In 2012, worldwide sales for the top three selling tumour necrosis factor (TNF) inhibitors reached US$20 billion. These biological treatments for arthritis are costing patients between US$10,000–US$30,000 per year making the need for lower cost biosimilars clear [1].
There are currently no biosimilar monoclonal antibodies (mAbs) or soluble receptor constructs (cepts—large, intricate proteins with unique tertiary and quaternary structures that are inherently difficult to replicate) approved by EMA or FDA for treatment of rheumatic diseases, although randomized controlled trials are complete or ongoing, see Table 1 [1]. EMA is, however, reviewing two applications for marketing authorization of infliximab biosimilars, one of which is thought to come from South Korean biotechnology company Celltrion, which has already received approval for its product for rheumatoid arthritis and autoimmune diseases from the regulatory authorities in Korea [2].
Table 1: Biosimilars under development for treatment of rheumatic diseases
| Reference biological
|
Manufacturer
|
Prospective biosimilar
|
Stage of development
|
Indication
|
| Trials ongoing in highly regulated markets (defined by EMA and FDA)
|
| Adalimumab
|
Boehringer Ingelheim (Germany)
|
BI695501
|
Phase I completed
(New Zealand)
|
Healthy subjects
|
| Etanercept
|
Hanwha Chemical (South Korea)
|
HD203
|
Phase III (South Korea)
|
RA
|
| Etanercept
|
LG Life Sciences (South Korea)
|
LBEC0101
|
Phase I completed (South Korea)
|
Healthy subjects
|
| Etanercept
|
Mycenax Biotech (Taiwan)
|
TuNEX
|
Phase III (Japan and South Korea)
|
RA
|
| Infliximab
|
Celltrion
(South Korea)
|
CT-P13
|
Approved (South Korea)/ Phase 3 complete (EU) RA; AS/RA
Phase I complete (EU, South Korea)
|
AS
|
| Rituximab
|
Boehringer Ingelheim
|
BI 695500
|
Phase III (Argentina, EU, New Zealand, Norway, Peru, Ukraine, USA)
|
RA
|
| Rituximab
|
Celltrion
(South Korea)
|
CT-P10
|
Phase I (South Korea)
|
RA
|
| Rituximab
|
Merck
|
MK8808
|
Phase I (EU)
|
RA
|
| Rituximab
|
Pfizer (USA)
|
PF-05280586
|
Phase II (USA)
|
RA
|
| Rituximab
|
Samsung
|
SAIT 101
|
Trials halted
|
RA
|
| Rituximab
|
Sandoz Pharmaceuticals (Switzerland)
|
GP2013
|
Preclinical (ACR2012)
Phase II (EU, Argentina)
|
RA
|
| Rituximab
|
Teva Pharmaceutical Industries (Israel)
|
TL011
|
Phase II completed (EU) Phase III halted
|
RA
|
| Trials on-going in less regulated markets
|
| Rituximab
|
Boehringer Ingelheim
|
BI 695500
|
Phase III (Brazil, Guatemala, Russian Federation)
|
RA
|
| Rituximab
|
Merck
|
MK8808
|
Phase I (Belarus)
|
RA
|
| Rituximab
|
Sandoz Pharmaceuticals (Switzerland)
|
GP2013
|
Phase II (Brazil, India) RA
|
RA
|
| Preclinical
|
| Etanercept
|
Avesthagen (India)
|
Avent
|
Preclinical
|
|
| Etanercept
|
Protalix Biotherapeutics (Israel)
|
PRX-106
|
Preclinical
|
|
| RA: rheumatoid arthritis; AS: ankylosing spondylitis.
|
Legislation that regulates the manufacture, registration and approval of biosimilars varies considerably between different countries, and ‘copy biologicals’ approved in less highly regulated markets may not follow the same strict requirements as is required in Europe by EMA.
Biosimilars, as with all biologicals, are complex molecules to produce, and uncertainties surrounding the exact regulatory requirements have led some companies to suspend their development. This, however, has not put off others and, with patent expiries looming, rheumatologists should expect biosimilars to be with them very soon.
Conflict of interest
Most of the authors of the research article had received study support and/or consultancy fees from both generics and originator drug manufacturers. The research article was a result of the roundtable on ‘Biosimilars for the treatment of rheumatic diseases’, Berlin, Germany, 25 April 2012, which was made possible by an unrestricted educational grant from F. Hoffmann-La Roche. The sponsor had no involvement in the roundtable agenda or development of the manuscript.
Related articles
Biosimilars in rheumatology
EU guidelines for biosimilars
Challenges in the development of biosimilars mAbs
References
1. Dörner T, et al. The role of biosimilars in the treatment of rheumatic diseases. Ann Rheum Dis. 2013;72(3):322-8.
2. GaBI Online - Generics and Biosimilars Initiative. Biosimilar monoclonal antibody approved in Korea [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2012 May 3]. Available from: www.gabionline.net/Biosimilars/News/Biosimilar-monoclonal-antibody-approved-in-Korea
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