András Inotai (Semmelweis University and Syreon Research Institute; both Budapest, Hungary) discusses his presentation from ISPOR Europe 2019 (2—6 November; Copenhagen, Denmark) on the opportunities that biosimilars offer to improve patient access in countries with restricted healthcare resources.
In this feature, we take a ‘look behind the lecture’ with AndrÃ¡s Inotai (Semmelweis University and Syreon Research Institute; both Budapest, Hungary) as he discusses his presentation from ISPOR Europe 2019 (2—6 November; Copenhagen, Denmark) on the opportunities that biosimilars offer to improve patient access in countries with restricted healthcare resources.
Please could you introduce yourself?
I am an Associate Professor in the Center for Health Technology Assessment at Semmelweis University, as well as the Head of pharmaceutical policy research at Syreon Research Institute.
What are the potential benefits and challenges associated with biosimilars
Commonly, stakeholders adopt one of two perspectives on biosimilars. The first, more well-known, approach is that they can generate healthcare savings through market competition — the ‘disinvestment scenario’. This is a valid value proposition in countries where an original biological product, prior to its patent expiry, was available for all eligible patients. Indeed, this is the case in certain higher-income countries, for example some in Western Europe, in which there exist very limited, or no, economic constraints.
On the other hand, there are countries in which there are some, or more severe, economic constraints; in these countries, original biological medicines are often on the list of reimbursed pharmaceuticals but are not necessarily available for all eligible patients. In these countries, off-patent biologicals — off-patent originators and biosimilars — can create opportunities, due to their more affordable pricings, to treat additional patients and thus, at least partly, alleviate some of the negative effects of access restrictions.
Finally, there are those countries in which very severe economic constraints exist, for example some eastern European countries that are not members of the European Union. In these countries, original biologicals are often not even cost effective themselves prior to their patent expiry. After patent expiry of original products, when price erosion occurs due to competition, off-patent products can create opportunities for patients to have access to new, active biological compounds for the first time. Therefore, it is ultimately inappropriate to consider off-patent pharmaceuticals, including biologicals, only from a cost savings perspective because, in countries with economic constraints, they can create opportunities to invest in health and increase the number of treated patients — i.e., the investment scenario .
In countries with severe economic and budgetary restraints, can the same cost—effectiveness and value models be applied?
This is a very valid question: if we approach biosimilars that have already been approved by, for example, the EMA in the EU, from the perspective that they can save money (i.e. the disinvestment case), then we can apply very simple cost-minimization analyses. In these situations, it is very clear: original biological products’ patents expire, competition facilitates price erosion and more affordable treatments, delivering the same health gains, are made available.
However, in countries with severe economic constraints, where original biological medicines are not always on the list of medicines available with reimbursement, one cannot use such cost-minimization analyses, as the original biological product cannot act as a policy-relevant (i.e. reimbursed) comparator.
…it is ultimately inappropriate to consider off-patent pharmaceuticals, including biologicals, only from a cost savings perspective because, in countries with economic constraints, they can create opportunities to invest in health and increase the number of treated patients…”
Instead, we must use standard, previous-line, small-molecule medicines, available with reimbursement, as policy-relevant comparators. Compared with these medicines, new biosimilars often provide health gains, but at additional costs. In these cases, there is a potential need to employ economic models as well; one cannot simply use cost-minimization analyses.
Additionally, there is a lot of discussion currently surrounding value assessment techniques for off-patent biologicals and biosimilars. For example, the Biosimilar Special Interest Group recently formulated by ISPOR, in which I am involved, has multiple objectives. One objective is to provide solid scientific evidence on the value assessment of biosimilars in different scenarios and settings.
What was the driving force behind setting up the Biosimilars Special Interest Group?
I think a big driving force behind setting up the Special Interest Group was simply that biosimilars are a really hot topic; recently, certain monoclonal antibodies, as active compounds, have been losing their patents and many additional blockbuster biological medicines are about to lose their patents in the near future. There is, understandably, great pressure on pharmaceutical budgets and many of us think that more affordable, off-patent biologicals, delivering the same health gains, have the potential to be part of the solution to this strong budget pressure.
A second factor that I believe has been important in driving the setup of this Special Interest Group concerns the fact that, recently, much more evidence relating to biosimilars has been accumulated and published. Ten years ago, it was very easy to claim that ‘one should be careful of biosimilars because they may trigger adverse immunologic reactions’. However, currently available real-world evidence suggests that these concerns appear to be based on mainly anecdotal evidence; evidence available on EMA- and US FDA-approved biosimilars seems not to support this negative theory.
There is, understandably, great pressure on pharmaceutical budgets and many of us think that more affordable, off-patent biologicals, delivering the same health gains, have the potential to be part of the solution to this strong budget pressure.”
Many nordic European countries, which pioneered biosimilar track policies, have now accumulated much real-world evidence on the consequences of switching from originator biologicals to biosimilars with the same active compounds. Interestingly, even in some western European countries where one may assume that there are no severe access problems, after originator biological medicines’ patents expire we have observed increases in utilization , which confirm again that when off-patent pharmaceuticals are available, we may be able to treat a greater number of patients with more affordable medicines, or treat patients at earlier, less severe disease stages. It is noteworthy that biologicals are of relatively high price; if more affordable treatment options become available, then these high-cost medicines may be available for those patients who could not be treated previously because of existing budget restrictions.
What have you done so far in the year since the Biosimilars Special Interest Group was founded? What are your aims for the coming year?
So far, two significant Special Interest Group events have been held during ISPOR conferences: one during the ISPOR Annual Conference (18–22 May 2019; New Orleans, LA, USA) and one at the ISPOR Europe Conference (2—6 November 2019; Copenhagen, Denmark). We have presented two workshops/forums at these events, which have been well received and attended. Particularly, at the ISPOR Europe event, the Central and Eastern Europe (CEE) consortium of ISPOR was also involved and, as discussed, countries in CEE with some economic constraints can be among the most important beneficiaries of biosimilars. There was also a strong biosimilars industry presence at the session, as well as several originator biological manufacturing companies: we really had a multi-stakeholder audience.
…at international launch price levels, in [Central and Eastern Europe], new pharmaceutical products are often not cost effective.”
The Special Interest Group consists two main working groups; one is a member engagement group, working on webinars and education materials about biosimilars. The second is a scientific working group, which is working on the key project concerning biosimilars’ value-assessment. This project is to be based on solid scientific evidence; it is going to be a large systematic literature review, the completion timeline for which is approximately 2—4 years.
What factors are important to consider when modelling the cost—effectiveness of treatments?
It is essential to adopt health economic models, which are used locally in countries in CEE. These models must be adopted in terms of cost vectors and local epidemiological data. From my perspective as a researcher, this is challenging because, at international launch price levels, in CEE, new pharmaceutical products are often not cost effective. This is partly because the cost-savings potential of patent-protected pharmaceuticals (i.e. in terms of the economic value of avoided hospitalization or surgical procedures) may be limited in CEE. This is a result of hospitals driving their costs by physicians’ salaries, which are much smaller this region.
On the other hand, if the local health status of the population is much poorer, this might mean the capacity to benefit from these medicines could be higher, which means that these medicines may carry significant value for CEE societies. However, this latter case is less common; generally, patented pharmaceuticals are not cost effective in CEE at western European launch prices.
What must physicians consider when deciding between prescribing off-patent and still patent-protected biologics?
Let us say that there is a disease for which we have two biologics available as treatments, and they have very similar effectiveness and side effect profiles. However, the patent for one of these biologics is expiring, so off-patent biologics will soon be available too. From an economic perspective, it would be important for patients to receive an off-patent biologic as first-line treatment and, only if that fails, to explore secondary biological treatment options (i.e. the still patent-protected option).
As a researcher, I think that, in a volume-restricted environment, priority should clearly be given to improve the patient access of those who are denied treatment currently, over the preference of those who would like to stay on an original product.”
The problem that I often observe in CEE region is that off-patent biologics and original, still patent-protected biological medicines, with very similar clinical effectiveness, are in the same treatment line in physicians’ guidelines. As a result, physicians prefer to prescribe the still patent-protected biologics because of their higher prestige and the more lucrative fringe benefits they can expect from manufacturers of original medicines.
This can be problematic because, if there are volume restrictions — i.e. not all eligible patients have access to an original biological medicine — and an off-patent biologic is also available but is not preferred as a first-line treatment, this creates an opportunity cost for the society. It is critical that we are mindful of, and act to minimize, such opportunity costs, as we may otherwise lose the opportunity to generate savings or treat additional patients through increased use of off-patent biological medicines.
We therefore face an interesting dilemma in access-restricted settings: should we consider the preference of patients who are already lucky enough to receive an original biological product and would like to stay on that? Or, should we be considering the access of those unfortunate patients who are currently denied the treatment, as by using off-patent biologicals we may be able to treat more patients?
As a researcher, I think that, in a volume-restricted environment, priority should clearly be given to improve the patient access of those who are denied treatment currently, over the preference of those who would like to stay on an original product.
Where could guidance on deciding first-line treatment recommendations of original and off-patent biologicals come from?
In CEE, I think that a top-down approach for this guidance would be more feasible, driven by payers. Physicians should be provided with amended clinical and financial guidelines clearly outlining a preference to prescribe off-patent biologicals as first-line treatments, so long as there are no significant clinical outcome differences associated with off-patent biologicals and other still patent-protected biological medicines — as is the case with TNF-Î± inhibitors for the treatment of rheumatoid arthritis.
1. Inotai A, CsanÃ¡di M, Vitezic D et al. Policy practices to maximise social benefit from biosimilars. J Bioequiv Availab. 9(4):467—472 (2017).
2. HarsÃ¡nyi A, CsanÃ¡di M, MÃ¡rky K, Vincziczki ÃZ, KalÃ³ Z, Inotai A. Influence of biosimilar infliximab launch on the utilization pattern of biological medicines: the case of Hungary. Expert Rev Pharmacoecon Outcomes Res. 18:1—7 (2019).
AndrÃ¡s Inotai is an employee of the company Syreon Research Institute. Syreon Research Institute has received funding for research from pharmaceutical companies which have biosimilar products.