Market access in Italy: Reforms at AIFA

Clare Foy (Director – Global Market Access, Mtech Access) speaks to Italian market access expert Prof. Fabrizio Gianfrate (Professor of Health Economics and Outcomes Research [HEOR] and Ex-Payer) about the market access landscape in Italy, particularly regarding changes at the Agenzia Italiana del Farmaco (AIFA).

We explore:
- The nature of the Italian market and the reimbursement process
- Pricing and market access considerations when launching in Italy
- What the reforms at AIFA mean for market access and managed entry agreements
- How the AIFA changes specifically impact innovative products
- Changes to early access programmes in Italy
- Impact of these changes on international pricing, particularly with the introduction of the EU Joint Clinical Assessment (JCA)

This episode was first broadcast as a live webinar in October 2023. Learn more at: https://mtechaccess.co.uk/italy-market-access-aifa-reforms/

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Transcript

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- Welcome to this Mtech Access webinar. At Mtech Access, we provide health economics and outcomes research and market access services from strategy through to implementation. Get in touch today to discuss your market access goals. First, though, I hope you enjoy the webinar. Welcome, everyone. Thanks for joining our latest Global Whispers webinar. Please see our YouTube channel for past webinars, and look out for more content from us in the future. Today's topic is Market Access in Italy. I'm Clare Foy, Director of Global Market Access at Mtech Access. We have a great mix of audience today across industry and healthcare systems. I'd like to particularly welcome our global affiliate partners who play a key role in the work that we do. For those of you that don't know us very well, Mtech Access is a global specialist, health economics outcomes and market access consultancy. With a track record in expert delivery, we provide specialist support to pharmaceutical and Medtech clients, and work as a collaborative partner to health systems worldwide. Today we're focusing on market access challenges in Italy, and I'm delighted to welcome our guest, Fabrizio Gianfrate. Welcome, Fabrizio, thank you for joining us. Please, could you take a moment to introduce yourself and your experience.- Thank you very much, Clare. Thanks for the invitation. Hello, everybody. I am Fabrizio Gianfrate. I am a health economist by training. I am full professor of Health Economics in Italy, to Italian universities and business schools. I have been a payer in AIFA for some years, and at regional level in some regional technology assessment committees. And before I served a couple of years as Director of the Italian Ministry of Health. Happy to be here and ready to answer your good questions.- Thanks, Fabrizio. So your area of expertise is obviously market access in Italy. I know there are some big changes happening or about to happen in Italy at the moment. But if you could start by giving us a brief outline of the nature of the market currently in terms of the key stakeholder bodies, reimbursement processes for both MedTech and pharma, please.- Well, we have, you know, a national healthcare service, a unique public insurance covering also the pharmaceutical spending. So all citizens are covered by the national insurers, by the National Health Service, and including the drugs. The owner of the process for market access in Italy is the Italian Drug Agency, the government agency for drugs, AIFA, the name is Agenzia Italiana del Farmaco, which is the body responsible, between other responsibilities, to evaluate a new product or a new indication, and to negotiate with the manufacturer the level of price and the reimbursement conditions, including restrictions, or whenever possible or needed, manage the agreements, both financial basis or outcome basis.- Perfect, thank you.- Sorry, one to discuss is which are the criteria for leading a change in the AIFA organisation process, and which are the unmet needs in the system needing those changes, leading to those changes. We have two main weaknesses between many point of strength. One weakness is the duration of the negotiation, which is longer than the other European countries, taking from the EMA approval to the publication on Gazzetta Ufficiale, which is the official definition of the reimbursement and the price. From the EMA approval to Gazzetta Ufficiale, the average time is 18 months, which is quite long, in any case, longer than some other big European countries. The other point of weakness to amend, to change, to improve is the level of spending, which is a common problem. The level of spending, which is in Italy every year since many years beyond, above the planned budget. So there is an exceeding of the spending, even 20% on the planned budget. And this is something to be amended, to be solved, to be minimised or mitigated.- That's really helpful background, thank you. And if you could just explain a bit about the committees within AIFA, the CTS and the CPR, and how the process works currently. And then we'll come onto the changes in the new CSE, which is going to be enforced soon.- Yeah, the current process and the related organisation is in two different steps. Once the manufacturer present the pricing reimbursement dossier, the product is evaluated from an health technology assessment perspective by the technical committee. Technical committee, CTS,(Commissione Tecnico-Scientifica), has the responsibility to evaluate the clinical value better, the added clinical value compared with the standard of care, and giving the deliverable of the technical committee is to give a recommendation for the reimbursement. So the outcome of the technical committee is to recommend the reimbursement and the specific placing therapy. Once this kind of deliverable has been given, the floor goes to the pricing reimbursement committee, which is the committee defining the reimbursement, the restrictions, the level of reimbursement, including the restrictions, and the level of price negotiated with the company. So the big difference between CTS and CPR is that in CPR, in the pricing reimbursement committee, the manufacturer is called to attend the process to negotiate the level of price and the reimbursement level or restrictions whenever needed. Once the agreement has been reached, the agreement about the level of price and the reimbursement conditions, the product, the reimbursement and the price conditions are published, not entirely, but the main informations are published on the Gazzetta Ufficiale, which is the government. The government balloting the publication, the Gazzetta Ufficiale, is the official step for defining that product in charge to the public health, included in the positive list of the formulary at the national level.- Thank you. And you explained earlier that there are some changes planned, partly to speed up access and partly to save costs. If you could just outline for us the changes that are being planned or proposed at the moment. I understand they haven't quite come into force yet, but what we do know about it, I'm sure everyone will be interested to hear the latest.- Yeah, sure. I mean, the most recent decision was to prolong the current CTS and CPR. So to delay again the, the statement, the starting of the activity of the new unified committee until the 1st of December. So the 1st of December, the new committee, unified committee should be in place starting to work, which are the main differences between the previous two committees and the new unified committee. Only one place, only one chamber, only one table, or a technology assessment and pricing and reimbursement, which is the expected advantage or advantages, not to have a back and forth of the pricing reimbursement dossier between the two previous committees. When, for instance, when one product was negotiated for a price and some restrictions were proposed, the clinical consequences of those restrictions had to be evaluated by the technical committee. So the pricing reimbursement dossier, the dossier in the pricing reimbursement committee was again placed back to the committee, to the technical committee, in order to reevaluate or to evaluate the restrictions from the clinical side. Then this price, this price reimbursement dossier will go back again to the pricing reimbursement dossier, to the pricing reimbursement committee. So a back and forth wasting time, requiring prolonging in the end the entire duration of the process. Having all of those activities on the same table, in the same chamber, the objective is to speed up those processes, avoiding some, I mean, wasted time or delay in that. A couple of observation about some caveat or some concern I have about that, it is true that putting together the two committees and managing the dossier in only one table is a way for simplifying the process and speeding up the activities. But one of the problem is that CTS has 10 members, CPR, 10 members. So a total number of 20 experts, committees members, are in place today with the old organisation. The new committee will have 10 members. So the number of experts, the number of members will be halved. My concern is in order to speed up the process, I don't know how it is worth halving the expert, doubling the workload for each of them. So you should take in consideration that those experts

are external experts continuing their job: 11:29

academics, I mean, regional experts. So they have to continue their job. So it is not possible to ask them doubling their engagement with AIFA. So having the objective to speeding up a process, halving the people working on that may be some, I have some concern about that. Other changes are in the governance of AIFA because the general manager role will disappear. General manager was the owner of all processes. President was more representative before, while in the next organisation, general manager will disappear, president will become an executive president. The new scientific director, a new role of director will be established, having the responsibility for managing all the scientific issues of the agency. And an administrative director will be also established in order to manage all the issues related to human resources and all the financial part of the management, not something related directly to the evaluation of the products, to the pricing reimbursement. This is a general picture. So far we do not have any kind of indication about the change in the processes. So my personal opinion is the processes will remain the same, but managed in that new organisation, in that different new organisation with all the pros and cons I tried to explain.- Thank you. That's really helpful. And you pointed out that the number of members in the new CSE will be 10 as opposed to 10 each in CTS and CPR. And as I understand it, the regional representatives will be fewer as well in the CSE. Is that something that you think might have a bearing on the future processes?- This is a very, very good question, because together with the change in the organisation, unifying the merging, pulling together the two committees, there will be a different governance in the end about AIFA or the AIFA. Because the board members, and above all the committees in the future, the committee, the commission members will be appointed differently than before. While so far the regions had the responsibility to appoint 40, more or less, 40% of the members, they will be reduced. Their role will be reduced to appoint only 10, 15% of the members. So the Ministry of Health at the central level, the national level, will be much more empowered in appointing its representatives in AIFA. And while the regions will lose power in that, there is a different, let me say strategic view in the AIFA role, roles, giving more empowerment to the Ministry of Health to the national level instead of the previous regional involvement so far applied. The same, I mentioned at above all the commissions or the new commission compared with the old committees and commission, the same different empowerment will be for the board. The board has the responsibility to ratify, to approve what has been decided by the committee, today, by the pricing reimbursement committee, which is the second step of the process. But as well as the committees, the commission, the new commission, the board will be appointed mainly by the Ministry of Health. So regions will lose a little bit of power because the number of representatives will be lower than before.- That's a very good point. So what sort of impact do you think that would have on pricing strategy, reimbursement, decision-making in Italy? Would companies expect to have to adapt their approach to achieving reimbursement in Italy? What would you recommend, do you think?- Yes, I forget one important aspect in the appointment. And I go to your to your question, to answer your question. Ministry of Economics, Ministry of Treasure is allowed to appoint one member of the commission and of the board. What does it mean? Simply to understand, simply to understand the Ministry of Economics will play a more important role in the decisions by AIFA. And this is strictly related to the spending and to the definition of the price and the reimbursement for a new product, especially those products, more costly, we are going to have a wave of gene therapies and TMPs, combinations of monoclonal antibodies. So more costly treatments in charge to the public health, to the government. And the decision was to formally include Ministry of Economics, Ministry of Treasure in the AIFA governance. In that purpose, pharmaceuticals, pharmaceutical companies, manufacturers will continue to work business as usual, but taking consideration, it will be, in my opinion, harder and harder to obtain the same level of price reimbursement conditions showing the same added value, clinical added value shown so far. So in order to have the same level of reward, I guess it will be more difficult. It will be requested more data, more supporting data will be requested in order to have the same level of price and reimbursement. Or vice versa, in order to have the same price, you have to show better data, or with the same data than today you can have a lower price.- Thank you. That's really clear. I think you're probably right about that. One of the other goals that you said of this new committee was to reduce the time required to assess new drugs. You noted that there are now fewer committee members, so potentially their workload will double. Do you think that we will see that market access is granted sooner in Italy, or do you think that might not be the case?- I am not very optimistic for that. Not only because of the double workload of the single new 10 members halved, considering the 20 members before, but because becoming more and more difficult to find an agreement about the price and reimbursement. This is a problem taking time, considering we base the pricing reimbursement on a negotiation between the company, the manufacturer, and the committee. Negotiation, when difficult, needs time; needs time because I propose a specific price of reimbursement condition, the counterparty says,"No, I do not agree." We have to check other possibility. In the meantime, the time of this meeting has been expired, so we have to rediscuss the next meeting next month. This is the reason why it's needed today, 18 months, because nothing changed in 18 months in terms of value of the product or economic conditions.- Okay, interesting.- A suggestion for the companies, for the manufacturer is it is quite trivial. But to make more effort to be competitive in the market process. So providing proposals, to be proactive in putting on the table proposals for reaching an agreement about the price level and the reimbursement conditions, models and real-world evidence. And indirect comparison in Italy are very important and so on.- Okay. You've set up my next question really nicely there.'Cause I suppose one of the things that companies can do is put forward managed entry agreements and different innovative ways of pricing products that perhaps make it more appetising. Is that something that you expect might change in the future in Italy, or do you think we'll see this, you know, the same sort of view on those sorts of innovative methodologies?- You know, Italy has been in the last years, last 20 years, 18 years, the country reimbursing the highest number of products maybe in the world, including managed entry agreements, outcome-based. So payment by result, risk sharing, cost sharing, (indistinct). This was until four or five years ago when the AIFA management at that time decided no longer to adopt those agreements for many reasons. I mean, including some political reasons. I would not explain, I would not discuss about that. Sorry. I guess the need to find an agreement for the more costly incoming therapies and drugs, combination gene therapies and so on, will make the decision-makers to take, again, in consideration the adoption of outcome-based agreement schemes which are adopted now in Italy for ATMPs. The example is (indistinct), payment at result, meaning, you know, instalments. But each instalment is paid all if the patient is still a responder. So it is a mix between a financial agreement, and it is an instalments and outcome-based because paid only if the patient is still a responder. I guess for gene therapies, ATMPs, this scheme will be adopted more frequently in the future in order to make possible an agreement in the end, the reimbursement of the product. But similar schemes will be readopted for monoclonal antibodies, for traditional, I mean, therapies, especially in combination where the cost is in many cases doubling compared with the monotherapy. So I guess in the future the companies should be ready to come back to talk with AIFA, also considering the possibility to be on board with an outcome-based agreement with payment by result. On the other end, we have the infrastructure already in place, because the web platform put in place by AIFA years ago is a very good tool for managing those kinds of agreement. And it is available, so it is only a matter of goodwill to readopt those kinds of outcome-based agreements.- Okay, and just focusing on innovative products, so things like advanced therapy products, gene therapy, cell therapies as you mentioned, what do you think all these changes mean for the future of those products? And also, if you could perhaps comment on the future of the innovation fund.- But the new government said that the innovative fund, so the innovative status evaluation linked to the innovative fund, but innovative products fund will be confirmed. It has been confirmed. So there is a clear statement continuing to reward the products considered, evaluated innovative, granted of the innovative status by by AIFA. There is also an increasing fund. The fund is increased, not in a dramatic way, but there are more money for innovative products. At the beginning, the the extra budget was 1 billion. Now it is 1.3 billions, if I remember well. So there is the knowledge, the fact to reward innovation is something recognised as a good strategy from the Italian authorities confirmed. So for the manufacturer, that means to have this opportunity, it is not mandatory. The evaluation of the innovative status in Italy is not mandatory. So it is up to the company to decide, to ask or not for the evaluation. The effort from the company asking the innovative status is to consider also this possibility and to show those data to satisfy the three criteria for the evaluation of the innovative status, unmet need that added clinical value and quality of evidence.- Perfect, thank you. And thinking also about patient access to drugs and timely access, I believe there are some changes to the early access programmes available in Italy. Could you talk us through those changes as well?- We have two programmes for the early access. The main one is called 648. It is called by a number because it is the number of the decree, of the low, establishing the use for this early access. It is for those products having no alternative options for those patients. In most cases, not yet approved by EMA or even better, far from the EMA approval having only preliminary data from phase 2. But because of the high level of unmet needs, AIFA decide to make available and reimburse those products. There is a restriction in the 648 inclusion because of the cost, because it is a reimbursement at the manufacturer price, even if to be accepted by AIFA, it is not very clear because it is not a negotiation with AIFA about the price of 648, but the price has to be accepted by AIFA. And there is a restriction because of the financial burden. In the future, I guess it will be an opportunity only for a few products where there is really a high level of unmet needs, orphan, some ultra-orphan indications, or some pathologies where the life-threatening condition is particularly high, but where the quality of the clinical data are sufficient to be considered a real opportunity for those patients. So low number of patients entering the 648 showing real good clinical benefit for those patients. The other programme is called 326. It is over 5% funded because it is not funded by the public health, by the national care service, by that small budget in charge to AIFA coming from the contributions of the manufacturers of the pharmaceutical. Each pharmaceutical company should give 5% from marketing and sales spending to AIFA. It is a sort of taxation in order to provide this fund, which AIFA uses for 326. I mean, we are talking about 30 millions, so peanuts compare with, I mean, 24 or 25 billions of the pharmaceutical budget. 326 is going to disappear or to be very limited to those products not available in Europe, to be imported from other geographic areas. Or where really the ultra-orphan condition is established.- Some big changes coming up then. So all these changes, how do you think that will impact on strategy from pharmaceutical companies to achieve the price they want and the access they want for patients in Italy? What sort of advice would you give to companies embarking on that journey?- Well, I don't see big changes in the requirement from the new AIFA to the companies to provide new data or different strategies or different approaches. What I see is more a quantitative than a qualitative change. So the same data, the same supporting data or value propositions will be provided, will be asked to be provided by the companies, but at a higher level, at a higher level of quality. So the competition in my opinion in the new AIFA will be about the quality of the data. I'm talking about the clinical data and the economic data as well, but maintaining the same processes, the same requirement. So maybe a bit more quality of life data will be requested, simply because, you know, we are quite, not very considering in the past, quality of life evidence, repeatedly on the opposite side of the GBA or the UK NICE. I guess quality of life will play a more important role in the future. But apart from that, I believe the same kind of data will be requested to the companies, more and more qualitatively high level. So high level of quality of those data in the clinical and in the economic side.- And what about the ability of companies to engage with AIFA? You mentioned there was obviously a negotiation process previously between companies in the CPR. Are we expecting a similar sort of negotiation process with the CSE? Will that be done in one stage or multiple stages? Do you know, do you have any clarity on that at the moment?- I don't think so. I am quite pessimistic about that, because despite recently AIFA people which are expiring their role, issued, I mean, also add a meeting, an open meeting, an open session, and issuing a document, a statement opening the AIFA to the stakeholders. But they clearly specified that this open ship is not related to a single product. Or to have a sort of a sort of, what I can say scientific advice for a single product, differently than other agencies in other countries. I do not believe someone in AIFA will take the responsibility to talk with the company before the company moves officially a request of the pricing reimbursement. Because there are precedents many years ago, to be honest, of corruption, bribes, and not transparent, I mean, behaviours. And this will be really a damage for the agency. So I am quite pessimistic. I guess companies will not have the opportunity to talk with the agency before starting officially a request of pricing reimbursement.- Okay, that's interesting.- At least talking early with the company about that product, because it is possible to have a meeting in order to discuss about the strategy of the company to invest in Italy instead of having a programme of collaborations with the academic world, with universities. But if you want to talk with AIFA a about your product before the product has been started officially in an evaluation with AIFA presenting the pricing reimbursement dossier, this is in my opinion, are not coming and not possible, even in the future.- Okay, thank you. That's interesting. I know some HTA bodies are going the other way and encouraging more engagement, but I can see your point there and the fears about corruption and so on. So that's quite an interesting take on it. What impact do you think the changes that are going on in Italy could have outside Italy, in Europe, and in the world? I'm also thinking, mindful of the fact that the joint clinical assessment will start to take place in the next couple of years, do you think some of these changes might have a bearing on any of that?- Well, I think it is a big opportunity. I am in favour of that. Because similar to what happened at establishing EMA, centralising the clinical assessment, I guess with all the differences, of course, I guess the same benefit can come having a joint clinical assessment at European level. The problem is the resistance to change at the local level, because the first objection I received talking with the people having roles in AIFA was, oh, but if someone else get our job at the European level, we lose our role or roles or part of our roles. So I risk to lose my job. Sorry to be trivial, but it is only an example to say which are the resistance to change when someone is asked to take your role or to taking the responsibility of some parts of your job. So in order to be successful, a joint clinical assessment should be pursued, should be perceived convenient for AIFA or for the other agencies. So I take the job already done by others. If this is something I can save money, I can save time, and I can have at least the same level of quality instead of I do my job, I do by myself the job. So those are in my opinion the three conditions to have a successful, accepted, successfully accepted joint clinical assessment. Otherwise it will remain something nice to have. Okay, there is the joint clinical assessment, but we do our job as usual considering which is our experience and our processes. I have seen some agencies in big countries, GBA and France seemed to have this kind of approach. Okay, very happy to have joint clinical assessment. We will be very happy to evaluate your job, but we will continue our procedures following our processes.- Yeah, I think it remains to be seen how will that all affect things and how those assessments will be made. We've talked quite a lot about the national level and AIFA, are there any changes or any impacts that you think we would see in regional market access in Italy? Perhaps you could talk a bit about the HTA that is done regionally in the country.- But there are no proposals to change the empowerment of the low empowerment, the low-level empowerment of the regions for pharmaceuticals. They play the real important role for biosimilars, for generics, because they are responsible for launching tenders. So the real role of the regions and the manufacturer should work, will work, are working about that is able for tendering, in managing the tenders for biosimilars and generics. Because for patented drugs, regions cannot change the price, cannot change the reimbursement conditions. Theoretically, they can enlarge the reimbursement, paying the difference. But most of the regions have financial problems. So no money for enlarging the indications, enlarging the reimbursement, with the exception of some vaccinations, HPV or pneumococcal. But apart from those exceptions, regions follow the EMA-approved, the AIFA (indistinct), and not empowered to change the price level of the reimbursement conditions.- Thank you. That's been really informative. Are there any other points that you'd like to make, or perhaps a summary of the things that you've talked about and the things that companies need to consider in their strategies for market access in Europe and particularly in Italy.- But new models, a new value-based contract or managed entry agreements, models. I guess in order to make available the reimbursement, to make possible the reimbursement available, those products for patients, costly ATMPs or combinations or even new products more costly than today will require to be managed by creative, let me say, agreements or contracts. We have seen some examples not in Italy, in other countries, you know better than me. Subscription models instead of value-based contract on the patient population outcome. Or I mean, again, creativity from the companies would be a winning competitive factor in my opinion for the future.- Yeah, I think that's a great point. We're certainly seeing that in other countries, as you say, and some of our clients are coming up with some really great creative ideas with our support. So yes, that's something definitely to watch out for in the future. Thank you so much, Fabrizio. I think that's been very, very helpful. Good to talk about some of the changes that are happening, and also just a general overview of the marketplace. So we thank you very much for your time. That was great. And thank you to the audience as well for listening. We hope you found that useful. We'll follow up to answer any of the questions that we didn't have time to cover today. And we'll be happy to continue talking to you and providing support if there is anything that you would like. And just one final thing to mention. ISPOR is coming up, the European ISPOR in Copenhagen next month. We will be there and we hope you'll be there too, and we'd love to meet you. So please do get in touch and arrange a meeting. Thank you, everyone. Thank you for watching. If you'd like to find out more about our work or how we could support your market access goals, please email info@mtechaccess.co.uk, or visit our website at mtechaccess.co.uk.