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Biosimilars/Research

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Comparison of US and European biosimilar regulatory pathways

Biosimilars/Research | Posted 15/04/2011

The EU and the US have some differences in the way they approach biosimilars. Some of these differences were outlined in an article by Mr David Rosen and Mr Larry Lian published on 2 March 2011.

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Pharmacodynamic response of biosimilar filgrastim

Biosimilars/Research | Posted 22/04/2011

Research published online on 10 March 2011 on the pharmacodynamic response of recombinant human granulocyte colony-stimulating factor (G-CSF) filgrastim has shown that there is no difference between biosimilar and originator G-CSF.

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Biosimilar low molecular weight heparins in Brazil

Biosimilars/Research | Posted 15/04/2011

In Brazil, the registration of new drugs is carried out only when the regulatory agency (Agência Nacional de Vigilância Sanitária, Anvisa) is fully satisfied with their quality, efficacy and safety. Likewise for biosimilars it is necessary that the biosimilar be equally effective and safe and without contaminants in relation to the originator medicine.

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Ongoing monitoring of biosimilar G-CSF (filgrastim)

Biosimilars/Research | Posted 25/03/2011

Sandoz is carrying out ongoing studies to ensure the safety of its biosimilar recombinant human granulocyte colony-stimulating factor (filgrastim G-CSF). The MONITOR-GCSF study will recruit at least 1,000 patients from a minimum of 75 centres and follow them for a maximum of six cycles of chemotherapy.

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Biosimilar substitution in the EU

Biosimilars/Research | Posted 04/03/2011

Although many things—including regulations for licensing of biosimilars—are harmonised within the EU, the attitude towards biosimilars and their substitution within the different countries of the EU varies widely.

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The case for health economic studies on biopharmaceuticals

Biosimilars/Research | Posted 26/11/2010

In the not too distant future, patents will expire on some major biopharmaceuticals, such as interferons, insulins and granulocyte-colony stimulating factors [1]. This is likely to lead to the market entry of a number of biosimilars. A health economic approach to market access for biopharmaceuticals and biosimilars serves to aid researchers and decision makers in pharmaceutical companies and government to identify those products in the development process that are likely to be safe, effective and cost-effective. This approach should also guide the rationale for registration, pricing and reimbursement decisions.

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Biopharmaceuticals: the start of personalised medicine

Biosimilars/Research | Posted 26/11/2010

Biopharmaceuticals typically bind to their biological target, e.g. a protein linked to a disease [1]. Therefore, a biopharmaceutical is likely to be particularly efficacious in a specific subgroup of the patient population. For instance, trastuzumab is a monoclonal antibody that binds to the human epidermal growth factor receptor 2 (HER2) protein and has been shown to be efficacious in the treatment of patients with metastatic breast cancer whose tumours over-express HER2 [2]. This has implications for the clinical development of biopharmaceuticals in that it highlights the need to select the most responsive target population, to collect information on relevant patient characteristics, and to identify suitable biomarkers for responders [3]. It could be argued that, in this respect, biopharmaceuticals involve a paradigm shift towards personalised medicine.

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Health economic challenges for biosimilars

Biosimilars/Research | Posted 26/11/2010

Biopharmaceuticals represent a fast-growing segment of the pharmaceutical market, making up one third of products in the development pipeline and accounting for 9% of pharmaceutical expenditure [1]. Whereas the first generation of biopharmaceuticals tended to consist of first-in-class products addressing unmet clinical needs in small populations, e.g. bevacizumab for metastatic colorectal cancer, the current wave of products targets larger populations, e.g. insulins for type 2 diabetes mellitus [2].

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Market access for biopharmaceuticals and biosimilars: a case study

Biosimilars/Research | Posted 26/11/2010

Filgrastim is one of the first biopharmaceuticals for which biosimilars have entered the market. This case study illustrates the health economic challenges and the issues that arose in the R & D, registration, pricing and reimbursement of the biopharmaceutical and its biosimilars [1].

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Biosimilar EPOs show the same or better quality

Biosimilars/Research | Posted 12/11/2010

Researchers have found biosimilar erythropoietin (EPO) products have the same or even better quality compared with the original branded products.

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Epoetin alfa and pure red cell aplasia

Biosimilars/Research | Posted 01/10/2010

Most therapeutic proteins have the potential to induce an immune response. Cases of pure red cell aplasia (PRCA) were reported after the formulation of Eprex (epoetin alfa) was changed. It is now known that ‘the process is the product’ and the formulation cannot be changed without approval by the relevant authorities.

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Approval of biosimilar epoetins: how similar are they?

Biosimilars/Research | Posted 24/09/2010

A consensus has emerged that approval of biosimilars requires both biological and clinical evidence. The ‘comparability exercise’ requires consideration of a wide range of aspects, including analytical and physico-chemical characterisation by several methods, comparative biological assays, comparative immunogenicity assessment, among others. The use of different host cells for the biosimilar product and the comparator in principle is possible.

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Phase I trial of a biosimilar erythropoietin

Biosimilars/Research | Posted 25/08/2010

A Phase I clinical trial of Hospira’s biosimilar erythropoietin (EPO) in patients with anaemia associated with chronic renal failure and chemotherapy has started in the US.

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What clinical trials will be required for biosimilar mAbs?

Biosimilars/Research | Posted 25/08/2010

The relevant European guideline states that if the reference medicinal product has more than one indication, the efficacy and safety of a biosimilar has to be justified, if necessary by demonstrating it separately for each indication claimed. The guideline brings up the possibility of ‘extrapolating’ efficacy (granting several clinical indications that are licensed for the reference product, although only one of the indications has been studied in the clinical development programme of the biosimilar). This would not be done without serious consideration. The mechanism of action of monoclonal antibodies (mAbs) is usually complex and in many cases only partially understood.

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Technical challenges in defining mAbs

Biosimilars/Research | Posted 25/08/2010

Monoclonal antibodies (mAbs) are highly complex molecules with secondary and tertiary structures. The drug substance (the molecule itself) and drug product (the pharmaceutically formulated final product) are heterogeneous, i.e. a mixture of several slightly different structures. Although the molecular characterisation of a mAb molecule itself might have reached a high level of precision, reliability, quality and reproducibility, various possibilities for mAb heterogeneity exist. Variations to the mAb protein include alternative disulfide pairings/disulfide shuffling, deamidation, (methionine) oxidation, cyclisation of N-terminal glutamine residues and partial enzymatic cleavage during manufacturing. Variations of post-translational modifications such as glycosylation patterns include differential addition of sugars, alternative branching of sugar chains and others. Physicochemical characterisation of these characteristics currently remains cumbersome.

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How far does similarity go?

Biosimilars/Research | Posted 25/08/2010

How much similarity does a biosimilar monoclonal antibody (mAb) have to show to its reference mAb? The European overarching biosimilar guideline states that a biosimilar needs to be ‘similar, in molecular and biological terms, to the active substance of the reference medicinal product.’ The guideline gives an example to highlight this, stating that an interferon alfa-2b would not be acceptable as a reference product to a biosimilar interferon alfa-2a1. Because interferon alfa-2a and alfa-2b differ in only one amino acid, the guideline thus indicates that the entire amino acid sequence of the two molecules should be identical.

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The biosimilars challenge

Biosimilars/Research | Posted 30/07/2010

What are the challenges facing biosimilars? This was the question broached in a paper by Professor Håkan Mellstedt of the Department of Oncology, at the Karolinska University Hospital Solna, Stockholm, Sweden.

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Development of biosimilars mAbs

Biosimilars/Research | Posted 02/07/2010

Is the development of biosimilar monoclonal antibodies (mAbs) possible in Europe? This was the question broached in a paper by Dr Christian Schneider – Chairman of both the Committee for Advanced Therapies and Biosimilar Medicinal Products Working Party and Co-opted member of the Committee for Medicinal Products for Human Use.

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Challenges in the development of biosimilars mAbs

Biosimilars/Research | Posted 02/07/2010

What are the challenges facing development of biosimilar monoclonal antibodies (mAbs) in Europe? This was the question broached in a paper by Dr Christian Schneider – Chairman of both the Committee for Advanced Therapies and Biosimilar Medicinal Products Working Party and Co-opted member of the Committee for Medicinal Products for Human Use.

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Phase III study of a new biosimilar filgrastim product (Zarzio) published

Biosimilars/Research | Posted 04/06/2010

A biosimilar recombinant human granulocyte colony-stimulating factor (filgrastim) (rhG-CSF), Zarzio (Sandoz GmbH), was evaluated in healthy volunteers in four phase I studies and in neutropenic patients in a phase III study.