The evolving market of biosimilars

By our Editorial Team - 18/12/2017

Nicola Travierso, President of Velit Bio, discusses the market dynamics of, and opportunities in the future for, biosimilars in the US and Europe.

The current global biologics market is worth $127 billion ($60 billion in the US alone, and $35 billion in Europe), and it is growing at a rate of around 9% a year.

At the time of writing this article, 14 different biosimilars have been approved and registered in regulated markets across the world (Table 1). However, it is interesting to note that while the US shows the greater expenditure on biosimilars, this is based on a market of just five FDA-approved products (Celltrion’s infliximab-dyyb, Sandoz’s filigrastin-sndz and etanercept-szzs, Amgen’s adalimumab-atto, and Samsung Bioepsis’ infliximab-abda). Europe, on the other hand, has 24 approved individual products already, and the number is growing.

As with any pharmaceutical product, the development of a biosimilar needs to begin with non-clinical studies. For biosimilars, the purpose of non-clinical phase research – primarily pharmacodynamic and toxicological studies – is to detect differences between the biosimilar and the reference biologic product. Assuming that the biosimilar is shown to be ‘similar enough’ to the reference biological, R&D proceeds to the clinical phase, with the possibility to extrapolate findings from non-clinical, pharmacokinetic and pharmacodynamic studies, which allow for the conclusion of similar efficacy and safety.

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“These guidelines are implemented in the US, Europe and Japan,” explains Mr Travierso. “For each biosimilar under development the relevant regulatory agencies have an open discussion on whether more than one clinical trial is required, but typically no further clinical data are required if the pharmacokinetic and pharmacodynamic data allow for conclusions of efficacy and safety – and assuming the impurity profile and the nature of the product’s excipients do not give rise for concern.”

The lower costs associated with the development and approval of biosimilars is reflected in the lower prices for these products.

“Eating into a significant proportion of the biologic market in Europe is the practice of ‘switching’ biosimilars for more costly reference products,” says Dr Travierso.

In February 2014, France became the first EU country to allow substitution of biosimilars under certain conditions (only for naive patients). The Netherlands followed suit in March 2015, with the Dutch Medicines Evaluation Board (MEB) allowing substitution of biosimilars (this was a u-turn foor the MEB, which had previously stated in 2010 that patients should be kept on the same biological medicinal product if he was responding well).  In January 2016, Belgium allowed substitution of biosimilars, while in Italy a finance bill recently approved by the italian senate dictates that if one or more biosimilars enter the market, regional buying centers will have the opportunity to re-open the existing tender within the 60 days and this will lead to a more competitive tender process. Clearly, this type of legislation encourages the usage of biosimilars in European hospitals.
Meanwhile, in the US, in September 2014 the biosimilar substitution bill in interchangeable products was passed in eight states (Massachusetts, Florida, Virginia, Delaware, Indiana, Utah, North Dakota and Oregon). By January 2017, a total of 28 states, including Georgia and North Carolina, had passed biosimilar legislation.
The regulatory and economic climates in Europe, in particular, are driving an uptake of biosimilars in many countries. The UK’s National Health Service (NHS) has calculated a saving of $45 per day for the use of biosimilars (compared with a saving of $2 per day for the use of generic pharmaceuticals), demonstrating the significant savings that can be made with the use of these products.
This, in turn, opens market opportunities for companies developing and producing biosimilars. More than 30 biological products lost patent protection in 2015 and are now open for biosimilar development.
“Monoclonal antibody biologicals and second-generation biologicals will be the drivers,” declares Dr Travierso.
For example, he notes that, in the US, ten adalimumab, six rituximab, three infliximab and two etanercept biosimilars are under development for rheumatoid arthritis, ankylosing spondylitis, follicular lymphoma and/or psoriasis. Four bevacizumab biosimilars are in the pipeline for lung cancer, and four trastuzumab biosimilars are under development for breast cancer. Five pegfilgrastim biosimilars are in the pipeline for neutropenia, and two epoetin alfa biosimilars are under development for anaemia associated with chronic kidney failure. In addition, one cetuximab and two filgrastim biosimilars are under development. This is not an exhaustive list, but it goes some way to showing the growth of the biosimilar market, and what it might look like by 2020.
Naturally, as biosimilar companies thrive, reference products’ profit margins reduce. The danger is – as with any generics – that the incentive to innovate and create new biological products may one day fail to outweigh the associated risks and costs. And while biosimilars enable access to medicines that some patients might otherwise find themselves unable to afford, the existence of these biosimilars places pressure on the reference drug manufacturers to achieve returns on their investments before patents expire. This keeps the costs of new products high, and beyond the reach of many patients.
Until, of course, a biosimilar is made.
Nicola Travierso, President of Velit Bio, 1010 Wien – Wollzeile 1-3/3/3.2, Austria
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