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Cyramza(ramucirumab)获欧盟批准上市

2015-01-16 17:11:48 作者：新特药房来源：互联网浏览次数：134 文字大小：【大】【中】【小】

简介： ——欧盟首次批准专门用于胃癌二线的治疗2014年12月29日,礼来制药欧盟已批准 Ramucirumab (CYRAMZA®) 上市，联合紫杉醇用于治疗化疗经治的成人晚期胃癌或胃食管连接部（GEJ）腺癌以及作为单药用于不适 ...

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——欧盟首次批准专门用于胃癌二线的治疗
2014年12月29日，欧盟已批准 Ramucirumab (CYRAMZA®)上市，联合紫杉醇用于治疗化疗经治的成人晚期胃癌或胃食管连接部（GEJ）腺癌以及作为单药用于不适合联合紫杉醇的同类患者。这是 Ramucirumab 在欧盟获得的首次适应症注册批准。
今天标志着欧盟境内晚期胃癌治疗的一个重要里程碑，患者和医务人员现在拥有了一种批准专门用于这种难治性疾病二线治疗的药物，”礼来制药抗肿瘤事业部产品研发和医学事务高级副总裁 Richard Gaynor 博士表示：“我们很骄傲能兑现我们支持癌症患者及其医护人员这一承诺。”
此次欧盟上市批准是基于两项全球、随机、双盲、安慰剂对照III期研究的结果：RAINBOW 和 REGARD。RAINBOW 评估了 Ramucirumab 联合紫杉醇（一种化疗药物）用于化疗经治的晚期胃癌或 GEJ 腺癌，而 REGARD 则评估了 Ramucirumab 作为单药用于同样的患者。
欧洲药品管理局孤儿药品委员会（COMP）授予 Ramucirumab 为孤儿药，用于欧盟境内胃癌患者的治疗。孤儿药地位授予那些用于治疗罕见疾病，疗效显著好于现有治疗方法的药物。
关于 RAINBOW 试验
RAINBOW 是一项全球、随机、双盲、安慰剂对照III期研究，在含氟嘧啶和含铂初始化疗方案难治或上述方案使用后疾病进展的晚期（局部晚期、不可切除或转移性）胃癌（包括 GEJ 腺癌）患者中比较 Ramucirumab 联合紫杉醇和安慰剂联合紫杉醇。共有来自27个国家的665位患者进行了随机分组，RAINBOW 试验的主要疗效结果测量指标（即主要终点）为总生存期，支持性疗效结果测量指标（即次要终点）为无进展生存期。
关于 REGARD 试验
REGARD 是一项全球、随机、双盲、安慰剂对照III期研究，在含氟嘧啶和含铂初始化疗方案使用后疾病进展的局部晚期或转移性胃癌（包括 GEJ 腺癌）患者中比较 Ramucirumab 联合最佳支持治疗（BSC）和安慰剂联合 BSC。共有来自29个国家的355位患者进行了随机分组，REGARD 试验的主要疗效结果测量指标为总生存期，而支持性疗效结果测量指标为无进展生存期。
关于胃癌
胃癌在全球最常见的癌症中占第五位，同时也是全球第三大癌症相关死亡原因。2012年全球新发病例近一百万（631,000男性病例，320,000女性病例），约723,000死亡病例（469,000男性病例，254,000女性病例）。胃癌更常见于欧美以外的国家。欧洲胃癌罕见；据估计，2012年法国、德国、意大利、西班牙和英国新发胃癌总例数约为50,000。
胃癌是一种在胃部形成了癌细胞的疾病。这种疾病发展缓慢，通常需要很多年方可形成且经常不能检出。随着胃癌的进展，它能够随血流游走，扩散到诸如肝脏、肺和骨骼等器官。
最常见的胃癌类型是腺癌，它起源于胃粘膜中一种常见细胞。
关于 Ramucirumab
在欧盟，Ramucirumab (CYRAMZA®) 已经获得上市批准，与紫杉醇联合用于化疗经治成人晚期胃癌或胃食管连接部（GEJ）腺癌，并可作为单药用于不适合联合紫杉醇的同类患者。Ramucirumab在美国已获得批准用于化疗经治的晚期或转移性胃癌或 GEJ 腺癌患者。
Ramucirumab 是一种抗血管生成药物，在体内动物模型中可抑制血管生成。Ramucirumab 是一种 VEGF 受体2拮抗剂，通过特异性结合 VEGF 受体2，阻止 VEGF 受体配体 VEGF-A、VEGF-C 和 VEGF-D 的结合，来阻止 VEGF 受体2的激活。而 VEGF 介导的血管生成和多种疾病的发病机制相关，其中就包括了晚期胃癌。
目前正在进行或计划进行一些研究来探索 Ramucirumab 作为单药以及联合其它抗癌药物治疗多种肿瘤。
WARNING: CYRAMZA increased the risk of hemorrhage, including severe and sometimes fatal hemorrhagic events. Permanently discontinue CYRAMZA in patients who experience severe bleeding [see Dosage and Administration, Warnings and Precautions ].
DESCRIPTION
Description:
CYRAMZA (ramucirumab) is a recombinant human IgG1 monoclonal antibody that specifically binds to vascular endothelial growth factor receptor 2. CYRAMZA has an approximate molecular weight of 147 kDa. CYRAMZA is produced in genetically engineered mammalian NS0 cells.
CYRAMZA is a sterile, preservative-free, clear to slightly opalescent and colorless to slightly yellow solution for intravenous infusion following dilution and preparation. CYRAMZA is supplied at a concentration of 10 mg/mL in either 100 mg (10 mL) or 500 mg (50 mL) single-dose vials. CYRAMZA is formulated in glycine (9.98 mg/mL), histidine (0.65 mg/mL), histidine monohydrochloride (1.22 mg/mL), polysorbate 80 (0.1 mg/mL), sodium chloride (4.383 mg/mL), and Water for Injection, USP, pH 6.0.
CLINICAL PHARMACOLOGY:
Mechanism of Action:
Ramucirumab is a vascular endothelial growth factor receptor 2 (VEGFR2) antagonist that specifically binds VEGF Receptor 2 and blocks binding of VEGFR ligands, VEGF-A, VEGF-C, and VEGF-D. As a result, ramucirumab inhibits ligand-stimulated activation of VEGF Receptor 2, thereby inhibiting ligand-induced proliferation, and migration of human endothelial cells. Ramucirumab inhibited angiogenesis in an in vivo animal model.
INDICATIONS AND USAGE
INDICATIONS AND USAGE:
Gastric Cancer
CYRAMZATM as a single-agent is indicated for the treatment of patients with advanced or metastatic, gastric or gastro-esophageal junction adenocarcinoma with disease progression on or after prior fluoropyrimidine- or platinum-containing chemotherapy.
CONTRAINDICATIONS
Contraindications:
None
PRECAUTIONS
WARNINGS AND PRECAUTIONS:
1.Arterial Thromboembolic Events (ATEs): Serious, sometimes fatal ATEs have been reported in clinical trials. Discontinue CYRAMZA for severe ATEs.
2.Hypertension: Monitor blood pressure and treat hypertension. Temporarily suspend CYRAMZA for severe hypertension. Discontinue CYRAMZA for hypertension that cannot be medically controlled.
3.Infusion Related Reactions: Monitor for signs and symptoms during infusion.
4.Gastrointestinal perforation: Discontinue CYRAMZA.
5.Impaired Wound Healing: Withhold CYRAMZA prior to surgery.
6.Clinical Deterioration in Patients with Cirrhosis: New onset or worsening encephalopathy, ascites, or hepatorenal syndrome can occur in patients with Child-Pugh B or C cirrhosis.
7.Reversible Posterior Leukoencephalopathy Syndrome: Discontinue CYRAMZA.
ADVERSE REACTIONS
ADVERSE REACTIONS:
The most common adverse reactions observed in CYRAMZA-treated patients at a rate of 10% and 2% higher than placebo were hypertension and diarrhea.
To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
See PACKAGE INSERT for PATIENT COUNSELING INFORMATION and Medication Guide.
DOSAGE AND ADMINISTRATION
DOSAGE AND ADMINISTRATION:
Recommended Dose and Schedule
The recommended dose of CYRAMZA is 8 mg/kg every 2 weeks administered as an intravenous infusion over 60 minutes. Continue CYRAMZA until disease progression or unacceptable toxicity.
Do not administer CYRAMZA as an intravenous push or bolus.
Premedication:
Prior to each CYRAMZA infusion, premedicate all patients with an intravenous histamine H1 antagonist (e.g., diphenhydramine hydrochloride).
For patients who have experienced a Grade 1 or 2 infusion reaction, also premedicate with dexamethasone (or equivalent) and acetaminophen prior to each CYRAMZA infusion.
Dose Modifications:
Infusion Related Reactions (IRR)
Reduce the infusion rate of CYRAMZA by 50% for Grade 1 or 2 IRRs.
Permanently discontinue CYRAMZA for Grade 3 or 4 IRRs [see Dosage and Administration and Warnings and Precautions ].
Hypertension
Interrupt CYRAMZA for severe hypertension until controlled with medical management.
Permanently discontinue CYRAMZA for severe hypertension that cannot be controlled with antihypertensive therapy [see Warnings and Precautions].
Proteinuria
Interrupt CYRAMZA for urine protein levels 2 g/24 hours. Reinitiate treatment at a reduced dose of 6 mg/kg every 2 weeks once the urine protein level returns to <2 g/24 hours. If the protein level 2 g/24 hours reoccurs, interrupt CYRAMZA and reduce the dose to 5 mg/kg every 2 weeks once the urine protein level returns to <2 g/24 hours.
Permanently discontinue CYRAMZA for urine protein level >3 g/24 hours or in the setting of nephrotic syndrome [see Adverse Reactions].
Wound Healing Complications
Interrupt CYRAMZA prior to scheduled surgery until the wound is fully healed [see Warnings and Precautions].
Arterial Thromboembolic Events, Gastrointestinal Perforation, or Grade 3 or 4 Bleeding
Permanently discontinue CYRAMZA [see Warnings and Precautions]
Preparation for Administration
Inspect vial contents for particulate matter and discoloration prior to dilution [see Description]. Discard the vial, if particulate matter or discolorations are identified. Store vials in a refrigerator at 2°C to 8°C (36°F to 46°F) until time of use. Keep the vial in the outer carton in order to protect from light.
•Calculate the dose and the required volume of CYRAMZA needed to prepare the infusion solution. Vials contain either 100 mg/10 mL or 500 mg/50 mL at a concentration of 10 mg/mL solution of CYRAMZA.
•Withdraw the required volume of CYRAMZA and further dilute with only 0.9% Sodium Chloride Injection in an intravenous infusion container to a final volume of 250 mL. Do not use dextrose containing solutions.
•Gently invert the container to ensure adequate mixing.
•DO NOT FREEZE OR SHAKE the infusion solution. DO NOT dilute with other solutions or co-infuse with other electrolytes or medications.
•Store diluted infusion for no more than 24 hours at 2°C to 8°C (36°F to 46°F) or 4 hours at room temperature (below 25°C [77°F]).
•Discard vial with any unused portion of CYRAMZA.
Administration
Visually inspect the diluted solution for particulate matter and discoloration prior to administration. If particulate matter or discolorations are identified, discard the solution.
Administer diluted CYRAMZA infusion via infusion pump over 60 minutes through a separate infusion line. Use of a protein sparing 0.22 micron filter is recommended. Flush the line with sterile sodium chloride (0.9%) solution for injection at the end of the infusion.
HOW SUPPLIED
DOSAGE FORMS AND STRENGTHS:
100 mg/10 mL (10 mg per mL) solution, single-dose vial
500 mg/50 mL (10 mg per mL) solution, single-dose vial
Storage and Handling
Store vials in a refrigerator at 2°C to 8°C (36°F to 46°F) until time of use. Keep the vial in the outer carton in order to protect from light. DO NOT FREEZE OR SHAKE the vial.
For product diluted in 0.9% sodium chloride, the chemical and physical stability have been demonstrated for up to 24 hours at 2°C to 8°C (36°F to 46°F) or for 4 hours at room temperature (below 25°C [77°F]). DO NOT FREEZE OR SHAKE the diluted product