AVASTIN/LUCENTIS CASE: Italian Council of State makes a further reference for a preliminary ruling to the European Court of Justice, the outcomes of which might be ground-breaking for the Italian legal system

11 May 2021


In the Avastin Lucentis case, that involves the Roche and Novartis Groups, the Italian Council of State makes a further reference for a preliminary ruling to the European Court of Justice, the outcomes of which might be ground-breaking for the Italian legal system.

The case

The Avastin/Lucentis case is, once again, at the centre stage of the antitrust and legal debate in Italy, following the recent reference for a preliminary ruling issued by the Italian Council of State in the context of the action for revision brought by Roche and Novartis against the judgment of the same Council of State no. 4990/2019.

The well-known case at issue concerns two different medicinal products, based on two different active ingredients and with different therapeutic indications: (i) Avastin (Bevacizumab), commercialized by Roche, which is indicated and authorised only for the treatment of oncology patients and is administered through blood infusion; and (ii) Lucentis (Ranibizumab), commercialized by Novartis, which is specifically indicated and authorised for the treatment of the age-related macular degeneration (“AMD”) and is administered through ocular injections.

Because of mere matters of cost, doctors used Avastin as off-label drug (so called “Avastin off-label”), by means of injection in eye, for the treatment of AMD, even after the marketing of Lucentis, which has a specific Marketing Authorization to treat AMD. In reality, however, the so-called “Avastin off-label” is completely different from Avastin, being the result of modifications, on the part of pharmaceutical laboratories, in terms of destination of use; route of administration; dosage; expiration date; packaging; lot number (thus rendering impossible the traceability of the product); and price (which established by the pharmaceutical laboratories).

In 2013, the Italian Antitrust Authority (“IAA”), based on the complaints of the Italian Ophthalmology Society and of an association of private health care facilities, opened the I760 – Roche-Novartis/Farmaci Avastin e Lucentis case. The case was closed in 2014, by a decision of the IAA (the “Decision”) which condemned – and sanctioned for a total amount of over 180 million Euros – the Italian subsidiaries and the parent companies of the Roche and Novartis Groups for having put in place, on the Italian market for the treatment of vascular eye diseases, a horizontal agreement in breach of Article 101 TFEU. [1] According to the IAA, the pharmaceutical groups, raising doubts about the safety of the ophthalmic use of Avastin, created an “artificial difference” between the two medicinal products, aimed at unlawfully maximising the profits deriving from the use of the two drugs, and thus undermining the use of the (less expensive) so-called “Avastin off-label” for the treatment of AMD.

The judicial saga

In 2014, Roche and Novartis appealed the Decision before the Regional Administrative Court of Lazio (“TAR Lazio”). The pharmaceutical companies stressed, in particular, the actual differences existing between Avastin and Lucentis, as well as the inefficiencies and risks for the health deriving from the use of the so-called “Avastin off-label”, which, as mentioned above, does not represent an off-label use Avastin, but an entirely new product, unlawfully marketed by some pharmaceutical laboratories. Finally, Roche and Novartis pointed out that, in any event, in Italy the systematic off-label use of a medicinal product is illegal, in particular, when there is a valid and authorized therapeutic alternative. The TAR Lazio dismissed the appeal of Roche and Novartis with the judgment no. 6122/2014, which was then appealed by Roche and Novartis before the Council of State (i.e., the court of last instance for what concerns the review of public antitrust enforcement decisions in Italy).

By judgment no. 4990/2019 (published on 15 July 2019), the Council of State dismissed the appeal brought against the aforementioned judgment of TAR Lazio, thus upholding the IAA’s Decision. However, before doing so, the Council of State referred to the Court of Justice of the European Union (“CJEU”) five preliminary questions. On 23 January 2018, the CJEU issued its judgment,[2] in which it provided the Council of State with the principles that it should have applied in deciding the Avastin/Lucentis case.

In particular, besides reiterating that “the concept of restriction of competition ‘by object’ must be interpreted strictly […] tak[ing] into account the nature of the goods or services affected, as well as the real conditions on the functioning and the structure of the market […] in question”,[3] the Court of Justice, inter alia, laid down principles that the Council of State, as referring court, should have applied in the case at stake, subject to the verification of factual issues, namely:

  1. 1.- A medicinal product “authorised for the disease concerned” (Lucentis) and a “medicinal product whose marketing authorisation does not cover that treatment but which is used for that purpose and is thus actually substitutable with the former” (Avastin) belong to the same relevant market. However, the actual substitutability of the two medicinal products must be assessed by the competent authorities/courts; therefore, the IAA cannot put its own assessment on the equivalence of two medicinal products before the assessment of the competent authorities;


  1. 2.- Conducts similar to the one put in place by Roche and Novartis would be considered as restrictive of competition “by object” (thus, in breach of Article 101 TFEU) only if the participants in such conducts actually circulated misleading information on the medicinal product used off-label.

According to the pharmaceutical companies, the Council of State failed to comply with these binding principles while deciding the Avastin/Lucentis case. Indeed, the Council of State should have verified, at first, the existence (when the IAA issued the Decision) of assessments/resolutions of the competent authorities on the “conformity of the product at issue with the applicable provisions governing the manufacture or the marketing of that product”. Secondly, it should have verified the actual misleading potential of the information provided by the undertakings to the public.

The Council of State for what concerns the first element, it limited itself to establishing that, at the time when the IAA issued the Decision, no competent authority had issued any decision or opinion on the “potential unlawfulness of the repackaging and prescription terms” for the so-called “Avastin off-label”; this without taking into account the documentation submitted in deeds by the appellants. The same can be said for what concerns the potentially misleading nature of the information provided by the pharmaceutical companies under scrutiny, the assessment of which was entirely omitted by the Council of State.

It is precisely on these grounds that Roche and Novartis brought a further action before the Council of State, asking that Hon. Court for the revision of the ruling n. 4990/2019.

While there is no doubt about the impact that the ruling given at the outcome of the revision lawsuit might have on the case at stake, its actual importance goes far beyond the boundaries of the Avastin/Lucentis dispute. The Council of State issued the order n. 2327/2021 (published on 18 March 2021), referring three questions to the Court of Justice for a preliminary ruling.

The first question concerns who – between the same the same national court of last instance and the CJEU – is entitled to assess the compliance of a decision of a national court of last instance (which, according to the national legal system, cannot be appealed anymore) with the principles established by the CJEU within the same proceedings.

The second question concerns whether the judgment n. 4990/2019 actually breached the principles established by the CJEU in its preliminary ruling of 2018 or not.

Finally, the third one questions the compatibility of the Italian legal system – in which the appeal for revision cannot be brought against judgments of the Council of State that are incompatible with judgments of the CJEU – with several EU provisions.[4]

A straightforward reading of these questions makes clear that, on the one hand, the outcome of the Decision and of the review before the administrative courts is still disputed. On the other hand, the preliminary ruling of the CJEU will not only rule on the Avastin/Lucentis case, but also on the overall Italian legal system. Indeed, as already mentioned, as of today, the Italian legal system does not allow for the revision of judgments of the Council of State that are accused of being incompatible with judgments of the CJEU. Accordingly, a judgment of the CJEU stating that a legal system designed as such is incompatible with EU law undoubtedly scratches the settled principle on the impossibility to review a judgment of a court of last instance. The extent of this scratch may be suitable to be further extended, in the future, to the judgments given by other courts of last instance (e.g. the rulings given by the Court of Cassation) and/or to other kinds of non-compliance. Therefore, the preliminary ruling of the CJEU in this case might lead to a rethinking of the system of judicial reviews in Italy, and to the drafting of a system suitable to strike the appropriate balance between the need to “end” the judicial review and the one to oversee the work of national courts of last instance, whenever possible, in order to ensure the full respect of European Union Law.

Finally, while waiting for the outcomes of the CJEU’s preliminary ruling on this latter reference made by the Council of State, considerate should be considered that Roche took other judicial initiatives in order to assert its rights in the Avastin/Lucentis case.

Indeed, at a national level, Roche appealed the judgment of the Council of State n. 4990/2019 also before the Italian Court of Cassation. The appeal, based on Article 111, paragraph 8 of the Italian Constitution (grounds of jurisdiction), is currently pending.

In this regard, it should be noted that the Joint Chambers of the Court of Cassation, in the context of another case, recently issued an order (n. 19598/2020) by which they made a reference for a preliminary ruling to the Court of Justice. Such reference contains a question that, similarly to the ones recently submitted by the Council of State, challenges the compatibility of the case law of the Italian Constitutional Court that impedes the Court of Cassation from fixing the breaches of EU law put in place by the Council of State (in the framework of the aforementioned procedure pursuant to Article 111(8) of the Italian Constitutions) with several principles and provisions of EU law.[5]

Finally, at a supranational level, Roche also brought a lawsuit against Italy before the European Court of Human Rights (n. 4498/20). In its appeal, Roche complained that the Council of State gave its judgment n. 4990/2019 in breach of Articles 6, paragraphs 1 and 3 (right to a fair trial and right of defence), and 7 (“No punishment without law”) of the ECHR, as well as of Article 1 of the Protocol 1 to the ECHR (“Protection of property”). This lawsuit is currently pending as well.

The ‘strange case’ of Avastin and Lucentis

In light of the above, the ‘strange case’ of Avastin and Lucentis – as it was defined by an authoritative commentator[6] – is not closed at all. The recent reference for a preliminary ruling issued by the Council of State confirms the complexity of the case, the need to clarify important aspects of the decisions of European and national Courts, and the serious problems raised by non-compliance with the principles laid down by the European Court of Justice by means of a judgment.

Elisa Teti – Partner   Alessandro Raffaelli – Partner


[1] The agreement would be based on the fact that Genentech, a subsidiary of the Roche Group, developed both Avastin and Lucentis. However, in Italy, the Roche Group holds the marketing authorization for the sole Avastin, while the Novartis Group holds the marketing authorization for Lucentis. Therefore, the Roche Group receives royalties on Lucentis sales from Novartis.

[2] CJEU, judgment of 23 January 2018, case C-179/16, F. Hoffmann-La Roche and o.

[3] CJEU, judgment of 23 January 2018, case C-179/16, F. Hoffmann-La Roche and o., §§ 78 and 80.

[4] In particular, with Articles 4(3) and 19(1) TEU, and Articles 2(1), 2(2) and 267 TFEU, read in the light of Article 47 of the Charter of Fundamental Rights of the EU.

[5] In particular, with Articles 4(3) and 19(1) TEU, and Articles 2(1), 2(2) and 267 TFEU, read in the light of Article 47 of the Charter of Fundamental Rights of the EU.

[6] L. Pani, he strange case of Avastin-Lucentis. Why does everyone want independent regulatory Agencies that almost nobody ca handle?, Edra, 2017.