The laboratory analysed the chemical structure, molecular weight distribution, in vitro anticoagulant activity and pharmcacological effects in animal models of thrombosis and bleeding.

Enoxaparin is a low molecular weight heparin (LMWH), it is used as an anticoagulant for the treatment and prevention of deep vein thrombosis, which can lead to blood clots in the lungs.

Heparins do not have a precise molecular weight due to the fact that they are heterogeneous mixtures of glycosamino-glycans. This makes it difficult to demonstrate similarity between different preparations of heparins.

Analysis of biosimilar heparins
Methods such as amino acid sequencing and use of physiochemical methods to determine the conformation and patterns of glycosylation for heparins, however, can relatively easily demonstrate similarity.

When 30 different batches of biosimilar products commercially available in Brazil were analysed compared to the originator (70 finished products) no significant differences were found, using proton magnetic resonance spectroscopy. Analysis of the molecular weight distribution of the oligosaccharides found in the biosimilar and originator enoxaparin also demonstrated the similarity.

Clinical trials
In Brazil, the discussion is focused on clinical trials rather than proving similarity based on physiochemical studies, in vitro tests and pharmacological assays.

However, at a symposium held in Boston, USA, in 2009 on the subject of biosimilar LMWHs, questions were raised over whether clinical trials involving 3,000−4,000 subjects may prove to be prohibitive for manufacturers of biosimilars. As the originator companies have an exclusivity period of 10 years within which time they can recoup their development costs, biosimilars manufacturers have no such luxury.

The authors believe that in order to move the debate on about the use of biosimilar LMWHs in Brazil, some proposals need to be made.

In order to reduce the burden on biosimilars manufacturers and yet still enable cheaper biosimilar drugs to enter the Brazilian market the authors make the following proposals [2], creating the opportunity of a closer association between researchers and regulatory agencies:

• to incorporate one monograph about LMWHs into the Brazilian Pharmacopeia to normalise the analyses of the batches and finished products containing enoxaparin
• to establish a protocol of pharmacological studies to be performed by the companies that commercialise biosimilar LMWHs
• to create a committee of experts with recognised experience in the area to assess the results of the analyses of the biosimilar versions of LMWHs available in Brazil, and to propose further studies.

Summary
The results of the study showed that the biosimilar preparations of enoxaparins available for clinical use in Brazil which were analysed are a valid therapeutic alternative to the originator drug. There is, however, need for appropriate guidelines for biosimilar LMWHs in Brazil to ensure compliance with regulatory requirements.

Conflict of Interest
This study was funded by Conselho Nacional de Política Energética (CNPe) and Filho de Amparo À Pesquisa do Estado do Rio de Janeiro (FAPERJ). The authors reported no potential conflict of interest relevant to their article [1].

Editor’s comment
Are clinical trials involving 3,000−4,000 subjects for the different diseases treatable by enoxaparin biosimilars feasible or indeed ethical in Brazil?

Please feel free to share your thoughts via email or in the comments section below. What are your views on biosimilars in Brazil? Should Brazil pursue clinical trials of this magnitude for biosimilars? Do you think that this will lead to a lack of biosimilars in Brazil?

Related articles

Amphastar’s biosimilar enoxaparin approved by FDA – Momenta launches lawsuit

Immunogenicity of biosimilar low molecular weight heparins

Biosimilar low molecular weight heparins in Brazil

Reference

1.  Mourão P, Glauser BF, Vairo BC, Pereira MS. Propositional debate on biosimilar enoxaparin in Brazil. Arq Bras Cardiol. 2012;98(1):e11-e14.