Noticia de Contratación

The available data on biosimilars in Europe are still insufficient to carry out a rigorous analysis to show correlations. However, given that the current moment is very important for companies that have to design and execute strategies in this segment, we must “work with what is there” and try to draw valid conclusions.

Following with our survey on biosimilars in EU markets, this time we have reviewed data on two anti-tnf alfa whose first biosimilars were approved in Europe in similar timelines: etanercept and infliximab (January 2016 Etanercept and May 2016 Infliximab).

The first thing to look at is the difference of biosimilar’s adoption the first year: 30% infliximab versus 4% etanercept. However, since then the trend is surprisingly parallel, reflecting an annual adoption increase of 20 points.

As showed in the table below, there are important differences between markets.

The UK is in all cases the country with higher biosimilars penetration, due to successful promotion policies implemented by NICE. Germany is the only country in which both molecules achieve a similar penetration. It would be necessary a further analysis to assess whether it is related to the role of parallel trade companies as "equalizers".It also surprises the great differences between molecules found in Italy, France and Spain, with oscillations of between 25 and 40 points, always in the sense of an earlier adoption of infliximab.

In order to determine possible reasons explaining the differences found between products of the same category, launched almost simultaneously, we have analyzed two points that we consider of the utmost importance: number of competitors available and competitive profiles of the companies marketing the products. Let's go a little more in depth.

Number of competitors

In 2016, two infliximab biosimilars were launched: Inflectra (Pfizer) and Remsima, (Mundipharma, Servier, Kern Pharma). In 2017, Flixabi (Biogen) followed and Zessly (Sandoz) at the end of 2018. On the other molecule, etanercept, Benepali (Biogen) was launched in 2016 and later in 2017 Erelzi (Sandoz).It is clear that there have always been more biosimilars of infliximab than etanercept and therefore more competition in market.

If we compare the adoption curves of biosimilars in both molecules, we see that they follow the same trend but with some relevant differences: the single etanercept's biosimilar launched in 2016, Benepali, gets just 4% MS the first year to reach 40% in 2018.

In the case of infliximab, each of the two biosimilars launched in 2016 achieves a similar MS in 2016 and 2017(15% the first year, an additional 10% the second). Looking at the data, it seems clear that the process of entry has been faster and deeper in infliximab than in etanercept.

It is also interesting to note that the adoption curve of the two biosimilars launched on 2016 follow the same trend the first two years until Inflexa (Pfizer) clearly takes the lead and is near to surpase originator Remicade (it already did during 2019)

Competitive profiles and strategies

The other element that could have the greatest relevance in the differences found is the competitive profile of the companies that have launched the products. They can be classified in two groups.

Large pharmaceutical companies marketing their own biosimilars.

Pfizer and Novartis are two examples. Both companies have made a clear committment to the generic and biosimilars segment. In the case of Pfizer, Hospira’s accquisition and the most recent agreement to purchase Mylan reflects company's interest in leading also this part of the business. In the case of Novartis, the activity in generics and biosimilars is mainly driven through Sandoz and Hexal since long time ago.

Regarding the molecules discussed here, Pfizer owns Embrel (innovator of etanercept) and also Inflexa (biosimilar of infliximab). Embrel still keeps more than half of the market, while Inflexa is close to becoming a sales leader among the different market infliximab. We can therefore consider that its commercial strategy has yielded good results.

Regarding Sandoz, we have little data at the moment for these molecules, since both biosimilars are among the last approved. In the case of Erelzi, market share in the second year was 8% in Germany, the first country where it was launched and the only one that can be realistically consider in this analysis.

Biosimilar developers launch through other companies.

Two Korean companies, Samsung Biologics and Celltrion have developed biosimilars from these two molecules. Samsung got the approval of Benepali (etanercept) by EMA in 2016 and Flixabi (infliximab) in 2017, while Celltrion managed to get Remsima (infliximab) approved also in 2016.

Samsung Biologics achieved a global agreement with Biogen for the launch of its biosimilar portfolio in Europe. The two companies created a JV (Samsung Bioepis) and Biogen took 49.9% of the shares. A new comer into the world of biosimilars, Biogen is a biotechnology company of Danish origin specializing in CNS drugs. Even today, these products represent more than 80% of total sales and it is not clear whether biosimilars are a strategic bet or an opportunistic decision. So far, results are dissimilar: in etanercept, Benepali managed to reach 40% of the market, although it should be noted that it was the first to launch with a wide margin on Erelzi. Flixabi, on the other hand, has barely managed to penetrate 5%, a very modest figure if we consider that infliximab biosimilars are already 63% of sales.

Celltrion choose to distribute the Market Authorization Holders (MA) to different partners. Mundipharma, an intermediate-sized company with great success in the sale of pain treatment products and facing patent expiration of its products, was the partner of choice in the fastest adoption markets (UK, Germany) and also in Italy. In addition to Remsima, Mundipharma also acquired the rights to Truxima, rituximab's first biosimilar. Results with Remsima were very positive in 2016 and 2017, reaching a 35% share, but in 2018 things were not so well, surpassed by Inflexa and losing 5% MS

In Spain, Remsima is marketed by Kern Pharma, a local generic company with experience in the hospital segment. Penetration grew from 10% in 2016 to 25% in 2018, however ten points below Inflectra's MS.

In France, Remsima was licensed to local leader Servier. Unlike Kern Pharma, Servier has experience in innovative products and also in some branded generics or generic +. In this case, the first year only achieved 5% of sales, coming to 25% in 2018. As in the case of Spain, MS is 10 points below Pfizer’s Inflectra.

Conclusions

Although few data are available, the following points seem clear and do not contradict common sense:

• In the case studied, two biosimilars launched at the same time managed to penetrate more and faster than just one

• Adding this case to the previous studies, it seems that according to data, after three years launch of the first biosimilar, innovator has lost at least half of the market.

• The “early biosimilars adopters” are: UK, Germany. Italy, France and particularly Spain follow at a much slower pace. This trend is quite consistent in the different molecules studied to date.

•It is not possible to say whether the companies that market globally biosimilars developed by themselves achieve better results than those that do so through third parties, since this would require an evaluation that exceeds the content of this article. However, in the case of infliximab, the strategy followed by Pfizer obtained better results in terms of sales than the one developed by Samsung in all markets.

• It is difficult to assess whether the results obtained by non-European biosimilar manufacturers can be considered as good. Getting 40% (Benepali), 25% (Remsima) or 5% (Flixabi) after less than three years may be sufficient ... or not, depending of the expectations and peers performance. Other considerations, mostly real profit, should help to determine the winners and losers on this game.

Three years or less is from all points of view an insufficient time frame to calibrate such a complex sector, but as we mentioned at the beginning of this post, we have to work with what there is because it is not possible to wait for more data to make strategic decisions.