Biosimilars in Italy: a new regime
Since the approval of the first biosimilar in Europe, in 2006, biosimilars have gained momentum. Currently, 25 biosimilars have been centrally approved in the EU, and over a dozen biosimilar applications are under evaluation by the European Medicines Agency. Their number is likely to increase substantially in the next few years due to the upcoming patent expiry of several blockbuster biologics.
With the increasing constraints on healthcare budgets, many European countries look at biosimilars as an opportunity for substantial financial savings, and Italy is no exception. In fact, it is expected that the use of biosimilars will result in cost cuts for the Italian healthcare sector amounting to up to €460 million ($480 million) per year.
In 2016, Italy adopted measures that reorder and clarify the legal framework governing the use of biosimilars. These include the publication of a new concept paper on biosimilars by the Italian Medicines Agency (AIFA), and the adoption of specific rules on the substitutability and public procurement of biologics. Overall, these measures should favour a rise in the market uptake of biosimilars, although probably not at the pace that Italian payors would like to see.
The principal traits of the Italian biosimilar regulatory landscape, as modified by these recent changes, are outlined below.
Pricing and reimbursement
Medicinal products, including biosimilars, must have a pricing and reimbursement status in order to be placed on the Italian market. If the marketing authorisation holder (MAH) intends to seek reimbursement, it must submit a specific request to AIFA and negotiate the reimbursed price with the agency.
Italian law requires that the MAH of a generic product offer at least a 20% discount against the price of the originator in the context of the pricing negotiations with AIFA. AIFA’s concept paper clarifies that the agency applies this rule to biosimilars. Historically, price discounts for biosimilars have been higher than 25%.
Moreover, biologics (and biosimilars) may be included in the so-called ‘648 List’ of off-label uses reimbursed by the Italian National Health Service. For example, Remicade (infliximab) has been included in the 648 List for the treatment of severe refractory uveitis correlated with juvenile idiopathic arthritis. However, AIFA’s concept paper makes clear that the inclusion of the biologic originator in the list does not trigger the automatic inclusion of its biosimilar(s). In fact, until now, biosimilars of Remicade have not been included in the 648 List.
Substitutability of biosimilars
The extent to which biologics may be automatically substituted with their biosimilars has been the subject of lively public debate in Italy over the past few years. Most recently, the Italian regions have advocated an automatic substitution regime, but the 2017 Budgetary Law, adopted in December 2016, has introduced an express prohibition against automatic substitution.
AIFA’s concept paper on biosimilars confirms that automatic substitution is not permitted and indicates that physicians should decide on a case-by-case basis whether to treat a patient with a biosimilar or innovator biologic. However, it also provides that “biosimilars constitute a therapeutic option whose risk-benefit balance is identical to that of their originators.”
“The 2017 Budgetary Law, adopted in December 2016, has introduced an express prohibition against automatic substitution.”
This constitutes an important change compared to the previous version of the paper, which expressly recommended the use of biosimilars only in patients who have not been previously treated with a biologic (naïve patients). This suggests that AIFA is open to more biosimilar-switching in non-naïve patients.
The Italian Competition Authority has expressed concerns about such “rigid exclusion of any possible automatic substitutability between an originator and its biosimilar versions, and between different biosimilar versions of the same originator”, in particular because of possible future developments on biosimilar substitutability.
Public procurement and promoting uptake
The Italian healthcare system is highly decentralised, and each of the 20 Italian regions is financially accountable for the pharmaceutical expenditure in its territory. It is not surprising therefore that regional payors have historically used public procurement to encourage the use of biosimilars, primarily to achieve financial savings. However, in the absence of specific national rules on public procurement of biologics, the procurement policies and regulations on biosimilars adopted by the Italian regions have been highly fragmented and inconsistent.
Recurring requirements of these regional measures are that:
