Pöördumine

BACKGROUND MEMORANDUM Date: 24 May 2023 Subject: European Commission's DG SANTE proposal risks destabili- sation of the generic medicines market and access to afford- able treatment for patients 1. CONTEXT Generic medicines are a critical component of EU healthcare provision, allowing national healthcare budgets to achieve significant cost savings and providing patients with affordable access to important medicines. Polpharma Pharmaceutical Works S.A. (Polpharma), Zentiva Pharma GmbH, Neuraxpharm Pharmaceuticals S.L. and several other generic medicines man- ufacturers currently have valid marketing authorisations (MAs) to market a generic version of the multiple sclerosis treatment, Tecfidera. It is a “blockbuster” product which has been mar- keted in the EU since 2014 by U.S. company Biogen. The European Commission is currently initiating several measures which attempt to block these generic products from the market. A proposal for an amendment that would have a devastating impact on the marketing of generic versions of Tecfidera and other generic medicines in Europe has been put before the Standing Committee for Medicinal Products for Human Use for vote on 30 May 2023. In our view, these ongoing and proposed actions clearly demand further scrutiny since:  there is a risk that they will lead to unpredictable, widespread disruption and confu- sion in the EU generics market, with negative consequences for patients and Member States’ healthcare provision; and  the legality of the measures is uncertain and disputed by the generic companies. It is therefore essential that legislation is applied correctly, to facilitate the development of a sector that is vital to European consumers/patients as well as to EU commercial interests. 2. BRIEF BACKGROUND The large U.S. company, Biogen, was granted an MA for Tecfidera in 2014. At the time, DG SANTE concluded that the company should benefit from a full period of regulatory data pro- tection (RDP), together with market protection against generic competition until 2024 at the earliest1. This outcome was reached only after lengthy discussions involving DG SANTE, the European Medicines Agency (EMA) and Biogen, the debate arising due to Tecfidera’s similarity to another Biogen product, Fumaderm. Tecfidera contains dimethyl fumarate (DMF) as its 1 Regulatory data and market protection is provided for “originator” (or “reference”) products by the pharma- ceutical legislation; only once the regulatory data protection period expires may MAs for generic versions of the reference product be sought, based on an “abbreviated” application which relies in part on data in the reference product MA dossier. Such products may only be placed on the market once the market protection expires. The appropriate scope and length of these periods was carefully considered by legislators when adopt- ing these provisions, bearing in mind the importance of achieving a balance between the interests of the orig- inator and the generics sectors, so it is important that the wording and intention of the legislation is fully respected. Bird & Bird (Belgium) LLP is a limited liability partnership, registered in England and Wales with registered number OC425817. Bird & Bird is an international legal practice comprising Bird & Bird LLP and its affiliated and associated businesses in the locations listed, which include Bird & Bird (Belgium) LLP. Bird & Bird (Belgium) LLP is registered in Belgium under the enterprise number 0722.579.922 and practices under the VAT number BE0722.579.922. active substance and Fumaderm, authorised in 1994 by the German regulatory authority, is stated to contain both DMF and three monoethylfumarate (MEF) salts as active substances. Under the RDP rules, where one company has authorisations for two products with the same constituent active substance(s), the RDP and market protection periods for the second author- ised product expire at the same time as the protection periods for the first. Polpharma had gathered scientific evidence establishing that the MEF salts in Fumaderm do not in fact make any therapeutic contribution within that product. Once it is confirmed that Tecfidera and Fumaderm in fact have the same active substance profile (namely DMF only), the RDP rules confirm that Tecfidera’s RDP eligibility has long since expired, based on Fuma- derm’s authorisation in 1994. This in turn secures a right to apply for an MA for a generic version of Tecfidera rather than having to wait until the alleged RDP period had expired. When the EMA refused to accept Polpharma’s generic MA application (filed in 2018), the company challenged the Commission’s position on Tecfidera’s RDP by bringing an action in the General Court (Case T-611/18). The Court agreed with Polpharma’s arguments, finding that the Com- mission had used the wrong test when deciding that Tecfidera should benefit from independ- ent RDP. Following the Court’s judgement, the EMA accepted a new, separate generic MA application from Polpharma and in 2021 performed a detailed scientific assessment of all avail- able evidence. The EMA concluded there is no evidence to support the proposition that Tecfid- era and Fumaderm have different active substance profiles. Having established that fact, the RDP claimed for Tecfidera could no longer be upheld on scientific and legal grounds, and the Commission granted several generic MAs. 3. APPEAL OF THE GENERAL COURT JUDGMENT AND ITS CONSE- QUENCES The EMA, the Commission and Biogen all appealed the General Court’s ruling, and the Court of Justice (CJEU) delivered its appeal judgement on 16 March 2023 (joined appeal Cases C- 438/21 P, C-439/21 P and C-440/21 P). This overturned the General Court’s ruling. However, this judgement is of no relevance to the validity of the generic MAs, all of which were granted under separate procedures and after the regulatory authorities acquired knowledge of new sci- entific evidence confirming the identical active substance profiles of Tecfidera and Fumaderm. DG SANTE and Biogen appear to believe that the CJEU judgment in some way reactivates Tecfidera’s RDP and market protection until February 2024 at the earliest2. DG SANTE has introduced a series of measures which misinterpret the scope of the CJEU judgment. It is im- portant to be aware that this judgment:  makes no statement regarding the validity of the generic MAs granted by the Commis- sion. In fact, these are the subject of separate proceedings brought by Biogen in the General Court and a judicial ruling regarding validity is still pending;  contains no statement suggesting that Tecfidera is still entitled to RDP and market protection (which it is not, given the facts that have been established more recently);  in no way suggests that the RDP test eventually applied, based on scientific evidence and confirming that Tecfidera has no ongoing RDP/market protection, is invalid. It should be emphasised that the litigation concerned Polpharma’s first (rejected) application for an MA in 2018, and the CJEU judgment was limited (in law) to addressing the validity of the EMA’s actions at that point in time. The judgement merely confirms that that EMA did not 2 The Commission also claims that legislative provisions allow this period to be extended until February 2025, although this appears to have no legal basis and is currently under judicial review. 2 commit a manifest error of assessment on 30 July, 2018 when the EMA considered that Tecfid- era still benefitted from RDP. There is therefore no basis for DG SANTE’s claim that this judg- ment confirms Tecfidera’s ongoing market protection. The generic MAs eventually granted were all based on separate procedures which relied on the 2021 scientific assessment specifi- cally establishing that there is no evidence supporting a therapeutic contribution of MEF within Fumaderm. In taking a series of actions to attempt to force the generic products off the market, DG SANTE not only misinterprets the scope of the CJEU judgment but also fails to take into account the relevant facts known to it since the EMA’s 2021 scientific assessment. These facts confirm that Tecfidera has no ongoing market protection, as a matter of correct application of the law. 4. EUROPEAN COMMISSION’S PROPOSAL TO STANDING COMMITTEE Various actions are being undertaken by the European Commission’s DG SANTE, with the stated purpose of enforcing the CJEU judgment, none of which appear to have a legal basis. The one of most immediate concern is a proposal to amend the generic MAs granted by the Commission to include a statement that the generic “shall not be placed on the market before the expiry of the marketing protection period of [Tecfidera].” A proposal for this amendment has been put before the Standing Committee for Medicinal Products for Human Use under a procedure launched on 9 May 2023. A shortened 5-day procedure was originally proposed but due to objections from Member States this amendment will now be debated in a full Standing Committee meeting on 30 May 2023. This proposal aims to block market access for generic products and, if adopted, it would have broad, detrimental consequences for the EU generics market. The proposed amendment would create great uncertainty for MA holders and regulators. Specifically:  the Commission appears to be appropriating a right to enforce the market protection period against generic products. The proposed amendments to granted MAs lack any legal basis, and could have unpredictable consequences for national regulators and MA holders; and  the legal consequences of including the proposed statement in the MAs as a means of “confirming” market protection are very unclear and may differ between Member States. This would lead to uncertainty over whether all generic MAs should contain an equivalent statement in order for applicable market protection to be “valid”. This proposal therefore concerns a legally questionable interpretation of the legislative frame- work. Disruption of the market for generic products due to resulting legal uncertainty could have serious implications for healthcare provision at Member State level, and for patients’ ac- cess to a wide range of generic medicines. Furthermore, asserting ongoing market protection for Tecfidera is, in our view, clearly illegal given the outcome of the EMA’s 2021 robust scien- tific assessment. 5. URGENT SCRUTINY OF COMMISSION’S PROPOSALS REQUIRED Biogen has challenged the validity of the MAs for generics of Tecfidera granted by the Com- mission (Cases T-278/22, T-279/22, T-269/22 and T-268/22). The cases are ongoing, and the General Court has not yet had the opportunity to rule on the validity of these MAs, which is underpinned by the question of the validity of Tecfidera’s RDP. The only institution legiti- mately entitled to verify these issues is the General Court, in the context of this litigation. In concluding that the generic MAs granted after 2021 are currently subject to Tecfidera’s ongoing market protection, without any clear legal basis for this view, the European Commission is attempting to substitute its own judgment for that awaited from the General Court. This is 3 clearly premature and inappropriate. Currently, all the generics of Tecfidera have valid, un- conditional MAs. Many patients in Europe who have switched to or started treatment on ge- neric versions of Tecfidera now face the threat of their treatment becoming unaffordable and/or unavailable. The European Commission’s actions, which have created this risk, must be scrutinized as a matter of urgency and any such actions should be suspended until the Gen- eral Court has ruled on this question. For further information, contact: Marc Martens Bird & Bird LLP E-Mail: [email protected] 4 Saatja: Paolo Sasdelli <[email protected]> Saadetud: 25.05.2023 19:31 Adressaat: <"SM Info"> Koopia: Marc Martens <[email protected]>; Sarah Faircliffe <[email protected]>; Francine Cunningham <[email protected]> Teema: Letter regarding generic medicines market Manused: 20230525 Letter regarding generic medicines market.pdf; 20230523 - Background memorandum.pdf Dear Minister, On behalf of our clients Polpharma Pharmaceutical Works S.A. (Polpharma), Zentiva Pharma GmbH (Zentiva) and Neuraxpharm Pharmaceuticals S.L. (Neuraxpharm), we are writing to raise our urgent concerns regarding the European Commission’s recent activities attempting to block market access for certain generic medicines to treat multiple sclerosis. In particular, the Standing Committee for Medicinal Products for Human Use will vote on 30 May on a proposal put forward by DG SANTE for amendment of certain relevant marketing authorisations (MAs). This amendment could have a profoundly detrimental impact on the market for generic medicines in the European Union and on patient access to such affordable medicines. Please see attached the letter expressing our clients’ concerns together with a more detailed background of the situation at hand. We would therefore ask you to ensure that this proposal does not go ahead without your full national scrutiny and understanding of the consequences for healthcare provision in the EU and European patients. Best Regards, Marc Martens Partner Bird & Bird [email protected] Direct +32 (0) 2 282 6090 Mob +32 479 99 64 60 Tel +32 2 282 6000 Fax +32 2 282 6011 On behalf of Polpharma, Zentiva and Neuraxpharm Transparency Register ID no: 594629632551-37 BIRD & BIRD For information on the international legal practice comprising Bird & Bird LLP and its affiliated and associated businesses (together "Bird & Bird"), our offices, our members and partners, regulatory information and complaints procedure see www.twobirds.com/en/more-information/legal-notices Our privacy policy, which describes how we handle personal information and the use of cookies is available at www.twobirds.com/en/more-information/privacy. If you would like to opt-out of receiving marketing communications from Bird & Bird click here: http://www.twobirds.com/unsubscribe/ Any e-mail sent from Bird & Bird may contain information which is confidential and/or privileged. Unless you are the intended recipient, you may not disclose, copy or use it; please notify the sender immediately and delete it and any copies from your system. Bird & Bird (Belgium) LLP, a limited liability partnership, registered in England and Wales with registered number OC425817, has its registered office at 12 New Fetter Lane, London EC4A 1JP and is an affiliated business of Bird & Bird LLP which operates in Belgium through its Permanent Establishment in Brussels. Avocat or Advocaat are members of Ordre français des avocats du Barreau de Bruxelles or De Nederlandse Orde van Advocaten bij de balie te Brussel and regulated as described at on barreaudebruxelles.bes or baliebrussel.be Our Ref: PHAWO.0029 Brussels, 25 May 2023 Dear Minister, Re: European Commission's DG SANTE proposal risks destabilisation of the generic medicines market and access to affordable treatments for patients On behalf of our clients Polpharma Pharmaceutical Works S.A. (Polpharma), Zentiva Pharma GmbH (Zentiva) and Neuraxpharm Pharmaceuticals S.L. (Neuraxpharm) we are writing to raise our urgent concerns regarding the European Commission’s recent activities attempting to block market access for certain generic medicines to treat multiple sclerosis. Of immediate concern, the Standing Committee for Medicinal Products for Human Use will vote on 30 May on a proposal put forward by the Commission’s DG SANTE for amendment of certain relevant marketing authorisations (MAs). As explained below, this amendment could have a profoundly detrimental impact on the market for generic medicines in the European Union and on patient access to such affordable medicines. DG SANTE has proposed adding a specific statement to the generic product MAs, referring to the disputed market protection of the multiple sclerosis medication, Tecfidera. This reference would state that the generic “shall not be placed on the market before the expiry of the marketing protection period of [Tecfidera].” In effect, this amendment would mean that European manufacturers of the generic version of Tecfidera will no longer be able to market their products in the EU and European consumers will no longer have access to this lower cost treatment option for a serious medical condition. The only beneficiary of such an amendment would be Biogen, the U.S. manufacturer of Tecfidera which has marketed this “blockbuster” product in the EU since 2014. Such a change would be made at the expense of European consumers’ access to the generic version of this important medicine. The Polish generic medicines manufacturer, Polpharma has been engaged in ligation in the European Courts to secure their right to market a generic version of the medicine Tecfidera in the EU. The litigation concerned the question of whether Tecfidera currently still benefits from RDP, the rules for which are set out in EU pharmaceutical legislation and determine when an authorized generic may finally be placed on the market. The General Court’s judgement in this litigation has allowed several companies, including Polpharma, Neuraxpharm and Zentiva, to secure unconditional MAs for generic versions of Tecfidera, and these products are currently available to EU patients. Importantly, not long before these MAs were granted, the Commission was made aware of important new evidence following a scientific assessment conducted by the European Medicines Agency (EMA) in 2021. The EMA concluded that there is currently no evidence to support a view that another Biogen product, Fumaderm, contains different active substance(s) from those in Tecfidera. Bird & Bird (Belgium) LLP is a limited liability partnership, registered in England and Wales with registered number OC425817. Bird & Bird is an international legal practice comprising Bird & Bird LLP and its affiliated and associated businesses in the locations listed, which include Bird & Bird (Belgium) LLP. Bird & Bird (Belgium) LLP is registered in Belgium under the enterprise number 0722.579.922 and practices under the VAT number BE0722.579.922. In view of this newly established fact, and due to the widely accepted interpretation of the legislative provisions, it cannot be disputed that the law on RDP confirms that these generic MAs were properly granted. Furthermore, Tecfidera does not benefit from any ongoing market protection which could prevent the marketing of the generic products in the EU. However, the General Court ruling was appealed and overturned on 16 March 2023. Since this date, the European Commission and Biogen have used the ruling to justify various measures aimed at forcing the generic products off the market. Discontinuing the supply of affordable generic products to European consumers - without a clear legal basis - would have serious repercussions for patient welfare and requires robust justification. In this context, we firmly believe that the European Commission is misinterpreting the scope of the CJEU judgement and is failing to recognise crucial scientific facts that have been established since 2021. Tecfidera’s current lack of market protection entitlement was not addressed in the CJEU judgement because this question was outside the scope of that particular case. The European Commission therefore has no justification for now relying on this judgement to block market entry for generic products in a way that dismisses its own later, more robust conclusion regarding Tecfidera’s lack of market protection. (Please see memorandum in annex for a detailed explanation). Furthermore, there are ongoing cases focused on the granting of market authorisations for the generic products still underway in the General Court. As yet, there is no judicial ruling regarding the validity of these MAs. In concluding that the generic MAs granted after 2021 are currently subject to Tecfidera’s ongoing market protection, without any clear legal basis for this view, the European Commission is attempting to substitute its own judgement for that awaited from the General Court. As such, the current proposal is premature and goes beyond the Commission’s area of competence. To conclude, adoption of the proposed amendment would have wide implications far beyond this case and result in huge legal uncertainty for MA holders and regulators. We therefore respectfully ask you to intervene with the European Commission and your responsible services to ensure that this approach is reconsidered to take full account of the serious implications of the proposed amendment for European consumers and for generic medicines manufacturers, who are such a vital component of the life sciences industry sector. This proposal should not go ahead without full scrutiny and understanding of the consequences for healthcare provision in the EU and European patients. Yours faithfully Marc Martens Bird & Bird LLP On behalf of Polpharma, Zentiva and Neuraxpharm 2