Monoclonal Antibody and Fusion Protein Biosimilars Across Therapeutic Areas: A Systematic Review of Published Evidence

Abstract

BackgroundDespite regulatory efforts to formalize guidance policies on biosimilars, there remains a need to educate healthcare stakeholders on the acknowledged definition of biosimilarity and the data that underpin it.ObjectivesThe objectives of the study were to systematically collate published data for monoclonal antibodies and fusion protein biosimilars indicated for cancer, chronic inflammatory diseases, and other indications, and to explore differences in the type and weight (quantity and quality) of available evidence.MethodsMEDLINE, Embase, and ISI Web of Science were searched to September 2015. Conference proceedings (n = 17) were searched 2012 to July 2015. Included studies were categorized by originator, study type, and indication. To assess data strength and validity, risk of bias assessments were undertaken.ResultsAcross therapeutic areas, 43 named (marketed or proposed) biosimilars were identified for adalimumab, abciximab, bevacizumab, etanercept, infliximab, omalizumab, ranibizumab, rituximab, and trastuzumab originators. Infliximab CT-P13, SB2, and etanercept SB4 biosimilars have the greatest amount of published evidence of similarity with their originators, based on results of clinical studies involving larger numbers of patients or healthy subjects (N = 1405, 743, and 734, respectively). Published data were also retrieved for marketed intended copies of etanercept and rituximab.ConclusionsThis unbiased synthesis of the literature exposed significant differences in the extent of published evidence between molecules at preclinical, clinical, and post-marketing stages of development, providing clinicians and payers with a consolidated view of the available data and remaining gaps.Electronic supplementary materialThe online version of this article (doi:10.1007/s40259-016-0199-9) contains supplementary material, which is available to authorized users.

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

“…2,16,44,57 A 2016 systematic literature review found that most comparative studies reported for such intended copies were either analytical, non-clinical, or observational in nature; as such, there remains a significant dearth of published data demonstrating the safety and efficacy of these agents. 16 …”

“…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 …”

“…In recent years, biosimilar versions of complex fusion protein and monoclonal antibody (mAb) products have been authorized, and many others are in development. 16 The introduction of high-quality biosimilars has the potential to provide savings for healthcare systems and to expand access to biologics. 5–7 Indeed, greater treatment utilization and price reductions are already evident in areas where biosimilars have been introduced.…”