Biosimilars have traditionally been seen by large pharmaceutical companies as a threat to their most profitable products and the priority objective has been to delay their arrival on the market as much as possible. Regulatory strategies that sought to literally shield the product (more than 100 patents protect Humira in the US), multiple disputes aimed at discouraging competitors, agreements (legal or not so much) with manufacturers to delay or control the entry of biosimilars, launch of improved formulations (the so-called "biobetter") but above all pressure on the doctor to create a reasonable doubt about its effectiveness "waiting for more data" and lobbying actions to prevent such data could be obtained, have been some of the tactics chosen to protect their products.
The success in the US, where the first biosimilar was approved in 2013, has been unquestionable, while in Europe things have been different. In the European model of universal coverage, the main payer is the Health Public Insurance System that receives funds from citizens via taxes. In order to prevent the system from collapsing, it is necessary that the increases in expenditure do not depart too much from those of GDP that are between 1 and 3% per year. Arrival of new biological treatments and the new combination therapies have been a great relief for patients with serious diseases, but at the same time represent a considerable increase in the pharmaceutical bill and the only solution to prevent this from collapsing is to release resources by getting important savings in after patent products. First were the promotion policies of generics and now is the time for biosimilars. After more than ten years in the market in Europe without incidents to mention, few doubt remain that they are safe and effective, so the approvals have multiplied on both sides of the Atlantic.
"In this context, pharmaceutical companies have had to accept the fact that biosimilars are here to stay. whether they like it or not."
In this context, pharmaceutical companies have had to accept the fact that biosimilars are here to stay. whether they like it or not. Strategic positioning has been very diverse: some companies such as Roche, AbbVie or GSK have decided to maintain their specialization in the development of innovators. They give up, at least for the moment, to enter this segment and prefer to concentrate their efforts on defending their brands.
Other companies such as Pfizer, Novartis or Amgen, have opted for a mixed strategy for the development of innovators and biosimilars. In the case of Novartis, through its subsidiary Sandoz and in the case of Pfizer through Hospira. Sanofi on the other hand and after the spin-off of Zentiva seems to have lost interest in this segment as well.
Big generic manufacturers are also represented, although with different levels of involvement and objectives. So far, Mylan, the aforementioned Sandoz, Teva or Fresenius have already approved biosimilars. Sandoz is currently the company with the largest and most diversified portfolio among the different biosimilar categories. Mylan intends to occupy a leading position in the market and, in addition to developing its own biosimilars, has reached different agreements with Momenta, Biocon, Lupin or Mabion to complete its portfolio. Current feeling is that the great generic market leader, Teva, had lagged a little behind in this segment, but its recent agreement with Celltrion seems to boost this giant again. Fresenius on the other hand maintains a more discreet participation, with two mAbs and a pegfilgrastim, although with several other products in the pipeline.
In the medium segment, Mundipharma has reached an agreement to distribute the biosimilars of the Korean company Celltrion in Germany, UK and Italy. Servier and Kern Pharma, well positioned "local champions" are the companies selected for the French and Spanish markets respectively. Another Korean company, Samsung Biotech, decided to partner with the biotech company Biogen to create a JV (Samsung Bioepis). The biosimilar portfolio is then being commercialized by Biogen in the different European markets and by MSD in the USA.
It remains to be seen what Indian companies are going to do with biosimilars, particularly Accord whose impact on the generic cancer market has been extraordinary and has already achieved rapid penetration of its first approved biosimilar in Europe, Accofil (filgrastim).
"The arrival of so many competitors with different business models means facing different strategies in an environment without clear rules and in continuous evolution"
The arrival of so many competitors with different business models means facing different strategies in an environment without clear rules and in continuous evolution. Although developing a biosimilar does not involve such a high investment as to put an innovative product on the market, the cost is far superior to developing a generic. To recover the investment, these companies must guarantee minimum margins and prevent these products from suffering the erosion of prices that has been seen in the case of generics, with discounts lately greater than 97% from innovative pre-patent expiration price. Optimization of the commercial strategy will therefore be a key factor.
In Europe so far the prescription by active ingredient for biological products is not allowed, so it seems necessary that the marketeer actively promote the product if it is expected that the doctor write the name on the prescription and ideally include the phrase "non-substitutable", a prerogative that still has. Maintaining a commercial structure of these characteristics is not cheap and if we finally end up talking about "biogenerics" instead of biosimilars, many companies that invested on this segment can be into difficulties.
We have seen in recent years how some companies register several brands of biosimilars of the same molecule, while others choose only one product. Although there are still few data available, we analyzed, based on the study carried out by the Emergpharma, the results in two products launched with a year of difference and following the two models. Next, we present the data, still very preliminary, as well as our comments.
In September 2013, the first infliximab biosimilar, developed by the Korean company Celltrion under the name CT-P13, was approved by the EMA. It was launched in the US Top 5 in early 2015. Celltrion registered two brands: Inflectra, whose rights Pfizer acquired, and Remsima, which would be marketed by Mundipharma in Italy, Germany and the UK, by Kern Pharma in Spain and by Servier in France.
Below you can see the evolution of sales of infliximab biosimilars and the original product in the 5 most important markets of the EU (DE, IT, FR, ES, UK) between 2016 and 2018.
As can be seen in the graph, just over two years after its launch, Inflectra-Remsima achieved market leadership.
In January 2016, Benepali, the first biosimilar of etanercept developed by Samsung Bioepis was approved. Samsung Bioepis is JV created between Samsung Biotech, a Korean company and Biogen, a biotechnology company of Danish origin. In the same quarter the first sales were registered in the German and other EU markets . Samsung chose to launch a single biosimilar through its partner Biogen, a company specialized in CNS and without previous experience in the world of biosimilars.
It is difficult to establish definitive conclusions about which strategy has been the most effective. If we place the two adoption curves and adjust the offset between both pitches, this is what we get:
It seems that the existence of two products would have provided a certain advantage, but in no case can we speak of an important difference. After two years in the market, the results practically overlap. We must take these data as not conclusive, anyway.
Whether or not it is more successful to multiply the products, the truth is that four companies have registered mAb biosimilars with more than one brand:
Celltrion has, in addition to the aforementioned inflectra-Remsima, four products with the same rituximab biosimilar: Truxima, Ritenvio, Blitzima and Rituzena.
Novartis (Sandoz) has registered two rituximab, Rixathon and Riximyo, and two adalimumabs: Hefiya and Hyrimoz.
Fresenius has registered two adalimumabs: Kromeya and Idacio.
Amgen two adalimumabs: Angevita and Solymbic.
It is not clear yet if all these products will finally see the light, given that some companies have expressed their fears of reaching an overcrowded market. In some cases, multibrands policy is linked to different approved indications, but considering what is really happening in the market, once the products are available, off-label use is expected to be a standard and therefore, launching multiple brands should be considered just a commercial strategy.
Data currently available does not allow us to affirm that a strategy with several brands (and different companies) is commercially more effective than marketing a single product. It is possible that having several products allows different pricing strategies to be established in the tenders, which could be a great competitive advantage in an “all or nothing” market. In certain cases (Germany), biosimilars manufactured by the same company under the same process are considered “bioidentical” and are substitutable at the pharmacy level, which could allow a company with two products in this category to combine two strategies, one with the prescriber and another in the pharmacy. There are many open options, but at the moment too many factors at play and few answers.