Imberti Davide, Marietta Marco, Polo Friz Hernan, Cimminiello Claudio
Haemostasis and Thrombosis Center, Internal Medicine Department, Piacenza Hospital, Via Taverna 49, Piacenza, Italy.
Department of Oncology and Hematology, Section of Hematology, University of Modena and Reggio Emilia, Modena, Italy.
Thromb J. 2017 May 10;15:13. doi: 10.1186/s12959-017-0136-2. eCollection 2017.
Recently, the European Medicines Agency (EMA) authorized the introduction and marketing of Thorinane® and Inhixa®, biosimilars of the Low Molecular Weight Heparin (LMWH) enoxaparin. The authorization path is considerably different from the guidelines published by the EMA in 2009, as well as from the recommendations from the International Society on Thrombosis and Haemostasis published in 2013. Indeed, both of them recommended that LMWHs biosimilars therapeutic equivalence should be demonstrated in at least one adequately designed clinical trial. Shortly after enoxaparin biosimilars approval, EMA published a revised version of its guideline, no longer requiring the execution of a clinical study in patients at risk of venous thromboembolism. Also the assessment of safety shows some relevant flaws, as it relies only on a 20 healthy volunteers study, clearly underpowered to draw any conclusions about the safety profile of the drug. In our opinion, the approach taken by EMA for approval of enoxaparin biosimilars raises serious concerns about their actual, clinical "similarity". On these grounds, with the endorsement of the Italian Society for Haemostasis and Thrombosis (SISET) and the Italian Society for Angiology and Vascular Medicine (SIAPAV), we elaborated the present document aimed at reviewing and reappraising some critical points regarding the introduction of biosimilars of LMWH in Europe. Moreover, we would strongly advise the Italian National Health Authorities not to entrust safety assessment to the post-marketing surveillance only, but to promote well designed and powered studies aimed at establish the actual efficacy and safety of LMWH biosimilars.
最近，欧洲药品管理局（EMA）批准了低分子量肝素（LMWH）依诺肝素的生物类似药Thorinane®和Inhixa®的引入和上市。其批准途径与EMA在2009年发布的指南以及国际血栓形成和止血协会在2013年发布的建议有很大不同。实际上，这两者都建议应在至少一项设计充分的临床试验中证明LMWH生物类似药的治疗等效性。依诺肝素生物类似药获批后不久，EMA发布了其指南的修订版，不再要求对有静脉血栓栓塞风险的患者进行临床研究。而且安全性评估也存在一些相关缺陷，因为它仅依赖于一项针对20名健康志愿者的研究，显然样本量不足以得出关于该药物安全性概况的任何结论。我们认为，EMA批准依诺肝素生物类似药所采用的方法引发了对其实际临床“相似性”的严重担忧。基于这些理由，在意大利止血与血栓形成协会（SISET）和意大利血管病与血管医学协会（SIAPAV）的支持下，我们精心撰写了本文件，旨在回顾和重新评估有关在欧洲引入LMWH生物类似药的一些关键点。此外，我们强烈建议意大利国家卫生当局不要仅将安全性评估委托给上市后监测，而是要推动设计良好且样本量充足的研究，以确定LMWH生物类似药的实际疗效和安全性。
