The European Medicines Agency announced on May 21 that it had extended the indication of the drug abatacept to include adults with rheumatoid arthritis who have failed to respond to one of several previous therapies, including methotrexate and/or a tumor necrosis factor inhibitor.

The extension of indication offers patients and clinicians more latitude in their treatment regimens. Previously, abatacept was approved only for patients who had failed to respond to both methotrexate and a tumor necrosis factor (TNF)–alpha inhibitor.

The agency also said that its Committee for Medicinal Products for Human Use had recommended a marketing authorization for leflunomide, a generic of Sanofi-Aventis’ Arava, for the treatment of active rheumatoid arthritis.

Abatacept (Orencia, Bristol-Myers Squibb) was first granted EU marketing authorization in 2007 for both adults with rheumatoid arthritis and for young people with a rare disease called polyarticular juvenile idiopathic arthritis who had failed to respond to therapy with at least one TNF-alpha inhibitor.

In April 2010, the EMA’s human medicines committee relaxed abatacept’s indication for juveniles to include use in patients who had failed to respond to “previous therapy with one or more disease-modifying anti-rheumatic drugs, including methotrexate or a TNF-alfa inhibitor.” The new adult indication follows accordingly.

The committee also recommended a marketing authorization for the steroid dexamethasone (Ozurdex, Allergan), in the form of a 700-mcg intravitreal implant, to treat macular edema following either branch retinal vein occlusion or central retinal vein occlusion in adults.

The implant, which is biodegradable, works by gradually releasing the steroid in the eye and prolonging its anti-inflammatory effect, the EMA said. Some known side effects of the implant are increased intraocular pressure and conjunctival hemorrhage, the agency said, and the human medicines committee requested that a pharmacovigilance plan be established for the product.

The human medicines committee expanded the therapeutic indication of one already authorized chemotherapy agent and restricted the indication of a hepatitis B drug, citing new concerns about resistance. Additionally, it determined that there was no need to restrict the use of two rotavirus vaccines over concerns about contamination with a porcine virus, and demanded a written plan from the beleaguered drug manufacturer Genzyme for cleaning up its act.

The EMA recommended that authorization of docetaxel (Taxotere, Aventis), be expanded to include adjuvant treatment, in combination with doxorubicin and cyclophosphamide, in patients with operable node-negative breast cancer. Patients must eligible to receive chemotherapy according to internationally established criteria for primary therapy of early breast cancer, the agency said.

It demanded that the product information of lamivudine, (Zeffix, Glaxo Group), be changed to restrict its therapeutic indication in chronic hepatitis B, citing high risk of resistance to the drug. “Treatment with lamivudine should only be initiated in patients with compensated liver disease when the use of an alternative antiviral agent with a higher genetic barrier to resistance is not available or appropriate,” the agency said. In patients with decompensated liver disease, it said, “lamivudine should always be used in combination with a second antiviral agent without cross-resistance to lamivudine.”

The committee further determined that the discovery of porcine circovirus (PCV) in some batches of the oral rotavirus live vaccines Rotarix (GlaxoSmithKline) and RotaTeq (Sanofi Pasteur), did not pose a risk to public health. Therefore, it said, use of the vaccines need not be restricted. However, the EMA said, “The CHMP is awaiting further information from the manufacturers on the root cause of the findings and on measures to manufacture the vaccines free of porcine circoviruses.”

Also on the quality-control front, the EMA reported that it heard a presentation last month by representatives of the U.S. pharmaceutical firm Genzyme, whose manufacturing problems, including a contamination threat, led to ongoing shortages of the drugs Cerezyme and Fabrazyme, with serious consequences for the patients dependent on them for treatment of rare, life-threatening diseases.

The agency reported that it had demanded that Genzyme carry out a risk assessment of its manufacturing processes and prepare a detailed plan for improvement that “should aim at proactive identification of potential risks and continuous assurance of quality and supply.” The EMA further demanded that Genzyme submit provide regular progress reports on the plan’s implementation.

Copyright (c) 2009 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

欧洲药品管理局(EMA)于5月21日宣布其已扩大阿巴西普类药物的适应证范围，以将其用于那些既往应用某种药物 [包括甲氨蝶呤和(或)肿瘤坏死因子(TNF)抑制剂]治疗无效的成年类风湿性关节炎患者。

 

该药适应证范围的扩大在治疗方案的选择方面为患者和临床医生提供了更大的自由度。之前，阿巴西普仅被批准用于治疗那些甲氨蝶呤和TNFα抑制剂治疗均无效的患者。

 

该机构还声称，其人用医疗产品委员会已建议将上市许可授予来氟米特(赛诺菲-安万特生产的Arava的通用名)，以治疗活动性类风湿性关节炎。

 

阿巴西普(Orencia，百时美施贵宝公司)首次获得欧盟(EU)的上市许可是在2007年，该许可限定其仅应用于治疗那些患有类风湿性关节炎的成年人及患有一种名为多关节型幼年特发性关节炎的罕见疾病、至少一种TNF-α抑制剂治疗无效的年轻人。

 

在2010年4月，EMA人用医疗产品委员会将阿巴西普的适应证范围从青少年放宽至可用于治疗那些“先前使用包括甲氨蝶呤或某种TNF-α抑制剂在内的一种或多种改善病情的抗风湿药”治疗无效的患者。成年患者的新适应证范围也据此进行了调整。

 

该委员会还建议将上市许可授予类固醇地塞米松(Ozurdex，Allergan公司)，将700μg该药植入患者玻璃体内可治疗成人视网膜分支静脉阻塞或视网膜中央静脉阻塞后发生的黄斑水肿。

 

EMA说，这种可进行生物降解的移植物会向眼内逐步释放出类固醇，从而延长了该药抗炎作用的持续时间。该移植物已知的副作用包括眼内压增高和结膜出血，该机构说，人用医疗产品委员会已要求为此类产品制定药物监视计划。

 

人用医疗产品委员会对一种已获上市批准的化学药物的治疗适应证进行了扩展，并对一种乙型肝炎类药物的适应证进行了限定，这引发了人们对药物耐受的新的关注。此外，针对公众对猪圆环病毒可能会污染轮状病毒疫苗的担忧，该机构还明确表示无须对这2种轮状病毒疫苗的使用进行限制，并要求因此事倍受批评的药物生产商健赞公司给出书面计划，以澄清其行为。

 

EMA建议扩大多西紫杉醇(Taxotere，安万特公司)的治疗许可范围，允许其与阿霉素和环磷酰胺联合使用，以对那些可接受手术的淋巴结阴性乳腺癌患者进行辅助治疗。患者在接受化疗前必需符合早期乳腺癌初始治疗相关的国际公认标准，该机构说。

 

该机构还要求更改拉米夫定(Zeffix，葛兰素集团)的相关产品信息，以限制该药在其治疗适应证慢性乙型肝炎中的应用，该药具有很高的耐药风险。“仅在那些耐药遗传阻力更大的备选抗病毒药物无法获得，或是不适用时，才应该开始使用拉米夫定治疗代偿性肝病患者，”该机构称。其同时认为，对那些失代偿性肝病患者而言，“始终应该将拉米夫定与另一种不具备对拉米夫定交叉耐药性的抗病毒药物联合使用。”

 

该委员会进一步确认说，在某些批次的轮状病毒口服活疫苗Rotarix(葛兰素史克)和RotaTeq(赛诺菲巴斯德)中所发现猪圆环病毒(PCV)不会对公众健康构成威胁。因此，该委员会认为无须限制该疫苗的使用。然而，EMA说：“人用医疗产品委员会(CHMP)正在等待来自制造商的进一步资料，其将就出现该结果的根本原因及生产不含猪圆环病毒的疫苗的相关措施进行说明。”

 

同样，在质量控制方面，EMA报告说其上月听取了美国健赞制药公司的代表发言，该公司在生产中所存在的问题(包括此次的污染威胁)已导致Cerezyme和Fabrazyme等药物出现持续短缺，对那些依赖此类药物治疗危及生命的罕见疾病的患者而言，这将造成严重后果。

 

该机构报告说，其已要求健赞公司对其制造工艺进行风险评估，并制定“以主动识别潜在风险并持续保证药品质量及供应为目标的”详细改进计划。EMA进一步要求健赞公司就该计划的执行情况定期提交进度报告。

 

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