Abstract

Healthcare systems worldwide are struggling to find ways to fund the cost of innovative treatments such as gene therapies, regenerative medicine, and monoclonal antibodies (mAbs). As the world’s best known mAbs are close to facing patent expirations, the biosimilars market is poised to grow with the hope of bringing prices down for cancer treatment and autoimmune disorders, however, this has yet to be realized. The development costs of biosimilars are significantly higher than their generic equivalents due to therapeutic equivalence trials and higher manufacturing costs. It is imperative that academics and relevant companies understand the costs and stages associated with biologics processing. This article brings these costs to the forefront with a focus on biosimilars being developed for Rheumatoid Arthritis (RA). mAbs have remarkably changed the treatment landscape, establishing their superior efficacy over traditional small chemicals. Five blockbuster TNFα mAbs, considered as first line biologics against RA, are either at the end of their patent life or have already expired and manufacturers are seeking to capture a significant portion of that market. Although in principle, market-share should be available, withstanding that the challenges regarding the compliance and regulations are being resolved, particularly with regards to variation in the glycosylation patterns and challenges associated with manufacturing. Glycan variants can significantly affect the quality attributes requiring characterization throughout production. Successful penetration of biologics can drive down prices and this will be a welcome change for patients and the healthcare providers. Herein we review the biologic TNFα inhibitors, which are on the market, in development, and the challenges being faced by biosimilar manufacturers.

摘要

世界各地的医疗保健系统都在努力寻找为基因疗法、再生医学和单克隆抗体 (mAb) 等创新疗法的成本提供资金的方法。由于世界上最著名的 mAb 即将面临专利到期，生物仿制药市场有望增长，希望降低癌症治疗和自身免疫性疾病的价格，然而，这尚未实现。由于治疗等效性试验和更高的制造成本，生物仿制药的开发成本明显高于其仿制药。学术界和相关公司必须了解与生物制剂加工相关的成本和阶段。本文将这些成本放在首位，重点介绍正在开发的类风湿性关节炎 (RA) 生物仿制药。mAb 显着改变了治疗前景，确立了其优于传统小化学品的功效。五款重磅炸弹 TNFα mAb 被认为是抗 RA 的一线生物制剂，要么专利期即将结束，要么已经到期，制造商正在寻求占领该市场的很大一部分。尽管原则上应该可以获得市场份额，尽管合规性和法规方面的挑战正在解决，特别是糖基化模式的变化和与制造相关的挑战。聚糖变体会显着影响需要在整个生产过程中进行表征的质量属性。生物制剂的成功渗透可以压低价格，这对患者和医疗保健提供者来说将是一个可喜的变化。在此，我们回顾了市场上正在开发的生物 TNFα 抑制剂，以及生物仿制药制造商面临的挑战。