Biosimilars for the Treatment of Cancer: A Systematic Review of Published Evidence

Abstract

BackgroundBiologic treatments for cancer continue to place a significant economic burden on healthcare stakeholders. Biosimilar therapies may help reduce this burden through cost savings, thereby increasing patient access.ObjectivesThe purpose of this study was to collate all published data to assess the weight of available evidence (quantity and quality) for proposed monoclonal antibody biosimilars and intended copies, for the treatment of cancer.MethodsMEDLINE®, Embase®, and ISI Web of Science® databases were searched to September 2015. Conference proceedings (17) were searched (2012 to July 2015). Searches of the United States National Library of Medicine ClinicalTrials.gov registry were also conducted. Risk of bias assessments were undertaken to assess data strength and validity.ResultsProposed biosimilars were identified in 23 studies (36 publications) in oncology and ten studies in 14 publications in oncology and chronic inflammatory diseases for bevacizumab, rituximab, and trastuzumab originators. Based on our review of the included published studies, and as inferred from the conclusions of study authors, the identified proposed biosimilars exhibit close similarity to their originators. Published data were also retrieved on intended copies of rituximab. It remains unclear what role these agents may have, as publications on rigorous clinical studies are lacking for these molecules.ConclusionWhile biosimilar products have the potential to improve patient access to important biologic therapies, robust evidence of outcomes for monoclonal antibody biosimilars in treating cancer patients, including data from comparative efficacy and safety trials, is not yet available in the published literature. Significant data gaps exist, particularly for intended copies, which reinforces the need to maintain a clear differentiation between these molecules and true biosimilars. As more biosimilars become available for use, it will be important for stakeholders to understand fully the robustness of overall evidence used to demonstrate biosimilarity and gain regulatory approval.Electronic supplementary materialThe online version of this article (doi:10.1007/s40259-016-0207-0) contains supplementary material, which is available to authorized users.

Biosimilars in oncology and inflammatory diseases: current and future considerations for clinicians in Latin America

“…These products (BCD-020, BEVZ92, and RTXM83) were considered “proposed biosimilars” in the aforementioned systematic literature review, and for each mAb there is evidence of one or more comparative clinical studies with the originator. 16,65 However, we have not identified detailed information in the public domain concerning the basis for regulatory approval in Latin America, and gaps have been highlighted in the published literature regarding these biologics. 16,65 Therefore, independent evaluation of these products is challenging.…”

“…16,65 However, we have not identified detailed information in the public domain concerning the basis for regulatory approval in Latin America, and gaps have been highlighted in the published literature regarding these biologics. 16,65 Therefore, independent evaluation of these products is challenging. For example, in 2014, the rituximab product RTXM83 (marketed as Novex® by Laboratorio Elea) was approved in Argentina seemingly before the primary completion of a comparative, non-inferiority, efficacy and safety trial with the originator product in diffuse large B-cell lymphoma (NCT02268045).…”

“…68 Additionally, published comparative analytical, non-clinical, and PK/safety data have been identified. 16,65 …”

“…69 We are unclear what supportive evidence was assessed by the Administración Nacional de Medicamentos, Alimentos y Tecnología Médica (ANMAT) when granting its approval. 70 No publications on BEVZ92 were identified in the above-mentioned systematic review 16,65 ; however, the results of a comparative PK trial in patients with metastatic colorectal cancer (NCT02069704) have been published subsequently in abstract form. 71 In 2017, the manufacturer of Bevax® registered a comparative PK study (NCT03293654) and a comparative efficacy and safety study (NCT03296163) for a potential bevacizumab biosimilar identified as MB02; we presume these trials are being conducted to support regulatory submissions in other localities.…”

“…46,50 The development program for BCD-020 encompassed comparative clinical studies in RA and lymphoma, from which data are available. 16,65,73 According to the manufacturer, multiple physicochemical and biological studies conducted in line with EMA guidelines have also been carried out, 72 although we are not aware that they have been published. 16,65 Prior to its approval in Latin America, BCD-020 was authorized in a number of other markets, including Russia (as AcellBia®), Kazakhstan, Sri Lanka, and Vietnam.…”