A letter to a patient representative on Adaptive Licensing / pathways

by Yannis Natsis, 13 May 2015

Dear Bettina,

Many thanks for taking the time to comment on my analysis on adaptive licensing/pathways entitled “Adapting medicines to the market or to patients’ needs”. Interventions like yours are necessary and certainly help the debate move forward. Let me start by expressing my firm belief that we share the same goals as we both strive to ensure access to the right treatments for all those who need them. At the end of day, we are all potential patients who are entitled to enjoy the highest quality the healthcare system has to offer.

To this end, I am glad we agree on an additional imperative that of denouncing the immorality of exorbitant drug prices which in fact deprive tens of thousands of people in Europe today of their treatments. As you rightly underline, the profiteering character of the current business-driven pharmaceutical model results in medicines whose primary adverse effect is “financial toxicity”.

As regards adaptive licensing (henceforth AL), there is a series of serious questions that remain unanswered. I am confident that we agree that when it comes to such complex topics, a comprehensive and unbiased debate is mandatory. AL puts patient advocates in the spotlight and with that comes increased responsibility and higher expectations for accountability. In the words of the EMA’s Guido Rasi “patients will play an even bigger part in the drug development process but need to be distanced from the emotional involvement in the product under evaluation”.

Unmet need” is supposed to be the defining criterion of the scope of application of adaptive licensing…but wait, we do not even know what falls under unmet medical need

Theoretically, AL aspires to address the needs of patients that fall under this category. This is of pivotal significance in the course of the debate because “unmet medical need” not only constitutes the starting point but more notably defines the scope of application of AL. In other words, the candidate drug must present a real advance for patients in areas of unmet need. However, European countries have always had a very hard time reaching a consensus on a definition. The current stalemate in the respective negotiations at the recently established European Commission Expert Working Group on Safe and Timely Access to Medicines for Patients (STAMP) confirms the difficulties. This is hardly surprising as apart from the scientific criteria used to delimitate unmet need, numerous political, economic and societal aspects come into play and thus vary considerably between member states. This is a profoundly important point, as pricing & reimbursement decisions depend on this definition. It is remarkable that the European Commission as well as the European Medicines Agency (EMA) are quick to dismiss any fears that AL will apply to all medicines and are eager to stress that it covers unmet need only. But how can we rest assured that the exception will not become the rule when unmet need is so controversial and vaguely defined? It is totally unclear to me how it will be established and I am not the only one to find this puzzling.

Real world clinical trial data collection sounds good but how, who, what, when?

Another key component and insurmountable “If” in the case of AL, is the collection of real-world clinical trial data (hereafter RWD). As you acknowledge in your response, AL’s success and credibility depend on this. In fact, the roots of the AL debate are not about improving access but about redesigning the clinical trials model and promoting the adaptive trials narrative. The current randomized controlled trials (RCT) model usually requires lengthy trials, a significant cost for industry and most importantly a numerous products fail after a lot of money has been spent. AL entails instead a well-defined subpopulation implying very limited initial clinical trials where efficacy will be demonstrated quickly (contrary to patient safety) and that will lead to a gradual expansion. It is common ground that AL shifts the paradigm prioritizing efficacy over safety which in the case of certain categories of patients makes absolute sense. But again, this can only be the exception and not the rule. This means that industry gets to save a lot of money while managing to place its expensive products on the market much earlier than ever before. Moreover, it is not sure that a novel trial design will facilitate the AL, nor how the additional data will be collected, what type of data will be collected, who will collect it, who will pay for this and over what period. Needless to mention, that how this data will be evaluated scientifically and by whom are crucial questions in relation to their reliability and objectivity.

We need the products on the market”. Great, but at what price?

Let’s talk about money. Another challenging and pretty tangible problem is the question of pricing and reimbursement of these drugs. They rely on much fewer clinical trial data, their efficacy looks good (the benefit-risk analysis is positive since theoretically at least, we should be talking about patients with a higher risk profile) and they cover the needs of a small group of patients. Industry claims that since the volume is small, the price should be high, whereas countries fearful about their health budgets argue that since the volume is small, the price should be small as well. As a consumer and potential patient, I wonder how these products will be reimbursed especially during the initial authorization. There is considerable concern about this in the Council too. Another critical question often asked is on what grounds the price will be reviewed.

What if it goes wrong?

I must say that I am a bit surprised with your stance towards safety. In my opinion, society should aim to safeguard the maximum degree of both safety and efficacy. Furthermore, I strongly disagree with the view that patient safety regulations stifle access. Of course, the system as I indicate in my original analysis already foresees the necessity to live with increased uncertainty for very specific groups of patients and accommodates this through the current fast track mechanisms (conditional marketing authorization-CMA, accelerated procedure, compassionate use schemes and others). One of the fundamental questions that AL fails to effectively resolve is what will happen if the advertised benefits of candidate drugs are not confirmed in the populations targeted. I am particularly concerned about this as we are fully aware that most member states neither have the administrative capacity nor the political will to withdraw products once they are on the market. This issue cannot be pushed aside as the liability for whatever goes wrong does not fall on the companies but on public authorities. AL relies heavily on enhanced post-marketing safety and efficacy surveillance to manage this increased uncertainty. It is erroneous to believe that the EU Pharmacovigilance system –seen as excessively demanding, disproportionate and counter-productive by industry, hailed as a success by public health advocates- can or should carry the burden of this monitoring. It was not set up for this reason in the first place.

Why not work with what we already have?

Pharmaceutical companies must reconsider their negative view about the present fast track instruments and commit themselves to enhance them. They prefer full marketing authorization over CMA mostly because they are not 100% certain that they will obtain reimbursement when complete data are not available. As you probably know, STAMP is conducting a review. It is collecting experiences and best practices from member states via concrete questionnaires on how they implement these schemes, what the various criteria and obstacles are etc. This mapping exercise is significant as its findings will feed into ongoing discussions and will define the need or not to redesign the EU market access system. At the same time, the EMA’s Committee for Medicinal Products for Human Use (CHMP) is revising the draft Guideline on the CMA. There is no doubt that today’s options can be improved. Patient groups have an obligation to actively and constructively contribute to the ongoing evaluations (on the member state level too) and to work on improving the inadequacies. I hope that the findings of these reviews will be unbiased and will genuinely aim to develop the current system, tailor it better to the needs of patients and make it more efficient.

What is the big picture about AL? Is it only about access to medicines?

No, its scope and impact are much broader. This is the so-called life-cycle approach to drug development with far-reaching implications across the entire regulatory framework. In a nutshell, industry is not happy with the fact that high prices have become a political issue on an EU level. It is thus trying to shift attention away from the subject and to reshape the agenda by putting fast & early access on top of it. Their long-term strategic goal is to restructure the EU medicines regulatory framework. They conveniently describe it as too rigid and accuse it of hindering patients’ access to “innovative” treatments. That is why; they showcase AL as the future and reiterate that efficacy -as it costs them far less to demonstrate- should be the key focus. A more “flexible” and “predictable” market access and pricing and reimbursement environment as envisaged and guaranteed by AL opens the doors for their expensive treatments. Here lies one of the keys to better understand AL and its place in the overall debate about medicines in Europe. Industry does not appreciate the polyphony that exists with the different evidence requirements and standards put forward by the various national regulatory authorities. AL offers a way out, as it tries to a) “tie the hands” of Health Technology Assessment (HTA) bodies, payers and national competent authorities by limiting their independence and b) force them to accept greater uncertainty (for more information, please read “Pharma is moving fast: What is coming up in pharmaceuticals in Europe”). Additionally, it touches the sensitive and emotionally charged notion of unmet need and emphasizes the mantra of early and fast access over everything else. It thus leaves no space for discussion around the quality of innovation (access to what?) and eventually prevents an open, healthy and impartial debate on the genuine needs of patients across the spectrum. We cannot afford not to have such a conversation as a lot of the areas where there is unmet medical need today are due to the current market and not public health-driven model of medical innovation. We need to work together to demand real innovation based on public health needs and proven therapeutic advance in comparison to existing medicines.

AL is a highly complex and delicate issue. Let us not forget that up until recently even the Commission’s DG SANCO (now DG SANTE) was very skeptical towards it. There are voices within industry that still express similar doubts. Nevertheless, EFPIA along with the EMA promote it as a flagship initiative. DG SANTE has the oversight of the CHMP/EMA’s decisions and a duty to carefully balance all positions as public health is at stake. As I have previously noted, a shorter time to the market would possibly be beneficial both for the industry as well as for particular categories of patients only as long as sufficient safeguards are in place.

Bundesregierung blockiert grenzüberschreitenden Literaturzugang für blinde und sehbehinderte Menschen


Berlin, 7. Mai 2015 Im Juni 2013 verabschiedete die Weltorganisation für geistiges Eigentum (WIPO) in Marrakesch einen Vertrag, der für blinde, seh- und lesebehinderte Menschen den Zugang zu urheberrechtlich geschützten Werken verbessert. Ziel ist, dass die Blindenbüchereien ihre Bücherbestände künftig auch über Grenzen hinweg austauschen können. Nun blockiert die deutsche Bundesregierung die Ratifizierung des Vertrages.

Im Kern geht es um die Frage, ob die EU den Vertrag ratifiziert oder ob jeder Mitgliedsstaat einzeln ratifizieren muss. In der vergangenen Woche hat die europäische Kommission einen Kompromissvorschlag präsentiert, der die rechtliche Zuständigkeit der Europäischen Union ebenso anerkennt wie die Souveränität der EU-Mitgliedsstaaten, den Marrakesch-Vertrag individuell zu ratifizieren. Wie die Europäische Blindenunion (EBU) berichtet, droht dieser Kompromiss nun an den Regierungen Deutschlands und Italiens zu scheitern.

Dazu EBU-Präsident Wolfgang Angermann: “Der Widerstand der deutschen Regierung hat nichts mit juristischen Formalien zu tun, hier fehlt schlicht und ergreifend der politische Wille, uns zu unserem Recht auf Lesen zu verhelfen. Als blinder Mensch aus Deutschland wie auch als Europäer bin ich zutiefst enttäuscht, dass Deutschland eine Ratifizierung durch die EU ablehnt. Meine dringende Bitte an die deutsche Regierung ist, diese Position zu überdenken und sich in der nächsten Woche im europäischen Rat für eine zügige Ratifizierung durch die EU einzusetzen.“

Hintergrund – Marrakesch Vertrag: Der sogenannte Marrakesch Vertrag erlaubt Blindenorganisationen und Blindenbüchereien auf der ganzen Welt, ihre Bestände an barrierefreier Literatur auszutauschen. So können beispielsweise Spanien und Argentinien ihre Buchbestände, die mehr als 150.000 barrierefreie Werke umfassen, allen lateinamerikanischen Ländern zugänglich machen, sobald die Regierungen der Länder diesen Vertrag ratifizieren und in das jeweilige nationale Urheberrecht überführen.

Hintergrund – Europäische Blindenunion (EBU): Die Europäische Blindenunion, gegründet 1984, ist eine gemeinnützige Nichtregierungsorganisation, deren Ziel es ist die Interessen von blinden und sehbehinderten Menschen in Europa durchzusetzen und zu schützen. Als eine von sechs regionalen Organisationen der Weltblindenunion spielte die EBU eine entscheidende Rolle bei der Erarbeitung und Verabschiedung des Marrakesch Vertrages. Der EBU gehören Organisationen aus 45 europäischen Ländern an, darunter auch der Deutsche Blinden- und Sehbehindertenverband (DBSV).

Wolfgang Angermann
European Blind Union
Fon: +49 173 2857543
Mail: HYPERLINK “mailto:w.angermann@dbsv.org” w.angermann@dbsv.org

I Ciechi espressono disappunto per posizione italiana

Comunicato stampa
Roma, 08/05/2015
L’Unione Italiana dei Ciechi e degli Ipovedenti ONLUS invita i governi di Italia e di Germania a non ostacolare la ratifica da parte dell’UE del nostro Trattato di Marrakech sul diritto alla lettura!
Sono passati quasi due anni dalla firma a Marrakech di un trattato che segna un fondamentale passo in avanti per la realizzazione del pieno accesso ai libri da parte delle persone cieche e ipovedenti. Tuttavia, il governo tedesco e quello italiano, a nostro avviso, si stanno adoperando affinché gli Stati membri dell’Unione europea blocchino la ratifica da parte dell’UE del Trattato di Marrakech. Questa riluttanza non è dovuta tanto a tecnicismi legali, ma quanto alla carente volontà politica di garantire a tutte le persone non vedenti, ipovedenti e con altre disabilità di lettura il pieno accesso al patrimonio librario dell’umanità indipendentemente dai vincoli del diritto d’autore.
Il Presidente dell’Unione Europea dei Ciechi (EBU), Wolfgang Angermann, ha detto:
“Come cittadino tedesco con disabilità visiva e anche come cittadino europeo, sono profondamente deluso dalla riluttanza della Germania ad accettare la ratifica da parte dell’UE di questo trattato. Sollecito il governo tedesco a rivedere le proprie posizioni e a offrire il proprio sostegno a un accordo per la rapida ratifica da parte dell’Unione europea che verrà discusso la prossima settimana durante la riunione del Consiglio dell’Unione europea”.
Il governo tedesco, come scusa per opporsi alla ratifica UE, fa riferimento ad alcune affermazioni false e inconsistenti secondo le quali questo settore non è di esclusiva competenza dell’UE, nonostante sia i servizi giuridici della Commissione sia quelli del Consiglio abbiano insistito sull’evidenza della competenza esclusiva dell’UE, fatto supportato da molteplici giudizi della Corte europea (http://kluwercopyrightblog.com/2015/05/03/blocking-marrakesh-an-argument-based-on-a-house-of-cards/ http://kluwercopyrightblog.com/2015/05/03/blocking-marrakesh-an-argument-based-on-a-house-of-cards/).
Mario Barbuto, Presidente dell’Unione Italiana dei Ciechi e degli Ipovedenti ONLUS, ha espresso il proprio disappunto per la posizione assunta dal governo italiano il quale, ostacolando la ratifica del Trattato di Marrakech, non rispetta i suoi obblighi nei confronti delle persone con disabilità ai sensi dell’art. 30 della Convenzione delle Nazioni Unite sui Diritti delle Persone con Disabilità. “Il nostro governo non trae alcun vantaggio da questa posizione e perde, invece, una grande occasione per porre fine alla “carestia dei libri” assicurando a milioni di persone cieche e ipovedenti in tutto il mondo l’accesso all’educazione, alla cultura e allo svago attraverso la lettura”.
L’Unione Italiana dei Ciechi e degli Ipovedenti ONLUS non riesce a comprendere le ragioni per cui l’Italia, che ha una legislazione particolarmente avanzata riguardo alle eccezioni al diritto d’autore in favore delle persone disabili, abbia assunto in seno al Consiglio dell’Unione europea una posizione chiaramente contrastante con le esigenze delle persone non vedenti in Europa e nel resto del mondo. La scorsa settimana la Commissione europea ha proposto un compromesso che rispetta la sovranità dei singoli Stati membri dell’UE per quanto concerne la ratifica del Trattato di Marrakech pur affermando il principio della competenza giuridica dell’Unione europea. Respingendo questo compromesso, i governi dell’Italia e della Germania hanno dimostrato scarsa flessibilità, al punto da compromettere un possibile accordo.
Se dovesse concretizzarsi il blocco della ratifica del Trattato di Marrakech da parte dell’Unione europea le barriere del diritto d’autore all’accesso alla cultura da parte dei non vedenti continueranno ad esistere ancora per molti anni e i cittadini non vedenti e ipovedenti dovranno attendere che la Corte di giustizia europea esprima il proprio parere (indubbiamente favorevole alla competenza esclusiva dell’UE riguardo alla ratifica) e che l’UE adotti una nuova normativa quadro comunitaria sul diritto d’autore. Questo ritardo, probabilmente di molti anni, non appare né ragionevole né giustificabile.
Invitiamo caldamente il governo italiano a mostrare maggiore sensibilità nei confronti delle esigenze di milioni di persone cieche e ipovedenti e a dare sostegno a una rapida ratifica del Trattato di Marrakech in tutto il mondo.
Altre informazioni sul Trattato di Marrakech
Il punto centrale di questo trattato è un articolo che autorizza le organizzazioni e le biblioteche dei ciechi a condividere le proprie raccolte di titoli accessibili con altre comunità parlanti la stessa lingua in tutto il mondo. Per es. la Spagna e l’Argentina sarebbero in grado di condividere il proprio patrimonio librario accessibile di oltre 150.000 titoli con tutti i paesi dell’America Latina, non appena il governo di ciascun paese beneficiario avrà ratificato e adottato le misure per far entrare in vigore il Trattato. In sintesi, esso stabilisce il quadro giuridico fondamentale per l’adozione di deroghe nazionali in materia di diritto d’autore in quei paesi che ne sono privi e stabilisce un regime per lo scambio transnazionale di libri in formato accessibile.

Commission, Council and Parliament fight over Marrakesh Treaty

Hot debate on right to read Marrakesh Treaty in European Parliament plenary

The heat has been turned up on the EU Council of Member States to reach a solution for ratification of the Marrakesh Treaty for Visually-Impaired persons. Last night´s debate in the European Parliament Plenary Session expressed the strong opinion of the vast majority of our elected representatives in favour of swift ratification and against the procedural excuses being used by the Council.

The European Commission threatened to send the issue of exclusive EU competence to ratify the Treaty to the European Court of Justice while the Latvian Presidency of the Council expressed total opposition to this possibility. The Commission openly and forcefully “regrets” the Council´s rejection of the Commission´s proposals for ratification and insisted that any new legislation to help implementation would never be a “pre-condition” or “pre-requisite” for EU ratification. On the contrary, the Latvian Presidency said that the presentation of new legislation would “facilitate” the adoption of agreements on ratification and accused the Commission of presenting “poor quality” proposals without saying why. The Latvian Council Presidency did not say what legal changes it wanted from the Commission nor what solution there was to the competence issue but instead forcefully stated: “What needs to be done, must be done!”

Most of the 15 MEPs who spoke in the debate expressed their frustration with the Council over the delay in ratification and implementation of the Treaty. Many demanded a concrete time-table for ratification and rejected placing Marrakesh Ratification and implementation within the general copyright debate currently underway in EU institutions.

Spanish conservative MEP Rosa Estarás stated that the Marrakesh Treaty was the 1st application of UN human rights law (Convention on Rights of Disabled Persons) into international copyright law. She called for an immediate solution to permit ratification and for not mixing this issue up with the general copyright debate .

Italian Socialist Gasbarra asked for a time-table for ratification and to give this issue special priority outside the general copyright debate in the EU.

Spanish leftist Vallina insisted that ratification was a question of human rights of disabled persons and to use procedural questions to block it was simply not acceptable. It went against rights guaranteed by the UN Treaty on the Rights of Persons with Disabilities.

Swedish Green Max Andersson asked all parties to stop squabbling and in-fighting and just to reach a solution.

Five Star Italian Laura Ferrara expressed suspicions that the copyright lobby was behind the blocking of the Treaty and insisted that we had to move from words to deeds.

Hungarian conservative Adam Kosa blamed the Commission for not bringing forth new legislation yet.

UK Labour´s Catherine Stihler expressed her dismay that two years later the Council was still deliberating and stalling on an issue mandated by articles in the UN Convention.

Five Star Italian Isabella Adinolfi accused the great “hypocrisy” for being able to rescue banks in record time but only to have excuses when it comes to helping disabled persons. She cited the strong support of the Vatican for the Marrakesh Treaty as the 1st time human rights law is applied in a copyright treaty.

Hungarian conservative Pal Csaky gave some practical examples of how the Treaty could help solve the problems of cross-border shipment of formatted works for the visually-impaired inside the EU.

German socialdemocrat Weidenholzer stated that he did not understand why countries around the world like Argentina and Canada were ratifying and accused the Council of using “cynical, absurd excuses” for delaying ratification. He said it was not acceptable discuss other political disputes on the backs of the weakest, most suffering minorities such as persons with disabilities.

Greek leftist Notis Mories also accused the Council of “hypocrisy” for not giving preference to human rights and for allowing copyright lobbies to dictate policy.

German Pirate Julia Reda asked if the reasons for blocking the Treaty were political since all the legal services in the Commission and the Council consulted agreed the it was EU exclusive competence to ratify the Treaty. She criticized the negative role of Germany in the Council.

The debate ended without any clear conclusions but with greater visibility of the issues and much greater pressure on the Council of Member States to act.

Questions and requests for EP Plenary debate on Marrakesh Treaty




-Will the Council set a timetable for speedy ratification?

-Does the Council agree that a “mixed ratification” would take years, and that such a delay would run contrary to the best interests of blind and partially sighted readers who are missing out on education, instruction and leisure reading in the meantime.

-Will the Council undertake formally now to not suspend the ratification process, and to make ratification an urgent priority?

-Will the Council assure us that the ratification and implementation of the Treaty will not be made part of wider discussions / legislative action on changes to EU copyright law?


1. We are against suspending the process of ratification of the Marrakesh Treaty as proposed by the Latvian Presidency in the Council. We insist that the Council considers a new compromise agreement that permits swift ratification of the Treaty.

2.The Latvian Presidency´s request for new legislation for implementation of the Treaty is being used as an excuse not to ratify. It is not necessary because the right to apply exceptions and limitations to copyright is clearly in EU law in the information Society Directive and in the laws of many EU member states.  This is the opinion of Council and Commission legal services. In any case, further legislation is a separate issue from ratification. 

3.  The EU is showing a lack of political will to solve procedural questions and a lack of sensitivity toward the needs of disabled persons.  The rights of blind and visually-impaired persons are being put off indefinitely with the excuse of long political processes.  This is also the case of the UN Convention on the Rights of Disabled Persons. Eight years after the ratification process began the EU still has not deposited its ratification in the United Nations. 

4.  The European Commission committed itself in 2013, in words of Commissioner Michel Barnier,  not to place Marrakesh Ratification and implementation in the general debate of new copyright legislation in the EU. Will the Commission withhold this public commitment?

5. We reject the blame game for the lack of results toward ratification that the has been going on for nearly two years between the Council and Commission. 

Adapting medicines to the market or to patients’ needs?

By Yannis Natsis, 22 April 2015

One has to analyse the future landscape and challenges that the European pharmaceutical industry is facing to better comprehend the political developments in medicines unfolding at the moment on the EU level. According to the WHO, the part of European medicines in global pharmaceutical sales is steadily decreasing. It is anticipated that by 2016 Europe will account for just 18% of global pharmaceutical spending – down from 24% in 2011 – with emerging markets (including Brazil, China, Mexico and South Africa) anticipated to account for 30% and the United States of America for 31% of market share.

In other words, the pharmaceutical industry is under pressure in Europe but that does not seem to stop them from imposing high prices on their products. As a result, the issue of high prices of medicines has been put on the European agenda for good since 2014 and the Sovaldi crisis. EU countries irrespective of whether they are in crisis or not, wish to lower medicine prices simply because they cannot afford them and they know for a fact that many more expensive products are on their way.

High prices of medicines & the Dutch-Belgian initiative on joint negotiations with pharma: a preliminary evaluation

This is at the core of the recent Belgian-Dutch initiative which seeks to obtain significant price reductions by joining forces in the negotiations with pharmaceutical companies. This initiative is particularly pertinent in light of the upcoming Dutch Presidency of the EU during the first half of 2016. As clarified, they intend to negotiate jointly but not to purchase medicines together. In other words, they want to 1) set a single price together, 2) create a precedent for further EU coordination and 3) use this as a template on how to deal with expensive innovative treatments namely on Hep C, rare diseases and orphan drugs.

It remains to be seen what the reaction of the industry will be but based on what we have seen before, industry is usually “allergic” towards any attempt to establish some sort of a single price or to open up the negotiation process by means of some form of bilateral or multilateral cooperation. The thinking behind this proposal is that industry will be forced to accept lower prices because countries will get together.

But what is the added value of this Belgian-Dutch initiative in comparison to current reality whereby individual member states bargain with pharmaceutical companies in secret and in the end, manage to get lower prices on their own? With Sovaldi, for instance, since its release EU countries reached deals for “as low as” 13.000 euro per treatment per patient down from the initial 60.000 euro price tag. The answer is simple: The Belgians and the Dutch are confident that they will be able to achieve even lower prices than that through joint negotiations. So far, so good but it gets more complicated.

What is the trade-off for industry and how does this fit in its strategy for the future?

Firstly, it guarantees market access for the latest treatments which is a top priority for pharma. Speedy access to medicines via quick market approval and the respective pricing and reimbursement coverage is the main theme in Brussels today heavily promoted by the European Pharmaceutical Association (EFPIA) but also by numerous patient groups. Secondly, it guarantees volume i.e. countries offer more commercial scale to companies in return for lower prices and thirdly and most importantly, companies push the legislator towards a more flexible market access & pricing and reimbursement framework in the EU.

Paradigm shift: from safety to early market access

This is where it gets tricky. The view that prevails in some member states today is that the EU framework on medicines is too rigid and has to become more flexible in line with the latest technological developments. They claim that safety is of utmost concern but stress that “maybe we have gone too far in pushing for safety to the extent that we stifle access to innovation”. This adds to the opinion that there is an overestimation of what can be achieved with regulatory instruments. Additionally, they argue that much of the regulation is old and from their perspective it has become too complex, too detailed and with too much focus on procedures instead of real issues. They stress that it is imperative to strike a new balance between patient safety and quicker access for patients to innovations.

The recent Belgian-Dutch announcement builds on this perceived need for a “new balance” and is only part of the bigger puzzle to gradually redesign the entire model of drug authorization and marketing in Europe. This is evident mostly through the European Medicines Agency (EMA) pilot projects on adaptive pathways (henceforth AL). We have written before that AL seeks to completely change the way we think of drug development and market approval with potentially very negative consequences on public health.

Adaptive pathways & the early access debate

There is an obsession with getting new medicines on to the market without considering if they offer any substantial therapeutic advance in comparison to existing drugs on the market. This is something crucial completely missing from the debate. Patient groups are often misled to believe that new medicines automatically equal better medicines; although, this is repeatedly proven wrong by many independent reviews such as Prescrire and the Cochrane Collaboration. On one hand, it is understandable to a certain extent why patient associations depending on the disease they represent, offer their unconditional support to initiatives such as adaptive pathways. What is worrisome on the other hand is that DG SANTE, what would be the equivalent of the Ministry of Health in the European Commission downplays the importance of adaptive licensing and simply refers to it as a learning process, with low-scale pilot projects launched independently by the EMA. One only has to look at EFPIA´s website to conclude that the adaptive pathways project is by no means a small scale initiative. EFPIA names it as one of the main themes during its upcoming annual conference and describes adaptive pathways as “flexible development and access pathways within the current regulatory framework that balance early patient access, public health and societal benefits”. It explains that “it starts with an early authorisation of a product focused on a well-defined and targeted population with a clear safety and efficacy profile”.

Concerns over adaptive pathways

The question is why AL is required in the first place when there are tested fast-track regulatory mechanisms (conditional marketing, compassionate use and accelerated assessment) already in place that guarantee patients’ timely access to drugs. These instruments provide controlled patient access without having exhaustive evidence available at the time of the introduction but these approvals are subject to further work to substantiate the value of the product once in use. This means that the system already acknowledges the need to live with a limited degree of certainty. Moreover, there is no doubt that the existing early access tools can be further improved. Nonetheless, the aim of AL is to provide even earlier and quicker access to new medicines.

Here is where the problems start. This will require systems capable of responding to outcomes, including negative findings since it is based on accepting even more uncertainty. It must be noted that numerous regulatory systems do not operate in this way and serious adaptations will be required. Most importantly, delisting a new medicine, should it provide little value at the requested price is currently not a widespread option due to political and financial reasons. It is a well-established fact that once a medicine is on the market, it becomes far more difficult to monitor and control it let alone to withdraw it. It would take two incredibly important variables that cannot be taken from granted: a) political will and b) the governance capacity to make it happen. Furthermore, the scope of implementation of the adaptive pathways model is not clear. There are suspicions that once it gains speed it will not only be limited to “unmet medical need”. Besides, there is a lot of debate on what constitutes “unmet medical need”.

But adaptive licensing is not only about quick access. It is something much broader as it is synonymous with the life-span approach to medicines. As explained in my blog entry Pharma is moving fast: What is coming up in pharmaceuticals in Europe, adaptive pathways envisages an alignment of the regulatory environment with the reimbursement criteria so as to enable early approval and most notably coverage of a new product for an initially limited treatment population. These products are usually premium-priced drugs; that explains why healthcare payers are quite cautious. They see it –and rightly so- as another way for industry to get its products on the market and to be reimbursed. Industry has made it clear that they do not appreciate the current pricing and reimbursement system because a) there is a lot of divergence due to national competence, b) it is unpredictable as pricing & reimbursement decisions are mostly political decisions and c) of the increased evidence requirements that HTA organizations or payers put forward as additional gatekeepers. That is why adaptive pathways puts a lot of emphasis on early dialogues, horizon scanning, parallel scientific advice and criteria convergence.

In this whole debate, industry pushes patients to the forefront and encourages them to demand access to the new treatments and of course, to have them reimbursed by health authorities. Patients need to be fully aware of the risks that go with accepting increased “uncertainty” which is an integral element of adaptive licensing. It is hard to believe how patient safety will not be undermined when timetables are squeezed and much less clinical trial data is required. A shorter time to the market would possibly be beneficial both for the industry as well as for the patients only as long as sufficient safeguards are in place. If not, all this could lead to an unacceptable lowering of evidence requirements and higher risks for public health.

Greek Health Minister calls for public interest pharma model


Main speaking points of the Greek Health Minister Mr. Panayotis KOUROUMPLIS at the informal EU Health Ministers’ Council in Riga, Latvia (20-21 April 2015)1

  1. The sustainability of the public health system accessible to all is a shared goal. Therefore, health expenditure should neither be demonized nor be subjected to horizontal cuts without previous consideration.

  2. Over the past years, under the guidance of the Troika, dramatic cuts have been imposed on Greece without any impact assessment. That is why; today, there is a real humanitarian crisis affecting everyone living in the country.

  3. The astronomical cost of new treatments especially for chronic conditions is certainly not viable not only for Greece but for many other EU countries too, whether they are in crisis or not.

  4. In many cases, the cost of new treatments does not reflect real medical innovation but speculation on the part of pharmaceutical companies.

  5. According to the December 2014 Council Conclusions, the market approval and pricing of new medicines should take into account their real added therapeutic value compared to existing options on the market.

  6. Furthermore, he called on member states to consider joint negotiations and procurement of medicines (for example cancer & HIV treatments). In his view, this will have considerable positive effects on the public budget as well as on European citizens’ health.

  7. This debate is timely as the European Commission is considering improvements of the current approval, pricing and reimbursement system. The guiding principle in these discussions should be the respect of the national competence and the guarantee of the integrity and independence of regulatory institutions such as the European Medicines Agency (EMA). To this end, there must be sufficient safeguards in place to make sure that the regulated i.e. major pharmaceutical companies are not in a position to determine the terms of their regulation.

  8. He called on the EU to build on the May 2010 Conclusions which acknowledged the need to dissociate/delink the price of new medicines from the cost of research & development. He reiterated that the EU can help decisively by conducting pilot projects and feasibility studies on the development of alternative models of medical innovation. In his view, this will lead to truly innovative therapies that effectively address the genuine needs of patients and are accessible by all. These studies will offer the opportunity to move away from the current model of medical innovation that favours monopolies and results in unaffordable treatments.

  9. Finally, the EU must guarantee the public return of investment in research & development of new medicines by means of strict conditionality attached to public funds going into medical R&D.

1 Translation from Greek based on speech published at http://www.kouroumplis.gr/mme/article/1207 (accessed 21 April 2015).

Write to your MEP to speak out for EU Marrakesh Treaty Ratification

Dear MEP:

I would like to call your attention to the plenary debate on the ratification of the Marrakesh Treaty that will take place next session in Strasbourg, probably on April 29th. We would like to ask you to request speaking time or to participate through the “catch the eye” procedure to support the EU´s swift ratification of the Marrakesh Treaty. This would back the demands of millions of blind persons and other visually impaired people in favor of the right to access to reading material in accessible formats.

Please find below a short explanation and suggested speaking points for the debate.

Thank you in advance for your support,

European Blind Union

Speaking points for MEPs for Marrakesh Treaty debate in the European Parliament: Please support in plenary the right to read of blind and visually-impaired persons!

The situation:

Since the international agreement reached on the Marrakesh Treaty nearly two years ago it is not acceptable that the EU and its member states have yet to make any progress toward the ratification and implementation of this important international human rights tool for the access to culture of millions of blind and visually impaired persons. . We are deeply concerned and disappointed that due to a lack of consensus building, technical-legal commitment and political will on the part of EU member states time has been unduly wasted.

Why we need the Treaty?

We are suffering a “book famine” because fewer than 5 percent of the books published in Europe are available in a format which is accessible for blind and low vision readers while the books that are available cannot be shared across borders in Europe and the rest of the world where fewer than 1% of the books published are available for visually-impaired persons. This enormous lack of accessible mother tongue and foreign language literature deprives blind and partially sighted people of their right to education, information and social participation. EU ratification of the Marrakesh Treaty will help overcome the existing barriers of national copyright laws in order to facilitate the cross-border flow of specially formatted works for visually-impaired persons.

What the European Blind Union asks for:

The European Blind Union strongly opposes the attempt by the Latvian Council Presidency to suspend the ratification process by the EU of the Marrakesh Treaty. This would greatly delay the effective entry in force of the Treaty and the facilitation of access to culture of millions of blind persons in Europe and around the world.

The European Blind Union rejects any attempt to include the Marrakesh Treaty in the general debate about the future of copyright in the EU. Former Commissioner Michel Barnier committed himself publicly on behalf of the European Commission for Marrakesh ratification not to be mixed up with the EU´s new copyright framework. This Treaty is a specific issue of basic human rights for persons with disabilities that should not be delayed for many years by mixing it up with very different issues.

If the Council is convinced that new legislation is needed for implementation(though Council and Commission legal services now do not agree) the EBU asks the Council to present a written position on the legislative changes it deems necessary to EU legislation so as to avoid unnecessary disagreements and delays in the future. These should be drafted in close consultation with blind person’s representatives and their organizations to assure that the objectives of the Marrakesh Treaty are not weakened or changed in anyway by new EU legislation. Even if legal changes are needed later, the EBU asks the EU and its member states to proceed now to ratify the Treaty.
The EBU calls upon the Commission and the Council to adopt a time table which indicates the time frame for the ratification and implementation of the Marrakech treaty.

The EBU asks the European Parliament, the Commission and the Council to establish three-way informal “trialogue” consultations to reach an agreement on the swiftest way of assuring ratification and implementation of the Treaty.

Marrakesh in the EU: facing the excuses and delay tactics after Council statement

What the Council Statement on Marrakech says:

Council Statement: http://www.statewatch.org/news/2015/apr/eu-council-marrakesh-treaty-guidance-7321-15.pdf

Two separate issues are dealt with: how to put Marrakesh into EU law and how to ratify the Treaty

We are facing two issues put forth by EU Member States: “the appropriate sequence of the implementation of the Marrakesh Treaty” and “the appropriate legal basis for the decision, in conjunction with the question of competence (exclusive versus shared)” Even if there are first legislative changes in copyright law for Marrakesh, it is still not at all clear that EU Member States will want to ratify as exclusive EU competence.

As opposed to the Commission the Council´s position is that the Treaty cannot be implemented without changes in EU legislation. The Council presents no legal arguments for its position while the Commission has. It criticizes the Commission harshly for not presenting a legislative proposal in last year and a half and for presenting “vague proposals that lack legal certainty.” This is a blame game, a political ping-pong that wastes time and diverts attention from ratification.

Surprisingly, the Council admits that it could take the decision to ratify the Treaty now and to deposit the ratification decision in WIPO once “legal implementation” is done (but prefers to have new legislation first): “even if the Council adopts the Decision on the conclusion of the Marrakesh Treaty on behalf of the European Union, it would not be possible to deposit the relevant instruments of ratification (and thus finalise the conclusion of the Marrakesh Treaty by the European Union) until the internal EU legal framework has been adjusted accordingly.”

Competence issue: The Council admits that its own legal service agrees with the Commission that it is “EU exclusive competence” Logically this also means that the Council legal service also implies that there is no need for new legislation since the basis of EU exclusive competence is that it is already covered  by EU law.

The Council says some member states want EU Treaty Article 19.1 (to combat discrimination) to also be used as a legal basis for ratification.

Finally, the Council asks the Commission to suspend the ratification request and asks to Commission to present a legislative proposal to adapt Marrakesh to EU law.
Possible Responses for the debate in the European Parliament Plenary(last week of April):

Express our profound dissatisfaction that over a year and a half time has been lost for access to culture for the visually-impaired due to a lack of consensus building, technical-legal commitment and political will on the part of EU member states. This expresses a lack of sensitivity of the needs of blind and visually impaired persons. We do not want a blame game between Council and Commission but concrete, swift progress toward Treaty ratification.
Demand that the Council presents a written position on the legislative changes it deems necessary to EU legislation so as to avoid unnecessary disagreements and delays in the future. These should be drafted in close consultation with blind persons representatives and their organizations to assure that the objectives of the Marrakesh Treaty are not weakened or changed in anyway by new EU legislation.
Reject the suspension of the Ratification process as proposed by the Council and reject inserting Marrakesh legal implementation in the general copyright debate.
Ask the European Parliament, the Commission and the Council to have three-way informal consultations to reach an agreement on the swiftest way of assuring ratification and implementation.
Demand that the Council and the Commission adopt a timetable for the ratification/implementation process.

NOTE: Please contact your MEPs.  Any member of the European Parliament from any country or political group can participate in this plenary debate. Even if he/she does not have official speaking time, he or she can ask to speak briefly from the floor of the plenary debate by the “catch the eye” process.

Pharma is moving fast: What is coming up in pharmaceuticals in Europe

by Yannis Natsis (17/03/2015)

I recently attended a seminar in Brussels on medical innovation beautifully hosted by an important pharmaceutical company. As always, the setting was ideal. Fancy 5 star hotel, delicious buffet lunch and lots of people working in public relations. The composition of the panel followed the usual recipe successfully tried in corporate events: An esteemed member of the academia, a president of a European patient federation, a classy pharmaceutical executive, an influential certainly pro-business EU public official and an expert. Last but not least, the discussion was moderated by an excellent American facilitator.

As the presentations kicked off, the University professor emphasized the incredible economic significance of the pharmaceutical sector for jobs and growth Europe and reminded everyone that the patent system needs to be defended by all means as this is one of the very few guarantees for innovation. Innovation was underlined by the patient representative too along with repeated and rather emotional calls for patients’ timely access to new treatments in order to meet “unmet” medical needs. The pharmaceutical representative stressed that her sector invests considerable amounts of money in research and development of life-saving treatments. She added that in spite of the very high failure rates, pharma companies do not give up because “human lives are at stake”. The public official agreed and reassured her that her business’ aspirations are taken on board by EU policy-making institutions. Last but not least, the independent expert reaffirmed the need for higher patent protection and stronger enforcement of intellectual property rights as the way forward.

During the Q&A session, the high cost of medicines was briefly touched upon only to be overshadowed by voices claiming that non-treatment costs society more and that patient outcomes should be the guiding criterion in cost-effectiveness assessments. As the icing on the cake, the public official noted that the absence of streamlining of regulatory and reimbursement requirements leads to higher costs for drug development and consequently to higher end prices. The patient representative along with people from the audience reiterated the necessity to institutionalize the early dialogue between all stakeholders, increase public funding and expedite access to new treatments. Accessibility” of medicines was another highlight of the day seen under the prism of “innovative” methods of bringing drugs to European citizens through adaptive licensing, differentiated pricing, prolonged payment of curative treatments and a more active role of patients in the authorization procedure of new medicinal products.

The meeting came to a close and I felt puzzled. “Early dialogue”, “speedy access to new treatments”, “patient outcomes”, “innovation saves lives”, “innovative payment methods”, “streamlining of regulatory requirements” were all familiar themes and at the end of the day, they make sense and do sound nice. It struck me however that new battlegrounds are appearing as pro-industry lobbies work proactively to guide future European legislation. On the EU level, there is a consistent effort to review and eventually redesign the drug development pathway from discovery to product launch and post authorization monitoring to make industry’s life easier to the detriment of public interest. To this end, the pharmaceutical industry is shaping the agenda by choosing its facts and promoting a language that is easily owned by everyone. Let’s examine some of this rhetoric but from a different perspective, that of thinking of health in terms of a public good and not merely a business.

Early dialogue of all stakeholders (regulators, payers, European Medicines Agency-EMA, Health Technology Assesment-HTA bodies): as there are multiple levels of competences and evaluation criteria split between the EU and the member states during the different phases of drug development, industry wants to guarantee that it has a decisive say in the process early on. They want a detailed overview and a reserved place around the table during the market approval phase and the very important pricing and reimbursement stage. Adaptive licensing & parallel scientific advice are two of the main EU initiatives in this direction.

Early and “speedy” access to medicines: this is the prevailing theme in the EU legislative bodies at the moment. The Council is currently reviewing the existing mechanisms of early access such as conditional approval, compassionate use, and approval under exceptional circumstances. The risks are that very expensive medicines will enter the market faster on fewer reliable clinical trial data and a higher chance of unforeseen adverse effects.

Convergence of evidence requirements: in the spirit of “early dialogues”, industry pushes for a convergence of criteria in relation to market approval, the health technology assessment and the reimbursement phase employed by the different organisations in charge of these stages. Moreover, they highlight the primacy of the European Medicines Agency (EMA) as they do not wish to face additional hurdles from national regulatory authorities. This way they can predict what is coming up and how to tailor the different evaluation stages to their capacity.

Pricing & reimbursement decisions: this is probably the most important stage as it determines patients’ access to a treatment. Market approval is (or at least should be) based on scientific criteria in order to evaluate the efficacy, quality and safety of a drug. This makes it de facto more predictable i.e. more manageable. On the contrary, pricing & reimbursement is and has always been a political decision based on a different set of criteria.

HTA bodies: these are crucial for evaluating the added therapeutic value of new medicines. Therefore, HTA bodies are increasingly regarded as gatekeepers against the flood of me-too medicines that offer modest or no real therapeutic value but usually cost a fortune to public health systems in Europe and beyond. The more HTA’s role grows as part of the regulatory framework, the more they are targeted by pharma. This is due to the HTA’s distinct and instrumental role in introducing the concept of “therapeutic added value” into the market authorization procedure. This concept signals a higher threshold for the entry of new truly innovative medicines. The EMA –whose independence and capacity to control conflicts of interest are doubtful- is currently running pilot projects on adaptive licensing and parallel scientific advice that may a) threaten HTA bodies’ independence, b) weaken the regulatory framework, and c) lower safeguards.

Cost-effective, synergies between all stakeholders: emphasis is placed on cost-effectiveness against cost-benefit analyses. Moreover, industry and the EMA’s pilot projects aim to redesign the traditional licensing path with a view to putting their products earlier on the market while relying on fewer clinical data. It is worrisome that the language used in adaptive pathways (initially named adaptive licensing) widens the scope for the entry of new medicines referring to all medicines and not only those to treat unmet medical needs.

Views on early access vary considerably among EU member states as there are economic concerns especially for those where full reimbursement of treatments is foreseen. That is why, when it comes to HTA, they favour closer cooperation but wish to keep the final assessment on the added value strictly on a national level and oppose any efforts towards a single European HTA. In the meantime, the European Commission has announced that it will conduct a study to compare how member states implement the various early-access schemes-they want to make sure that there is no market distortion, referring to off-label use. The role of patient associations in this debate cannot be overlooked. They are often encouraged by pharmaceutical companies to put pressure on governments to demand early access to treatments as is the case with the seemingly private Dutch initiative presented via mytomorrows.com which is heavily propagated in the Council by the Netherlands.

There may be no new attention-grabbing legislation coming up but all of these initiatives and pilot projects need to be closely monitored as they influence ongoing debate and most importantly future legislation. On the whole, should pharma’s strategy be successful, it will result in an ever closer incestuous cooperation between the regulator and the regulated where any independent scrutiny of new medicines and their prices could be seriously weakened.