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


OBJECTIVE
The 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.


METHODS
MEDLINE, 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.


RESULTS
Across 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.


CONCLUSIONS
This 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.
Global Established Pharma Medicines Development Group, Pfizer Inc., 235 East 42nd Street, New York, NY, 10017-5755, USA. ira.jacobs@pfizer.com.
Ira
I
Jacobs
Global Established Pharma Medicines Development Group, Pfizer Inc., 235 East 42nd Street, New York, NY, 10017-5755, USA.
Danielle
D
Petersel
Outcomes and Evidence, Global Health and Value, Pfizer Inc., New York, NY, USA.
Lesley G
LG
Shane
Analytical Research and Development, Biotherapeutics Pharmaceutical Sciences, Pfizer Inc., Andover, MA, USA.
Chee-Keng
CK
Ng
Global Technology Services, Biotechnology and Aseptic Sciences, Pfizer Inc., Chesterfield, MO, USA.
Carol
C
Kirchhoff
Drug Safety Research and Development, Pfizer Inc., Groton, CT, USA.
Gregory
G
Finch
Envision Pharma Group, London, UK.
Sadiq
S
Lula
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D059451:Biosimilar Pharmaceuticals / Q000627:therapeutic use*; D002908:Chronic Disease; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D000069283:Rituximab / Q000627:therapeutic use; D012693:Serial Publications / Q000706:statistics & numerical data / Q000639:trends
D000911:Antibodies, Monoclonal; D059451:Biosimilar Pharmaceuticals; D011993:Recombinant Fusion Proteins; D000069283:Rituximab