Toni Stephenson Lymphoma Center, the Hematologic Malignancies Research Institute, the Beckman Research Institute, of the City of Hope Cancer Center, Duarte, California.
College of Pharmacy, University of South Carolina, Columbia, South Carolina.
Oncologist. 2021 Aug;26(8):e1418-e1426. doi: 10.1002/onco.13713. Epub 2021 Mar 12.
Biosimilars are biologic drug products that are highly similar to reference products in analytic features, pharmacokinetics and pharmacodynamics, immunogenicity, safety, and efficacy. Biosimilar epoetin received Food and Drug Administration (FDA) approval in 2018. The manufacturer received an FDA nonapproval letter in 2017, despite receiving a favorable review by FDA's Oncologic Drugs Advisory Committee (ODAC) and an FDA nonapproval letter in 2015 for an earlier formulation. We discuss the 2018 FDA approval, the 2017 FDA ODAC Committee review, and the FDA complete response letters in 2015 and 2017; review concepts of litigation, naming, labeling, substitution, interchangeability, and pharmacovigilance; review European and U.S. oncology experiences with biosimilar epoetin; and review the safety of erythropoiesis-stimulating agents. In 2020, policy statements from AETNA, United Health Care, and Humana indicated that new epoetin oncology starts must be for biosimilar epoetin unless medical need for other epoetins is documented. Empirical studies report that as of 2012, reference epoetin use decreased from 40%-60% of all patients with cancer with chemotherapy-induced anemia to <5% of such patients because of safety concerns. Between 2018 and 2020, biosimilar epoetin use varied, increasing to 81% among one private insurer's patients covered by Medicare whose cancer care is administered with Oncology Analytics and to 41% with the same private insurer's patients with cancer covered by commercial health insurance and administered by the private insurer, to 0% in several Veterans Administration Hospitals, increasing to 100% in one large county hospital in California, and with yet-to-be-reported data from most oncology settings. We conclude that biosimilar epoetin appears to have overcome some barriers since 2015, although current uptake in the U.S. is variable. Pricing and safety considerations for all erythropoiesis-stimulating agents are primary determinants of biosimilar epoetin oncology uptake. IMPLICATIONS FOR PRACTICE: Few oncologists understand substitution and interchangeability of biosimilars with reference drugs. Epoetin biosimilar is new to the market, and physician and patient understanding is limited. The development of epoetin biosimilar is not familiar to oncologists.
生物类似药是高度类似于参比产品的生物药物，在分析特性、药代动力学和药效学、免疫原性、安全性和疗效方面具有高度相似性。生物类似的促红细胞生成素于 2018 年获得美国食品和药物管理局（FDA）批准。尽管 FDA 的肿瘤药物咨询委员会（ODAC）对其进行了有利的审查，并在 2015 年因早期配方收到了 FDA 的非批准信，但制造商在 2017 年仍收到了 FDA 的非批准信。我们讨论了 2018 年 FDA 的批准、2017 年 FDA ODAC 委员会的审查以及 2015 年和 2017 年的 FDA 完整回复信；审查了诉讼、命名、标签、替代、可互换性和药物警戒的概念；审查了欧洲和美国肿瘤学中生物类似的促红细胞生成素的经验；并审查了促红细胞生成素刺激剂的安全性。2020 年，AETNA、United Health Care 和 Humana 的政策声明表明，新的肿瘤学用促红细胞生成素必须是生物类似的促红细胞生成素，除非有其他促红细胞生成素的医学需求。实证研究报告称，截至 2012 年，由于安全性问题，接受化疗诱导性贫血的癌症患者中，参考用促红细胞生成素的使用从 40%至 60%降至<5%。在 2018 年至 2020 年期间，生物类似的促红细胞生成素的使用情况有所不同，在一家私人保险公司的 Medicare 覆盖患者中，接受 Oncology Analytics 管理的癌症治疗的患者中，其使用比例增加到 81%，而在同一私人保险公司的商业健康保险覆盖的癌症患者中，使用比例为 41%，在几个退伍军人管理局医院中，使用比例为 0%，在加利福尼亚州的一家大型县医院中增加到 100%，而在大多数肿瘤学环境中，尚未报告数据。我们的结论是，自 2015 年以来，生物类似的促红细胞生成素似乎已经克服了一些障碍，尽管目前在美国的使用率仍存在差异。所有促红细胞生成素刺激剂的定价和安全性考虑因素是生物类似的促红细胞生成素肿瘤学使用率的主要决定因素。对实践的意义：很少有肿瘤学家了解生物类似药与参比药物的替代和可互换性。促红细胞生成素生物类似药是市场上的新产品，医生和患者的理解有限。肿瘤学家对促红细胞生成素生物类似药的开发并不熟悉。
