The Italian Supreme Administrative Court has just released an articulated judgment (n. 1306 of April 1, 2016) focused on the notion of “therapeutic equivalence” of pharmaceutical products, a concept which, as specified by the administrative judge, is conceptually and legally distinct from that of “equivalent drug” and “biosimilar drug”.

The origin of the notion of “therapeutic equivalence”

The legal definition of “therapeutic equivalence” has appeared following an opinion (AS440 27/12/2007) rendered by the Authority for Competition and Market in the field of public tenders for the supply of medicinal products. The Competition Authority found that it is not correct to hold public tenders for the supply of medicines, grouping and distinguishing drugs with active ingredient patented by off-patent drugs; in fact this division has the practical effect of distorting competition. The Competition Authority had also stated that contracting authorities should structure tenders for drugs that are based on different active principles (whether patented or not) and which, according to the scientific community, have the same therapeutic function. This reasoning is based on the assumption that “… the comparison between the active substances having the same therapeutic properties […] could still achieve short-term savings, without paying the medium-term competitive costs resulting from inadequate dissemination of generic drugs”.

Subsequently, the legislator invested AIFA (the Italian Authority for Drugs) of the task of evaluating from time to time the existence of the requirement of therapeutic equivalence in relation to different medicinal products considered (art. 15, paragraph 11 ter of Legislative Decree 95/2012 converted into Law no. 135/2012).

How to assess the therepeutic equivalence?

In a tender held by the Tuscany region, AIFA has valued the drug Lucentis manufacured by Novartis (used for the treatment of macular degeneration) equivalent, from a therapeutic point of view, to the competing drug Eylea produced by Bayer. Novartis has challenged the view expressed by AIFA and the subsequent invitation to tender of the Tuscany Region, on the basis of a number of reasons, all rejected by both the Administrative Court of first instance (TAR Lazio) and by the Supreme Administrative Court (Consiglio di Stato).

Among the various complaints put forward, the applicant disputed that in absence of a normative notion of therapeutic equivalence, AIFA erred in finding that the drugs Lucentis and Eylea are equivalent from a therapeutic point of view, based on the simple comparison of the therapeutic prescription in the respective products’ leaflet. The judges have rejected the argument, noting that AIFA has instead demonstrated that its statement was based on a much more comprehensive assessment, in which the identity of the therapeutic indications in the respective leaflet was only one of the criteria used, together with the verification of the following: 1) the drugs belong to the same ATC class, to the III or IV level; 2) the drugs exhibit similar route of administration and 3) the drugs possess a similar mode of release of the active ingredient.

The Consiglio di Stato has thus considered that AIFA judgment was properly motivated, free from defects and thus not objectionable.

Therapeutic equivalence does not pesuppose bioequivalence

The applicant also contested the fact that the two drugs showed differences in pharmacokinetics and pharmacodynamics, being pharmacologically different, therefore it was not possible to assess their therapeutic equivalence, since the latter would presuppose the bioequivalence. On this point, the Consiglio di Stato has made it clear that the therapeutic equivalence is a distinct concept from the bioequivalence or bio-similarity and that the first does not presuppose the second.

Bioequivalent are in fact only the biological drugs that are based on the same active ingredient and for which it is established the absence of significant clinical differences, on the basis of pharmacokinetic and pharmacodynamics studies. For bioequivalent drugs it is not necessary to assess the therapeutic equivalence, since once the bioequivalence is demonstrated, the therapeutic equivalence implied.

The evaluation of the therapeutic identity can concern also drugs with different active ingredients and “… it is quite possible that the pharmacokinetics and pharmacodynamics are not identical for the two products, being a task of the competent body assessing whether different modes of action of the two pharmaceutical products can significantly affect their therapeutic equivalence. “

A few days after the publication of the judgment in question, AIFA has also released new guidelines for the evaluation of therapeutic equivalence.