We present an excerpt from the Position paper dell’Istituto Bruno Leoni (IBL) sui farmaci biosimilari.
In fact, if universal health seems 'free', it is not at all: tax payers pay for it, through public spending, and the economy itself which revolves around health, through the investments necessary for the development of services and products. Health, therefore, has a cost, made up of fixed components and other more variable ones. Among the latter, pharmaceutical expenditure, 
However, there are some shadows: both the concept of universal and fundamental right to health is the case, for example, of prescription for active ingredients, or of 'conflicts of interest' between savings objectives and treatment objectives. Finally, it is the case of biosimilar drugs with respect to the originators.
The concept of "biosimilar drug" was introduced by the European Union Directive 2001/83/EC, transposed in Italy by the legislative decree n. 219/2006, according to which "when a biological medicinal product similar to a reference biological medicinal product does not meet the conditions of the definition of generic medicinal product due, in particular, to differences in raw materials or differences in the production processes of the biological medicinal product and of the reference biological medicinal product, the applicant is required to provide the results of the appropriate preclinical tests or clinical trials relating to these conditions" [ed: art. 10 paragraph 7]
The development of biological medicines is not immediately and easily transferable from one laboratory to another, unlike traditional medicines, leading the scientific community to conclude that the production process of these medicines is so characteristic that it itself constitutes, in a certain sense, the finished product.
From these differences emerges the need to provide for a different and more complex authorization process for biosimilars compared to generic drugs.
In 2017, consumption of the eight biosimilar molecules on the market in Italy grew by 74% compared to the previous year, reaching 19% of total consumption (originators and biosimilars).
E’ assolutamente necessario che vi sia chiarezza ed esatta definizione delle responsabilità di ciascuna delle istituzioni coinvolte nella tutela della salute, per evitare che gli già precari equilibri in gioco tra esigenze di risparmio, diritto alla salute e necessità di ritorno degli investimenti in ricerca e sviluppo non compromettano ora l’una ora l’altra di tali esigenze.
The marketing authorization procedure for biosimilar medicines, envisaged in the guidelines periodically published by the EMA, is different from that envisaged for generic medicines. While for the latter it is sufficient to present the results of bioequivalence studies, biosimilars – containing an active ingredient similar, but not identical to that of the reference biological medicinal product – require demonstration of its comparability with the originator product.
Among the interpretative doubts addressed by the regional administrative courts and by the Council of State, the most important concern on the one hand the recognition of substitutability, on the other the recommendations and prescriptive constraints by the regions.
The most controversial issue that emerges from the jurisprudence on biosimilars is certainly that relating to the conditions and limits within which the Regions can encourage the prescription of certain drugs, to the detriment of others, by local health authorities and doctors, especially where this need is motivated not by clinical reasons, but by public finance.
The Council of State has recognized the unavoidable need for the recognition of therapeutic equivalence by AIFA, and the consequent illegitimacy of the regional measures adopted in the absence of this prior assessment.
Among the many balances at stake, the Council of State reiterates the respect for the prescribing autonomy of the doctor. The Regions, therefore, can certainly recommend the use of certain medicines, also taking into account a possible saving expected from this choice by doctors, while they cannot bind treating doctors and managers of health facilities to precise economic results, nor to all the more reason to monitor the degree of achievement of these results. The provision of defined objectives and their monitoring, in fact, inevitably affect the treating doctor, not guaranteeing the doctor's necessary autonomy in the evaluation of individual cases and individual exceptions to the recommendations of the regions (Cons. State, section III, no. 4546/2017. See also Lazio Regional Administrative Court, section III, no. 2671/2018, and Lazio Regional Administrative Court, section III, n.2650/2018).
Nel documento del marzo 2018, l’AIFA ha aggiunto al quadro individuato la considerazione che – per quanto la scelta di trattamento rimanga una decisione clinica affidata al medico prescrittore – a quest’ultimo sia anche affidato il compito di contribuire a un utilizzo appropriato delle risorse ai fini della sostenibilità del sistema sanitario”.
Considerato però che “il rapporto rischio-beneficio dei biosimilari è il medesimo di quello degli originatori di riferimento” – l’AIFA “considera i biosimilari come prodotti intercambiabili con i corrispondenti originatori di riferimento”. Inoltre, tale considerazione vale “tanto per i pazienti naive quanto per i pazienti già in cura”.
How can a system be truly universalistic in which pharmaceutical expenditure must be "commensurate with actual financial resources, which condition the quantity and level of healthcare services", [Constitutional Court, n. 356/1992] and in which the prescriber is entrusted with the task not only of treating patients, but "of contributing to the appropriate use of resources for the sustainability of the health system"? [AIFA, Second AIFA Position Paper on Biosimilar Medicines, 27 March 2018, p. 22].
In a healthcare system that proclaims that it universally guarantees the right to health, the risk is that this common thread generates an illusion of access to care which, on the other hand, hides a much more complex and critical reality. The cost certainly cannot represent a priority criterion of choice for the regulator, if only with respect to other criteria such as health safety and people's health, in a model that really wants to be called universal.
The risk that the technical/scientific assessments that should guide the action of the legislator, AIFA and the regions end up favoring financial needs over clinical ones, thus jeopardizing the autonomy and freedom of doctors, with questionable effects both from the point of view of the objectives of cost containment and, a fortiori, from the point of view of the protection of collective health. General managers and doctors, in some cases, may find themselves having to resolve a real conflict of interest.
In this sense, it must be taken into consideration that greater resources saved by the regions on the cost of healthcare do not necessarily correspond to greater resources for citizens, but instead risk taking the form of sums of public money reused by the regions for purposes whose opportunity should at least be evaluated previously, from a cost-benefit perspective, with respect to pharmaceutical expenditure.
In linea generale, pertanto, l’utilizzo di farmaci biosimilari o originator dovrebbe corrispondere alle diverse e specifiche casistiche, valutate secondo criteri medico-scientifici dai medici curanti, in autonomia e potendo godere di responsabilità e di libertà prescrittiva. Una prospettiva, quest’ultima, confermata anche dall’AIFA, che ha recentemente ritenuto la discrezionalità riconosciuta al medico alla stregua di “una garanzia per i pazienti”.
A different direction, aimed at selecting treatments and therapies on the basis of accounting reasons, could compromise the right to health as conceived in our legal system. But that's not all: intervening downstream on the problem of the cost of public health is, for the umpteenth time, an attempt to deny the citizens themselves that that problem exists, effectively making it worse over time. If, on the contrary, we wanted to correctly address the problem from its roots, we should declare in a transparent way that the national health system charges itself with a series of costs that not only exist, but which are, at present, less and less sustainable in the face of the universalistic goal.
This would be the way to start giving credit to healthcare models which, without failing in the duty to guarantee health, do not superimpose it on an exclusively public and performance model.
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THE BIOSIMILAR MARKET FROM JANUARY TO JUNE 2018
Nel primo semestre 2018 le 10 molecole biosimilari in commercio sul mercato italiano – Epoetine, Filgrastim, Somatropina, Follitropina alfa, Infliximab, Insulina Glargine, Etanercept, Rituximab, Enoxaparina e Insulina Lispro, per un totale di 45 prodotti – hanno assorbito il 12% dei consumi nazionali contro l’88% detenuto dai corrispondenti originator.
On an annual basis, the pool of biosimilars present on the national market recorded an overall growth of 27.7% compared to the first half of 2017, calculated net of new entries, i.e. the new biosimilar molecules launched on the market only from June 2017 (Rituximab, Enoxaparin and Insulin Lispro), against a contraction of the biological originators of 1,6%.
Spotlights on the performance of the 3 molecules protagonists of the "overtaking" compared to the biological originator. Filgrastim achieved the highest degree of penetration on the market, whose 5 biosimilars on the market absorb 94.68% of the market in volumes (89.35% in values, at average price). Epoetins follow (75.39% of the relative market in terms of volumes and 62.12% in values), on the market in a biosimilar version, on a par with filgrastim, starting from 2009.
Ancor più notevole la prestazione dei biosimilari di più recente o recentissima registrazione: Infliximab, in versione biosimilare dal febbraio 2015 e titolare nel primo semestre 2018 del 69,75% del mercato a volumi (54,67% a valori); Follitropina alfa, in pista dall’aprile 2015 e oggi titolare del 12,69% a volumi (12,36% a valori); Insulina Glargine -primo biosimilare in commercio da febbraio 2016 – oggi concentra il 17,03% a volumi (12,64% a valori). Risultato anche migliore per Etanercept (in commercio da ottobre 2016), che nel I semestre dell’anno ha assorbito il 29,03% a volumi (23,26% a valori) e il Rituximab, in commercio dal luglio 2017, che nella versione biosimilare concentra già il 40,66% dei consumi (26,28% a valori).
The picture of consumption at the regional level is diversified but still growing. Valle d'Aosta and Piedmont record the highest consumption of biosimilars for all the molecules on the market: in both they share 41.89% of the market on the overall reference market and even 80.25% of the market referred to the five molecules on the market for at least 3 years (Epoetine, Filgrastim, Somatropin, Infliximab, Follitropin Alfa).
The same pool of older commercialized molecules obtains significant consensus in practically all the Regions (Tuscany, 70.24%; Veneto 64.27%; Sicily 59.52%; Liguria, 72.21%; Emilia Romagna, 63.89%). Rear lights Abruzzo (36,79%) and Calabria (14,95%).
The ranking varies by extending the analysis to all the biosimilars on the market: after removing the aforementioned primacy Piedmont and Valle d'Aosta are followed in the ranking by Sicily (18.82% of the total market), Basilicata (14.79%), Friuli Venenzia Giulia (13.341 TP3T), Tuscany (12.72%). All the other Regions are below the national average; taillights Puglia and Umbria which do not even reach the 5% of consumption.
Patent expirations and potential savings. According to a very recent analysis prepared by the IQVIA study centre, the market value of the main organic products that will lose their patent protection between 2018 and 2022 amounts to around 1 billion euros. For the seven molecules in question (adalimumab, trastuzumab, bevacizumab, insulin lispro, ranibizumab, teriparatide, pegfilgrastim), in the absence of competition from any biosimilar, a cumulative expenditure of approximately 5.6 billion is estimated over the next five years.
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