Risks associated with the decision to develop biosimilars
As we have seen in recent years, many companies that have developed or introduced biosimilars, with an eye on the main markets, that is, Europe and the US, have used the expected patent expiration date and the market size as the main and sometimes only criteria for selecting molecules. We know now that this analysis has not always been sufficient.
Firstly, the originators had perfectly designed the defense of their products that was organized on three pillars:
Permanent litigation, which especially in the US has meant delays of several years. Humira, for example, has registered more than 100 patents in this country alone
Line extensions and upgraded versions in order to “migrate” patients before the expiration of the patent. The development of intramuscular formulas in many products that were originally intravenous has been one of the most used formulas.
Changes in development and opacity in order to make difficult the comparison of biosimilars, something that is essential for their approval.
Moreover, companies like Abbvie resorted to having drastic price reductions to discourage the clinical development of more biosimilars using their molecules.
In addition to the strong defense of very well-positioned companies with almost unlimited resources, the analysis did not sufficiently consider the proliferation of medium-sized companies. These companies, which we will call Bioemergings, are in a perfect competitive position to use the development of these products as a springboard to enter the difficult and expensive world of R&D. They introduce a somewhat distorting effect on the market since their objectives are not always and/or not only economically oriented, meaning negative margins may be acceptable in the first steps of their business, which is not the case for the rest of the companies.
"The success achieved in the case of generics shows the way to a rapid reduction in prices: restriction of autonomy prescription, promotion of switching as soon as there are cheaper options, access to all companies that meet the criteria, and centralized tender models available with one or few winners"
Finally, the urgency and need for European governments to reduce pharmaceutical spending had not been taken enough into account. Needless to say, this has undoubtedly accentuated throughout the COVID-19 crisis. The success achieved in the case of generics shows the way to a rapid reduction in prices: restriction of autonomy prescription, promotion of switching as soon as there are cheaper options, access to all companies that meet the criteria, and centralized tender models available with one or few winners.
Although some of these lessons learned (shortages, quality problems) may enable the “winner takes all” models to soften, all the factors seem to lead us to expect that the cost reduction factor, as fast and as deep as possible, is going to be a fundamental and almost unique criterion in the most budget-impacting cases.
At this point, as indicated by Biopharmalinks consultancy in its report on the biosimilars market in Europe 2020, companies should recognize that the molecule selection process must take into account the new context, and understand how each part of the value process generation should affect the final decision in order to successfully play in this market.
Achieving a profitable strategy in this segment, as in any other, depends on being able to generate sales that compensate for the investment in product development and the costs inherent in its distribution and marketing. In this sense, biosimilars are different from both the innovative products under patent and the generics. Regarding the first, the big difference commercially is that the price can and will be an essential factor, so the companies should necessarily optimize the entire value chain, starting with the production model, continuing with the registration strategy, and paying special attention to marketing and distribution costs.
The main difference with generics is at the level of development and market costs. Compared to the 1-2 million dollars it costs to develop a generic, a biosimilar requires between 80-200 million. A generic company can afford a "big numbers" strategy to minimize risks. In addition, the incremental commercial costs are equally controlled if a correct portfolio strategy is applied, that is, introducing one more product hardly increases the overall commercial expenses. At the cost of developing a biosimilar, a company could develop up to 100 generic molecules. It is obvious that failing to select a biosimilar can be dramatic for the company, unless very high resources are available, which is possible to very few.
Once it is accepted that the selection of biosimilars in this second wave must take into account more factors to avoid past errors, we summarize below some “good practices” which we develop much more extensively in our report on the second wave of biosimilars:
It is important to select a molecule with the entire cycle in mind, not just market size and date of patent expiration.
It is due to identify and evaluate the impact of the protection policies that the innovators are putting or are going to put into practice and to what extent they can delay, hinder or prevent access to the market in time.
It is necessary to prioritize the cases in which it is possible to arrive first. Traditionally, the latter and later are barely eligible for 14-20% of the market
Attention should be paid to improvements in the manufacturing process so as not to become obsolete when launching or, in other words, identify the context at the time the product reaches the market, not the current one
Attention must also be paid to possible entry barriers for other competitors, especially at the technological level. A niche market with a limited number of competitors almost guarantees low levels of price erosion.
It should be assessed whether treatment paradigm changes are expected to affect market potential when the new product arrives to the market
We must minimize risks and costs in the regulatory strategy, especially those that could cause total failure, such as those situations in which there is a risk to life. To the extent possible, we should minimize phase III studies. Good & frequent communication with regulatory agencies can help a lot at this point.
It is necessary to identify and anticipate possible barriers to adoption, both by the doctor and the patient. The experience with insulins should serve as an example.
We have to consider and evaluate the impact of the tenders on the final sale price, knowing for example that, if the products enter the centralized purchasing system in southern European countries, the impact on prices will be very rapid and deep.
It should be mandatory to monitor the level of competition to be expected. From 7 competitors, the only real selection criterion will be the price
We must properly assess what the company's strategy will be in relation to biosimilars: class specialization (biological, biosimilars)? Therapeutic area strategy? A strategy focused on tenders? Global, regional, local?
Overall objectives pursued by the company and how the biosimilars fit on them should be defined in order to select the right ones and assess what kind of companies are developing potential competitors and which may be their strategy. Will the company be competitive in a 3-5 years scenario?
To carry out exhaustive monitoring of the process, establishing decision points to continue, modify, or abandon should be the standard.
In such a changing context, when the need to generate savings can easily become an emergency, especially if COVID treatments or vaccines are not as effective as thought, or if, as it seems, the use of biologics could have a positive effect on infected patients, driving to an increasing need of its use. The need to evaluate the impact of changes in decisions and having a strategy as flexible as possible will be key success factors. We now know that many of the more than 40 adalimumab biosimilars under clinical development will not come to the market. It is too high a cost that could certainly have been avoided with a more appropriate analysis of the circumstances. Now it's time to learn from past mistakes.
Biopharmalinks is an independent consultancy specialized in the strategic analysis of biosimilars. We have a database that incorporates profiles, including sales levels by country, of more than 70 biological drug molecules with an expired patent or expected to expire in the coming years. We also have a file of more than 260 companies that develop, manufacture, or market biosimilars worldwide. If you wish to receive more information about our services or reports, we are at your disposal.