Faccin Freddy, Tebbey Paul, Alexander Emily, Wang Xin, Cui Lu, Albuquerque Teotonio
a Biotherapeutics, Global Medical Affairs , AbbVie Inc ., San Juan , PR , USA.
b Gastroenterology & Biotherapeutics, US Medical Affairs , AbbVie Inc ., North Chicago , IL , USA.
Expert Opin Biol Ther. 2016 Dec;16(12):1445-1453. doi: 10.1080/14712598.2017.1238454. Epub 2016 Sep 27.
Loss of exclusivity for biological therapeutics opens the door for biosimilar development. Biosimilars must demonstrate structural, functional, and clinical similarity with a currently approved biological originator product. A therapeutic alternative for biologic-naive patients, a single switch from an originator to biosimilar has also been studied in clinically stable patients; further, switching therapy multiple times (alternating) between an originator and a biosimilar has been investigated. Because biosimilars are not identical to originators and no robust clinical data have convincingly demonstrated that switching or alternating therapy of stable patients is safe and efficacious, there is an imperative need to understand the characteristics of well-designed clinical trials to support these practices. Areas covered: Clinical trials of biosimilars are reviewed, with an emphasis on trial designs that incorporate therapy switching, including the NOR-SWITCH study as an example. Expert opinion: As currently designed, biosimilar clinical trials provide insufficient information to support switching or alternating between originator products and their biosimilars. Lack of regulatory guidance contributes to this void. More robust data are required to inform the safety and efficacy of switching or alternating therapies, particularly regarding immunogenicity risks. Studies that also include alternations of therapy are needed to address these knowledge gaps.
生物治疗药物独家经营权的丧失为生物类似药的开发打开了大门。生物类似药必须证明与目前已获批的生物原研产品在结构、功能和临床方面具有相似性。作为初治生物药患者的一种治疗选择，在临床稳定的患者中也研究了从原研药单次转换为生物类似药的情况；此外，还对在原研药和生物类似药之间多次（交替）转换治疗进行了研究。由于生物类似药与原研药并不完全相同，且尚无有力的临床数据令人信服地证明稳定患者的转换或交替治疗是安全有效的，因此迫切需要了解精心设计的临床试验的特点，以支持这些做法。涵盖领域：对生物类似药的临床试验进行了综述，重点是纳入治疗转换的试验设计，以NOR-SWITCH研究为例。专家意见：按照目前的设计，生物类似药临床试验提供的信息不足以支持在原研产品与其生物类似药之间进行转换或交替。缺乏监管指导导致了这一空白。需要更有力的数据来了解转换或交替治疗的安全性和有效性，特别是关于免疫原性风险。还需要开展包括治疗交替的研究来填补这些知识空白。
