University of Luebeck, Institute of Physiology, Luebeck, Germany.
Expert Opin Biol Ther. 2012 May;12(5):581-92. doi: 10.1517/14712598.2012.672968. Epub 2012 Apr 3.
Recombinant human erythropoietin (rhEPO, epoetin) has prospered in the treatment of renal and chemotherapy-associated anemias. Since the patents of the original epoetins expired, biosimilars have been launched. Because these are not fully identical to the original products, non-clinical and clinical studies are necessary to show similarity with respect to quality, safety, and efficacy.
The article summarizes experiences with EU-approved biosimilar epoetins. In particular, the issue of immunogenicity is considered. Neutralizing anti-EPO antibodies can cause pure red cell aplasia (PRCA). Further, a first view is offered on future erythropoiesis-stimulating therapies.
The term "biosimilar" should only be used for follow-on biopharmaceuticals approved under a defined regulatory pathway. The primary rationale for the therapy with biosimilars is cost saving. Two biosimilar epoetins are available in the EU that are used at the same dose(s) and dosing regimen(s) for indications of the reference product. Their advent has stimulated innovator companies to develop second-generation products with improved pharmacokinetic properties. EPO-mimicking peptides are a new therapeutic option. Other strategies focus on orally active chemical drugs that induce endogenous EPO production ("HIF stabilizers"). Epo gene transfer is also possible, but needs to be further explored with respect to efficacy and safety.
重组人红细胞生成素（rhEPO，促红素）在治疗肾性和化疗相关性贫血方面取得了成功。由于原始促红素的专利已经过期，生物类似药已经问世。由于这些药物与原产品不完全相同，因此需要进行非临床和临床研究，以证明其在质量、安全性和疗效方面具有相似性。
本文总结了欧盟批准的生物类似促红素的经验。特别是考虑了免疫原性问题。中和性抗 EPO 抗体可引起纯红细胞再生障碍性贫血（PRCA）。此外，还对未来的促红细胞生成治疗进行了初步展望。
“生物类似药”一词仅应用于通过明确监管途径批准的后续生物制药。使用生物类似药的主要理由是节省成本。目前欧盟有两种生物类似促红素，其剂量和用药方案与参照产品相同，用于参照产品的适应证。它们的出现刺激了创新型公司开发具有改善药代动力学特性的第二代产品。EPO 模拟肽是一种新的治疗选择。其他策略侧重于具有口服活性的化学药物，这些药物可诱导内源性 EPO 产生（“HIF 稳定剂”）。EPO 基因转移也是可能的，但需要进一步研究其疗效和安全性。
