的治疗药物。
FDA 对 BRACAnalysis CDx 的批准基于支持Lynparza（奥拉帕尼Olaparib）批准的临床研究数据。来自临床试验受试者的血样通过检测证实该试剂可用于检测这类人群的 BRCA 突变。
Lynparza（奥拉帕尼Olaparib）的疗效在一项由137名接受该药物治疗的 gBRCAm 相关卵巢癌受试者参与的研究中得到检测。这项研究旨在检测客观缓解率 (ORR)，亦即经历肿瘤部分缩小或完全消失的受试者的比例。结果显示，34% 的受试者经历了平均7.9个月的ORR。
Lynparza（奥拉帕尼Olaparib）的常见副作用有恶心、疲劳、呕吐、腹泻、扭曲的味道 (味觉障碍)、消化不良、头痛、食欲下降、常见的类似感冒症状(鼻咽炎)、咳嗽、关节疼痛(关节痛)、肌肉骨骼疼痛、肌肉疼痛(肌痛)、背部疼痛、皮疹(皮炎) 和腹痛。严重副作用包括发生骨髓增生异常综合征，这是一种骨髓不能产生足够功能性血细胞的病症，还包括急性骨髓性白血病（一种骨骨髓癌）及肺炎。
最常见的实验室异常情况有肌酐升高、平均红细胞容积增加、白细胞计数降低（淋巴细胞和中性粒细胞）及血小板水平降低。
6月份，Lynparza(奥拉帕尼Olaparib)作为维持治疗药物（阻止癌症回转的药物）的潜在立用途受到 FDA 肿瘤药物顾问委员会的审查。该委员会以11比 2的投票结果向FDA建议，数据不支持Lynparza（奥拉帕尼Olaparib）用于这一适应症的加速批准。在此会议之后，该公司提交了其它支持 Lynparza（奥拉帕尼Olaparib）用于不同用途的信息，即用于已接受三种或更多种化疗治疗的 gBRCAm 相关卵巢癌患者。
FDA 是以加速批准计划批准 Lynparza（奥拉帕尼Olaparib）,这一批准计划可允许基于显示一款药物对合理可能预测患者临床收益的代理终点有效的数据来批准这款药物用于治疗一种严重或危及生命的疾病。该计划可以使患者更早地获取新药，同时申请该药物的公司要进行验证性临床试验。
Lynparza（奥拉帕尼Olaparib） 的申请审评是在优先审评计划下完成的，这一计划为旨在治疗一种严重疾病或病症的药物提供一个加快的审评，如果获得批准，该药物与已上市产品相比将对疾病提供明显的改善。
BRACAnalysis CDx的上市申请是以FDA用于器械的优先审评计划而完成审评的，这一计划可为满足某种标准的器械提供优先审评，这包括旨在治疗或诊断一种危及生命或不可逆转的使人衰弱的疾病或病症，如果获得批准，该器械与已上市产品相比，将为疾病提供明显的、具有临床意义的优势
Lynparza（奥拉帕尼Olaparib）由位于特拉华州威尔明顿的阿斯利康上市销售。BRACAnalysis CDx位于盐湖城的 Myriad Genetic Laboratories 公司生产。