Designing a Global Market Access Strategy Built for MFN

How will Most Favored Nation (MFN) pricing reshape global pharmaceutical strategy? What do emerging Centers for Medicare & Medicaid Service (CMS) models such as GENEROUS, GLOBE, and GUARD mean for launch planning, pricing corridors, and payer expectations worldwide? How should global market access teams prepare for a more transparent and tightly connected pricing environment?

MFN reform is already influencing how companies plan, price, and launch medicines around the world. While CMS proposals sit at the center of the debate, the implications extend far beyond the US. The increased transparency required in models under consideration has the potential to accelerate global price convergence, affect international reference dynamics, and place new pressures on evidence generation, launch sequencing, and global pricing corridors.

This episode was first broadcast as a live webinar on Wednesday 15th April 2026. It is designed to help global and US teams understand and anticipate the worldwide strategic implications of MFN policy. 

The session brought together four experts offering global and US perspectives on MFN:

• Steve O’Malley (President, Petauri Advisors): Moderator and contributor on US access and strategic implications
• Catherine Beecher (Director – Global Pricing and Market Access, Petauri Evidence): Bringing insight into global evidence requirements, lifecycle planning, and cross‑market pricing pressures
• Clare Foy (Director – Global Pricing and Market Access, Petauri Evidence): Bringing expertise in global pricing strategy and launch planning across international markets
• Michael Garner (Vice President, Artia Solutions – Powered by Petauri): Bringing US Medicaid expertise with a focus on CMS MFN proposals and their operational and strategic implications

Learn more at: https://petauri.com/insights/global-market-access-strategy-for-mfn/

In this webinar, we explored:

• The most recent CMS MFN policy developments and how models such as GENEROUS, GLOBE, and GUARD may evolve
• The possible effects of the recent announcement of new tariffs on pharmaceutical manufacturers
• How greater price transparency could affect international pricing corridors and global revenue forecasts
• Impacts on launched products, peri-launch assets, and early pipeline programs from both a global and US policy standpoint
• Strategic options for optimizing ex-US price potential, including evidence generation, innovative agreements, conditional reimbursement, and launch sequencing
• How global market access teams can build pricing and access strategies that remain resilient as MFN models evolve
• Wider policy developments to monitor outside the US, including proposed changes to the exclusivity period in the EU, and the growing influence of the Joint Clinical Assessment

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Transcript

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- Hi, welcome. My name is Steve O'Malley. I'll be the moderator today for our session entitled, Designing a Global Market Access Strategy Built for MFN. Today's session is really meant to give a high level 10,000 foot view of US and global impact of MFN, mostly focused on global. How did this strategy come to be with most favored nation? What does that look like for implications for countries around the globe? We'll be talking a little bit about how this may impact upcoming launches for biotech and mature pharmaceutical companies, as well as products that are already in the market. And then, we'll be thinking through strategic options for companies through our panellists that are listed here today. And then lastly, what are the unintended, or intended complications of most favored nation. Join here today by our panellists, Michael Garner, Catherine Beecher, and Clare Foy, who will introduce themselves here in just a second. But I wanted to thank them and welcome to the discussion and they'll be driving most of the discussion today. So, principally, the most favored nation legislation, if you will, seems pretty straightforward. How do we reduce drug prices in the US based off of referencing other markets? Seems pretty straightforward. Like most laws, there's many unintended consequences when you actually start thinking through actually how it's calculated in the transparency or lack thereof of most favored nation or actually drug pricing. So, we wanted to actually chat about that today, and ultimately, what pharmaceutical manufacturers may think about as they kind of move forward. So, I guess I will start with Michael. Could you really briefly introduce yourself, give us a little bit of your background, and then maybe talk to us a little bit about GENEROUS as part of the MFN, and where you see that heading.- Sure, thank you, Steve. My name is Michael Garner, I'm the vice president of Policy and Strategy for Artia Solutions- Powered by Petauri. And my background, I've been in health policy for close to 35 years, and have primarily been working in the Medicaid markets, although I also have experience in the commercial markets and Medicare as well. So, been following this since its very beginning all the way back to the first Trump administration, and have just a lot of information that I'm really looking forward to share with the group today. GENEROUS, Steve, you're asking, where is GENEROUS going? And that is really the million dollar question, because there's so much uncertainty around it. What we have right now is a model where manufacturers are having to apply to the Federal Centres for Medicaid and Medicare Services, CMI Centre, to say that they want to participate. They've got to provide quite a bit of information to the federal government in order to be considered on whether or not they can join it. And then, they have to ultimately sign a participation agreement with the federal government. Then at some point, the states have to get involved. The states are going to have to make a decision on whether or not they want to join. And even when they want to join, they're going to have to make decision on which drugs they want to use as part of their Medicaid programme that uses the GENEROUS model MFN priced drugs. So, there's a lot going on out there. We still have not heard exactly how many manufacturers are going to ultimately participate. They're supposed to get their applications in by the end of this month, and then they have to have their participation agreements done by the end of June. And then, the states ultimately have to get their applications in to participate by July, and their participation agreements with the federal government by the end of August. So, we've got a lot of time here that we're still looking at, but it's really closing in for the manufacturers at this point to decide whether or not they are going to ultimately sit down and negotiate, and become part of the model. So, that's kind of a general framework, but happy to answer any other questions on that.- Great. I have a tonne of questions for you, so we'll come back to it in a second, but I want to introduce our other panellists as well. Catherine, could you introduce yourself real quick, and then maybe talk a little bit about some of the other programmes within MFN with GUARD and GLOBE?- Absolutely. And thank you, Steve. Thank you, Michael. Hi, everyone, I'm Catherine Beecher. I'm a director in the Global Pricing and Market Access team here at Petauri. And I think Michael's been extremely modest,'cause I think he and his team are supporting companies at the moment, and we're working alongside him to help people assess the ins and outs, and the intricacies of whether to submit for generalists. I think that is a really critical thing. And from the global side, the key piece is, that they're exploring at net level, or at least ostensibly being asked to consider the true net level in these target markets. And there are eight key markets for GENEROUS. And so, we are thinking about how that is going to influence the prices within the US, because obviously, for already marketed products, which is obviously what we're focusing on primarily right now, there is a limited ability, I would say, to make adjustments, ex-US. I think obviously there are some notable exceptions to that. I think we are seeing some public announcements around perhaps some price increases for certain products where that is possible, maybe more in the private sector. We're also seeing some withdrawals as well, obviously companies taking a decision to try, and eliminate risk for smaller, lower price markets, and kind of narrow that global corridor. But ultimately, for the in-market products, there is going to be an adjustment in the US price,'cause we are still seeing a big differential, are we not, Michael, even including all the rebating that's going on. These incremental rebates would need to be applied to get down to ex-manufacturer levels in the ex-US markets.- Yeah, and Cathy, actually, and really again, when we start looking at states and how they're going to react, and also the PBMs and some of the purchasing pools and how they're going to act, there's a real big question about is MFN going to ultimately, what roles they going to play, are states going to sit there? Is there an incentive for states to actually say, now that I know what the MFN price is, I'm going to talk to the manufacturer separately, and say, can you do better? You had consortium PBMs, they're going to have to say, we got to keep adding value. Are they going to come back and say, we know what the MFN is? And so, manufacturers, we want you. So, that uncertainty that you're talking about, where's that bottom price going to ultimately be is a real question mark that we're all trying to figure out.- Yeah, and I think that the key is as well for GENEROUS, obviously, as you've said, it's voluntary. I mean, the other models or sort of models that are being explored for GLOBE and GUARD, which is obviously the other pieces that are not yet in motion, be it, they were under consultation as I understand it. And we did check before coming online to see if anything else had come into the public domain. We're waiting to see how that's all going to evolve, but GLOBE and GUARD are kind of similar types of assessment models looking at Medicare Part B and Part D. And there's some criteria around therapy areas, and certain revenue thresholds that apply. But the key thing there is that, it's proposed to be a mandatory model. So, there's no choice about whether to participate. And again, we're looking at that kind of true net price. It's a broader basket of markets that are being considered. I mean, we didn't flag specifically, but I'm sure everyone is aware that for GENEROUS, it's kind of key EU markets, Japan, Denmark, Switzerland, Canada, and then obviously, for GLOBE and GUARD, it's a broader basket, which includes a much wider range of European markets and some additional Asian markets and Australia. I think the key as well is that for GLOBE and GUARD, it's looking at the lowest price, albeit with some uplift. I think if you choose to engage and provide the ex-factory net levels yourself, there's a kind of an uplift. And if not, the idea is that CMS would estimate that for you. I think the key here is in both model, or three models, there's the idea that there should be some adjustment with PPP adjustment. So, trying to allow for different GDPs and that kind of thing. And actually, we've been doing that assessment, and it's interesting what comes out as the second lowest price for GENEROUS, or the lowest when you actually make those adjustments. But it isn't a simple or straightforward task to actually assess those prices. You would think it would be, but actually in reality when we're working with companies, it's not. So, I think that's an interesting learning on my side, but we'll see whether that actually comes into being.- Perfect, thank you, Cathy, very insightful. Clare. Last but certainly not least, if you would just introduce yourself really quickly, and then on the back end of that, what are you thinking about, what are companies thinking about, about how this will impact global pharmaceutical pricing?- Sure. Thank you for the introduction, and thanks to everyone who's joined today. I'm Clare Foy, I'm a director here at Petauri, and I head at the Global Value Pricing and Access team. So, yeah, just to add to what my colleagues have said, we're thinking about what will happen to global prices as a result of MFN. Obviously, as we've heard, the intention is to lower federal drug prices within the US, but we think this is likely to have an impact on pharma pricing worldwide. It's like a domino effect, you can't just change one thing in isolation, it's going to have a series of knock on effect. So, we've tried to think about what those might be. Obviously, there's lots of considerations to bring into account here. So, with GENEROUS as we've said, there's a requirement for net price transparency. So, if manufacturers do take part in that, it could lead to downward pricing pressure, and that might ultimately lead to a degree of global price convergence where US prices are coming down. As Michael and Cathy said, maybe commercial prices too, not just the federal prices. And potentially, some loss of confidential discounting because net prices are being disclosed. However, there is a bit of uncertainty about how this is going to play out in the medium to long term, and the effect, it might be less than first thought as referring back to the domino effect. There's lots of other things that might happen that means it's not quite as straightforward as just saying, oh, well, prices are going to come down. So, one thing we wanted to think about here is the importance, the strategic importance of the US market to pharma companies. It's been cited that about 40% of global pharmaceutical revenue is generated in the US, so it's a very important market. And that means that companies are going to be thinking very carefully about how to change their strategies. For example, as Cathy said, GENEROUS is optional, so companies may decline to take part, they might decide not to share the confidential prices required for GLOBE and GUARD. There is an alternative route where those would be calculated without companies disclosing those. They might not even be able to share those prices, as Cathy alluded to, it's much more complex than you might think. They may not know the prices and there may even be some reasons why they cannot be shared due to confidentiality. So, we'll think about that a bit more, I'm sure later on in this webinar. So, to answer the question, Steve, that you posed, we do expect to see lower US net prices for some in market products, at least to start with. But in the longer term, we think companies will probably explore ways to raise ex-US prices, or at least utilise some mechanisms to protect the net price as much as possible. They may also, of course, delay launching outside the US, so MFN as it's currently been moted to be might not apply, or they might not launch at all outside the US. And those things would of course avoid any price referencing as part of MFN. So, lots of things to think about and we can explore all of this during the webinar, but those are some initial thoughts.- Yeah, and just to build on what you said there, Clare, I mean, I think there's been some reports recently that actually have analysed, there's been a number of, you know, a slowing perhaps of rollout of ex-US launches over this period where the announcement has been made, and everyone's been watching and waiting to try and understand what does it mean. Like you say, you want MFN pricing, how, why, where, and then as we see more information with the bilateral deals and then these models being rolled out, I think some companies who are caught in the cross hairs as it were, really are holding back and waiting to see how things fall. So, there's been a reduction I think in a number of typical, continuation of global launch in recent times. And hopefully, that will stop when people get a bit more clarity. But I think it is, as you say, Clare, a very great risk. I mean, people are going to do the maths, they're going to do the trade off analysis and work out what is the least worst option. And it could be that some smaller markets are going to be in a very challenging situation. Hopefully, industry can find a way to be creative to ensure that patients get access to the products that they need in ex-US markets. We don't want this seemingly sensible idea that there should be alignment on price, but it shouldn't prevent access to patients in need. So, I think that's our role in supporting companies to find solutions.- Yeah, as we talked about before, Cathy and Clare, great comments. When they roll these programmes out, there's just so many unintended consequences as there was with Medicare Part D back in the day. It actually created grandfathering for so many products that it made it quite challenging for new products to figure out how to get onto the part D formulary. And in some cases, it would take an additional 18 months to find good coverage. And Michael, maybe I'll bring it back to you, maybe a basic question. How is MFN allegedly calculated if we can't see all the price? And then secondly, what does the pricing look like within the Medicaid programme? Maybe just to give a global reference of where those prices sit today.- Sure, so let me start with the second part of that. So, we tend to see a average, once we put together both the federal and individual state rebates, and ultimate agreements, we're tend to see discounts, 75, 80% is very common on average to get to that level. And so, as we look at the MFN pricing, the biggest challenge is, again, which drugs are going to ultimately be offered by the manufacturer, and are they offering it in all the various countries? I mean, a lot of manufacturers that have run into a situation where they only may operate in a single one of the targeted reference countries. So, what's the second lowest MFN pricing if they're only in one country? How CMS is going to really get to that MFN pricing, it's still vague. It seems like it'd be a straightforward calculation, but it's just not. And I really have to circle back on what both Cathy and Clare have mentioned as well. And that is, we don't know that manufacturers are going to be able to provide some of the information. And so, I think when you put all that together, how MFN is ultimately going to be calculated is still a question mark, and again, we'll continue to watch. And I still really firmly believe that there is, again, you were talking, Steve, about some of the disincentives that sometimes are created by this or rather unintended consequences. And one of those is that I really still believe that there's a strong incentive for states to really come back if they find out what that MFN price is, and to separately pressure the manufacturers to even go lower below that. And so, where we end up is just a big question mark at this point.- Perfect, thank you. And maybe I'll ask Cathy and Clare the same question but in slightly different ways. So, how does this actually impact, Cathy, for you, products that are already launched, and then, Clare, how do you think about it from drugs that are about to launch?- Yeah, so I think products that are already launched, and I think both sort of topics, it depends on who you are. Are you a big manufacturer that's already agreed that you're going to participate in this kind of approach, or have you already made nominal reductions in prices in the market? I do think that there, it's unlikely that in the general run of things, people are going to be able to make adjustments ex-US to narrow that corridor significantly. You can't increase the prices in most ex-US prices in general, I gave an exception or two earlier. And I think, even if we think about the recent announcement, the agreement between the UK and the US, where some of that was already announced, but it's now been formally kind of wrapped up in a bow with this US agreement. So, we're seeing an increase in nice thresholds, but obviously, that's for new products moving forward. There's also a commitment to perhaps increase the percentage spend on healthcare. Again, that was probably already part of the agreed plan, and it will only subsequently affect future things. So, to me the in-market products are generally facing the situation that the administration was hoping for, that there would be some narrowing of the corridor achieved via reductions in the US, well, rather increases in US rebates, it's not going to affect the price per se. But I think it's interesting, I think Michael's alluded to the fact, it's meant to be all products that are eligible, but maybe there's some exceptions there. For those companies that are not participating in GENEROUS or have not got formal agreements in place, what happens to them, how will they be pursued, or is it just the general expectation from the administration that they should do something and they need to plan for it? I think the more interesting question is, what do companies do in the future? And I think there's two parts to it, and I guess Clare can talk to one of those and we can hand it off between us, but the people that are about to launch, and maybe the die is cast, and the investment is there, versus those that are planning for longer term future. So, Clare, I'll hand it to you to talk about one those.- I think that is probably one of the more challenging,'cause we don't know how that will impact for companies that have products about to launch, but as Cathy said, it's like moving the goalposts during the game. The companies have already decided what investments to make in trials, they've already made some revenue assumptions, and thought about positioning and things, and all of that work potentially needs to be revisited. So, we are working with companies to try to help them think about scenarios that might crop up and how to prepare for those and what to do. But I think that is quite a challenging area, particularly, for those that are about to launch with all this uncertainty, and as we've said, it's changing almost on a daily basis. So, it can be quite difficult to know exactly what will happen and what will be the right thing to do.- And I think, I mean, the companies that we are collaborating with, they very much said that it's a thinking country by country, literally considering, okay, UK, what can be done? Do we have to think differently? Do we have to do a subpopulation assessment? Can we push this? Is there the opportunity to engage more with innovative agreements? I mean, it sounds dreadful, but that maybe make it a little bit more opaque to fully understand the true net level. I think historically, payers have always, or rather in recent times, there's been less interest in engaging in very complex outcomes agreements or what have you, just the administration and making it work and the risk that the payer's going to lose out. I do feel that perhaps in this global context, it's bigger than a single company or a single product, and maybe the authorities in various countries are going to have to be a little bit more flexible and a little bit more open to that type of agreement. Because as we've sort of alluded, the alternative is the risk that if you are attending to be a lower price market, there may not be possible for a pharma company to launch. Again, those that are familiar with negotiation strategy in terms, it's almost like pharma companies, BATNA has improved a little bit. Your best alternative to a negotiated agreement has shifted a bit in your favour, albeit that it's a challenging situation, but you have more perhaps to bargain with. So, that's our hypothesis, right? And who will know, and there are some therapy areas where they're too large, it'd be just onerous to monitor and track those types of things. But I think that is a possible solution that's being considered. I think also broader agreements, perhaps are thinking holistically trying to help the payers thinking about a price for delivering a service rather than just the product itself, which again, makes it harder to unpick the net price, but actually is providing value for the payer and not just holding them over a barrel and pushing the price up. And I do think that policy, broader policy change is necessary as well to perhaps do what is being done in the UK. Like perhaps encourage greater openness to spend ex-US, but we'll see how that all turns out.- So, Cathy, do you believe that we will see a change again to come back to, I will just call it value-based contracts or innovative contracts that those will come back in favour? Or will it just really be about dead net?- I mean, it's so difficult. I think there was an element within this UK-US agreement that alluded to these types of agreements. I need to dig into and understand that more. I just think it's an option. I think the ultimately what companies should be doing, and this is more where they have longer runway to play with. If they're now thinking about an asset that's launching a year or two in the future, or they're looking at their portfolio and making decisions there, I think, this is where they have more ability to make the right decisions about do we truly invest, do we pursue the right kind of data that will enable us to support an appropriate global price in ex-US markets. Maybe it's greater investment in a smaller number of patients to get where they need to go. I think, if you are in a situation where you have your data and you've got to make a decision how to make it work in each country, I think it will be country by country what is possible. Some countries, the infrastructure is there to do those types of agreements. Some countries, it's just much, much more difficult, or it doesn't fly. Maybe there are alternative ways, or maybe there's some potential to collaborate. It's almost like we believe in the product but we don't have the data yet. Can we do some sort of, I don't know, conditional reimbursement, not in the traditional sense where it's just to gather the data, but you set a price that will work for the company, and then you gather the data that reinforces. I don't know, it's an option, or it's looking at a more restricted population, or, yeah, delaying and gathering that data separately, or using those markets where you can launch and gathering real-world evidence or be it, that's less valuable for payers sometimes. But it is tricky and companies are literally having to think about it market by market. And we've also been working with affiliate companies to think, well, how should we be working with the global team now? What do we need to do? Maybe our voice will be a little bit more resonant these days in terms of the requests we're making for particular data. Maybe that is, again, a positive outcome, but it's expensive investing in the right trials for some of the evidence-based countries.- Perfect, thank you. And Michael, I guess, in the US, the CMMI, piece of this, can you maybe define that a little bit for the group and do we anticipate seeing more and more participation there as well?- Sure, so the CMMI has always been an attempt to try to test different pricing models. And so, when it was first created, since that time, there's been over right about a hundred pricing models that have come out that they've tried. They usually are in five-year timeframes where they are trying to test those models and go into ultimately a evaluation period, monitoring evaluation and ultimately determination, is there cost savings associated with this model, and/or improved health outcomes. And so, out of that, what we've seen is about 25 models, or so that ultimately became mandatory, and actually have remained and applied. So, we're going to have to watch and see what will happen with these models going forward. Ultimately, again, that's a big component of it, is once we get whatever participation we're going to have from the manufacturers, then the question is going to be what participation do we have in the states? And ultimately, what is that monitoring evaluation going to show in terms of, what is the success? And that's one of the things, Steve, that I keep going back to is, how is the administration going to assess that it has been a success, is it the number of manufacturers that have joined and participated, the number of states that are using the drugs themselves? Or again, is it going to be at the core, the CMI model calculations of did it save money, and did it improve health outcomes? So, there's a wide range in trying to understand and really raise the question of what will happen with these models going forward, will they ultimately be converted into mandatory models? And again, we are so far at the beginning of this with just so much uncertainty and I just go back to what Cathy was saying, the policy environment is just changing so fast. By the time we get off this webinar, there may already be changes. So, we're going to have to see what happens between now and after the midterms. Now, I personally believe that lowering drug prices of the US is a bipartisan issue, I think it's supported by both sides. The question is what models or what techniques are used to make that accomplished? And so, a lot of question marks, and again, I do think the midterm elections are also going to be a time for reflection to see where is the new direction going to go after that timeframe. And that's just about the time when this first model GENEROUS in particular is going to be implemented around that same timeframe. So, a lot of questions still up in the air, Steve.- Perfect, thanks. And, Clare, kind of maybe digging a little bit more of what Cathy was mentioning before. What do companies or clients need to be thinking about in terms of the actual evidence generation, population size? What's the practical implication about the value of the drug or how to develop the value story?- I think there's a few things that companies can think about, and really different strategies and levers that can be used to help to optimise their situation. So, Cathy did allude to things like possibly limiting the target population, the label could consider generating evidence specifically for a defined population that might lead to potentially higher price potential, but lower budget impact. Something to consider maybe for rare disease, but also for other areas too where companies can think about, where there is an area of high need and defining a subpopulation that might benefit from new interventions, so that's a possibility. And then, hand in hand with that generating robust evidence to meet payer needs. So, obviously, there'll be a need to continue to invest in trials that meet requirements of key markets. There are some big European markets that have some quite stringent evidence requirements, so that's not going to change anytime soon. In fact, it might become even more challenging. So, I think some due consideration to what the right approaches to generating evidence will be very important. For example, head-to-head trials with active comparators where those are available, payers love that sort of trial. It's nearly always requested or desired, but, of course, it requires planning and investment, it's a bit more of a risk for companies, and obviously, a bigger investment. So, lots of thought about what might be possible, what the potential outcomes would be. We are recommending to our client scenario planning and just really thinking through all of the options that are available as well as what might change in the future. But what options are open to them, what might be the right courses of action to consider. So, yeah, those are some thoughts in response.- Perfect. So, you said differently, do you think the information that are going to be needed in the US to justify these prices will be there if they've been there for a while in Europe, right? The evidence that's there is rated and ranked, and the evidence kind of drives the value of the product. Do you think that we will start to see that narrowing of the gap that will be required in the US as well, because ultimately, you'll need it for all the markets?- Yeah, I think so. I think we're already seeing trends of that nature, and certainly outside the US, and I would say within the US as well. I mean, it's something that payers can easily ask for. They want to be convinced there's always pressure on pricing and that's increasing over time. So, it's definitely something that if I was a payer I'd be saying, I want to be convinced of the value of the products. And how can we do that? Well, I could put in some requirements about the evidence that I need and the trial design and stuff. So, I think that certainly is a trend that will continue.- Got it.- Yeah, and I guess in the US, and the evidence is to support up positioning and uptake, and it's not ultimately supporting your access to the market, well, I mean, within reason obviously the regulatory step, but it's not defining the price, whereas in Europe it is, and I think that's the difference. So, I think you're right, Steve, that perhaps that difference in evidence may be narrowing, because maybe in the US you are interested in generating that data to support your uptake later on post-launch, but it's essential to getting you up onto the right price level in ex-US markets to address this current focus on MFN global corridors.- Yeah, it strikes me that, I think you mentioned it earlier that maybe you delay launches in certain markets to generate the data that might be more difficult to do. So, you may have a launch that the label is still pretty thin at the beginning and there's questions. So, do you think that if a manufacturer will just say a rare orphan product in the US is able to get the product on market, and then start generating data, will that help increase its value in Europe, or should they still continue to consider launching them simultaneously as they more frequently do today, and that's for anybody.- Yeah. (chuckles) There's so many strands to it. I guess a very cynical view is, at the end of the day, you need to launch in the US and get revenue. I mean, particularly, if you're a company with only one or from product thing, I think, launching simultaneously, the Europe is not going to view the typical data that you might have. You can get approval for an orphan where product in the US with a less robust set of data and you could probably set a price that is validated. You're meeting an unmet need, these horrible conditions, patients need the product. You can get onto the market with that price, with that same single arm, early phase two, whatever data in Europe. Obviously, you can launch, but it's more challenging, and they are probably going to have less of a view of the value. So, I think, the difference here will now be that while you might well have just launched and seen a big difference, I think moving forward, you're probably going to launch in the US, get revenue, and then as you say, gather additional data, whether it's real world US data, or whether you continue with a more robust trial. I think, probably European payers are going to prefer the RCT approach, but real-world evidences is important, and maybe that's another area that will evolve, like ensuring that we can gather real-world evidence in the US that is more appropriate or applicable for ex-US evaluation would be an interesting topic.- Perfect. Clare, anything to add there?- So, if we're thinking about the pros and cons of delaying launch outside the US, I think we also need to consider other policies. It's not just all about MFN, there are provisional changes to conditional exclusivity in the EU. And these have been proposed so as to increase access to medicines across the EU and presumably to encourage engagement with the JCA process. And these changes will potentially shorten the time until generic and biosimilar competition, and obviously, impact on revenues by doing that. So, it's important to think about this when considering the timing of launches within and outside the US. So, if we think about the current situation, there's a baseline, well, sorry, the proposed, the baseline exclusivity will be eight years of data protection with one additional year of market protection unless manufacturers meet certain requirements and the requirements are numerous, but some of them include whether a product addresses an unmet medical need. So, that's where perhaps the rare and orphan conditions come into play. If the product brings a significant clinical benefit that confers some additional protection, and if the product contains a new active substance and meets certain conditions for clinical trials, so as we've been saying, for example here, conducting comparative clinical trials in several member states, so we're talking about the EU here, so they want multiple European trial centres. And most importantly, perhaps the manufacturer has to apply for more marketing authorization within 90 days of the first marketing authorization outside the EU. So, if you are talking about delaying launch outside the US, you've got to make a decision whether you want to launch in Europe, and the impact of the timing of that decision,'cause if you delay longer than 90 days, you lose out on 12 months of additional exclusivity. So, that could be quite significant. So, yeah, obviously, companies will need to weigh up the timing, the scale of the European launch. I think as we've said, the US is no longer a source of safety net when it comes to price. We will probably see at least some movement of pricing, although, as we've said with all the caveats that things are changing. But it's another thing that companies will need to wrestle with and think about. And as Cathy mentioned, it could impact patients,'cause if they're delaying or even choosing not to launch in certain markets, then, of course, that impacts patients. And then, there could be other pressures from policy and patient groups and so on. So, it's really important to think about all of these things. And then, on the flip side, if companies are going to launch in Europe, then they do need to think about JCA and the timing required there, it's been well talked about already, but there's a hundred day clock, which starts once there's an intention to launch. And companies have to get all this very heavy, robust evidence together in that time, including things like anticipating the PICOS, generating the evidence that's needed. And again, that puts pressure on timely decision making. So, there's a lot of things that have to be considered and as early as possible really, and that doesn't make things any easier, I don't think for companies.- I was going to say, as I listen to you speak, there are just so many variables here to consider. There probably isn't, I'll say, a right answer, if in fact your right answer is based off of revenue, there's probably a different answer if it's based off a patient, with a lot of these drugs, get access to these drugs to patients as quick as possible. And it's just interesting that there's just so many things to consider here. Cathy, I cut you off there.- No, no, I think I was just observing that in one way, this is a bit of a dampener on potential revenue. At the same time it's also, you could try to get around that by greater investment to provide the data and get ready for JCA and global launch. So, it's almost like, there's a sort of seesaw, and I think, it really very, very much depends on a company's individual situation, like how many products they've got, what kind of product, and making the right decisions about their pipeline, and investing in the right way. Because as you say, if it's purely based on revenue, then it might be quite a stark decision. And there may be some markets that are missing out here, or people taking the plunge. And actually, as you say, Clare, the engaging with the risk of generating the right data that would support the price that you think is appropriate. And that can be achieved in the US to balance out the global pricing. But I do think people have to make that assessment for their own company.'Cause we're working with organisations who are smaller, maybe they've set the price in the US or they're about to, and then, they may historically have been thinking, considering launch themselves or partnering. It's very challenging to evaluate what the value of the product is ex-US, and do you want to lose control of the strategy in those markets, because it obviously, has an influence on your US revenue too. It's very, very tricky.- Yeah. And Michael, just thinking about this from a Medicaid perspective. So many drugs that are coming out are paediatric, and they have such a bit profound impact on people's lives. SMA, muscular dystrophy, there's just a lot of agents in the pipeline, I think we've heard it called the $400 billion question. There's so many drugs in the pipeline that are getting ready to come out. How are states thinking about the affordability here? If prices potentially go up in the US, and the Medicaid budgets generally need to be on a balanced level, what does that look like? Is there a tipping point here where people just say, "Enough."- Steve, that's a great question, because we've already started seeing it just as we, again, starting with SMA and some of the others, and then, moving into most recently metachromatic leukodystrophy and some of the others that when we see those dollar amounts go up, yeah, that state budget pressure does become huge. But because of that paediatric indication, there's a huge caveat that states have to deal with. And that is the federal requirement under Medicaid of early periodic screening, diagnostic, and treatment, EPSDT. That provision of Medicaid law basically says that any state of a child presents with a medical condition whether or not that state actually covers that benefit in this case, maybe that high cost drug or that treatment, they have to do it, they have to find a way to make it happen. And there's only a very few reasons that a state is allowed to not cover it. And so, they ultimately are going to have to look at how do I build it into my budget? How do I sit there and address it, because I've got to cover it for these children. And if they ultimately, if they don't, they're going to wind up ultimately into the federal courts, they're going to have to come in and intervene. So, states are very aware of that requirement, and so they're going to build a budget around it. But at the same time, and I don't want to digress, but at the same time, states are also dealing with the effects of H.R.1, the One Big Beautiful Bill Act from 2025. And those provisions are starting to become implemented right now, which is putting even additional budget pressures on. So, the short answer is that ironically for the paediatric indication, they're probably still going to get covered. The question is, who else is not going to get covered, or what benefits are going to be reduced for other persons that are in those Medicaid programmes, and how are state going to ultimately figure that issue out? And we already see it now where we have drugs that are approved only for paediatric population, even if it's one that bridges into adulthood. So, it's a great question, Steve, but kids are going to ultimately get the coverage, states are going to have to struggle to figure out how to balance a budget.- Perfect, thank you. It's amazing. There's so many drugs and development that are really going to change people's lives, we see it, and now we're all going to have to figure out more and more how to pay for it. And at the same time, how we started the conversation is, the US I think is looking to reduce its overall exposure and cost, but it almost feels like the unintended consequences, maybe in the short term that it will not ease. So, I guess the bigger question is, I understand the construct or how we threw it out there, which is MFN is supposed to help reduce cost for Americans and people living in the United States, but in fact it may have the opposite impact. I mean, dare I be so cynical? So, I guess the question is knowing that, how do you think the administration is going to react when prices really don't fall? How do we navigate that or manage that?- Yeah, Steve, it really gets back to that question that I was asking earlier, how is the administration going to judge success? If I put a cynical hat on it, I will say that the administration will say that we have a large amount of manufacturers that came to the table. They have offered tremendous reductions in the prescription drug pricing, and it is going to improve access to care all the way around. And we just don't know what information is going to be used to show that that's exactly what's happening. I think that it's going to be the administration saying that they have achieved their goals. And then, I think that they'll probably push back by some, especially the states,'cause they're looking at whether or not they're actually saving money, and then ultimately, you're going to have CMMI, in five years, they're going to have to come up with the data to say, did the model work or not? But that's going to be after this administration has left. So, how does that all play out? In the meantime, I think the administration is going to probably claim success early on before we actually have the data to really support whether or not that's accurate statement.- Yeah. There's lots of public announcements about engagement, and more products launching onto TrumpRx, and this kind of thing like the visible agreement to participate is something. I think it'll be intriguing to see the extent to which new launching products for different types of companies, shall we say are pursued. For smaller companies that haven't made formal agreements, or haven't engaged, is there going to be some flexibility? Is there an acknowledgement that it could be, a very different situation for those smaller companies. I think that would be very interesting to follow.- So, kind of related to that, Clare and Cathy, is it possible just to have separate strategies, one for the US and one for the global market? Or are we at the point, because of everything that you've mentioned, all of these variables, do you need to have one giant cohesive strategy, even if that means that you may not launch in certain markets, is it possible to leave it separate, or is it now, companies really need to think this through at the highest level as early as possible?- That's a great question, I can start, and Cathy can chip in. Yeah, I think it is important to have collaboration and think about the strategy as a whole. I mean, it's still possible to have separate strategies of course for the US and outside, but I think, I suppose what's important is thinking about making the decisions early, having the right information in your hands to allow you to do that. Thinking about the pros and cons, and what effects each decision might have on revenues, but also on patients, and on launch optimization in every country. So, there probably isn't a right or wrong answer to that, but we have internally been discussing the importance of companies collaborating internally with affiliates and sharing their expectations and the data that they have, and making those decisions together so that people are happy. I mean, there's so many different light and shade to this, it's quite hard to give a fully detailed answer. If pushed I would probably say yes, it's important to think about the strategy as a whole and not as two separate things.- Yeah, I would agree. It's going to be more joined up, it has to be, even if it's to decide to kill something early, or only launch it in the US. Right from the get go and plan your investment in trials accordingly. Or if it's yes, we've worked out a way to make this product work globally, and we're going to invest in the right trial to support that globally. I think it very much has to be more joined up both in terms of, I know this sounds a little bit silly, obviously, there is this joined up thinking already, but in our experience, sometimes the US and global can be a bit more separate. And so, I think there'll be more aligned thinking there. Plus, as Clare alluded to, more early input and validation with the affiliates. Again, that's obviously occurring already, but I feel like there might be more weight behind what is requested or asked for. And people need to be realistic, sometimes, I think there's a,"Oh, yes, it might be challenging, but let's just carry on." But no, I think it really is going to be essential to make the right decisions early. Are we going to invest, well, are we not going to invest, and make an appropriate plan.- Sorry. I just wanted to say, maybe it's more difficult to change your mind or adapt the strategy. It's probably more important to make decisions early and stick with them, because it's probably less possible to change or adapt strategies later on without having significant effects.- Perfect, thank you. So, maybe final question for each of you is, where will we be in five years? So, things are happening fast and furious. It's a hard question, because things are changing hourly, weekly, and even from a media perspective, we're just on a different clock, but if you were to forecast where we're in five years, what do you need to be thinking about if you're a pharmaceutical manufacturers as it relates to these policies? So, maybe, Michael, I'll start with you.- I think in five years, I think that the focus will still is not going to be lost on ultimately what is the pricing that is in the US versus in other countries. I think that that is still going to be a question mark that's going to be out there, and are people in the US paying a disproportionate amount relative to those other countries? I still think that that will be a question that will still be out there. I don't think that we're going to solve for it. I think that it'll be interesting to see how much of a change we do see. I think that you will see some downward pressures, and that we will see some areas, and I'll say it that way, some therapeutic categories, where I think you'll see probably more change than other categories. I can't pick those out at this moment, but I do think that'll happen. The biggest question really is going to be the next step is, how much it is going to go back to what we were talking about earlier, evidence that's going to be used to say whether or not this drug is really as effective as it needs to be. I think that's going to be one of the biggest changes that come out of this is, I think, additional effort in the US to really raise that question of effectiveness. So that's where I'll put my hat at this moment at time.- Perfect, thank you. Cathy, what's your wager?- Oh, it's tricky, isn't it? But yeah, for sure, I don't think this is going away. The extent to which it has an impact, I think we will see some narrowing, but I think, the ultimate systems of evaluation in the ex-US markets are not going to formally change, but maybe there'll be some more, as I say above product, above company, just more country to country agreements, or alignment on what is appropriate. Because I think that will be necessary to prevent some of the natural consequences of a business having to make an unfortunate decision about access for patients. So, I do think it's going to be broader policy pieces like we are seeing with the UK and the US. That being said, I mean, I don't know to an extent how what's been agreed there will actually come into being. It's not like some of it can be implemented, you can't force a manufacturer to engage with something necessarily. And I do think, maybe we're going to see perhaps more, depends on the therapy area, but more products, an option which we didn't talk about earlier is maybe more private access. I mean, obviously, there are some therapy areas where that's not going to be appropriate, but maybe a solution for some companies in some areas is to have more products that are going effectively"non-reimbursed." You can set the price at the level that you think is appropriate. It still obviously counts towards the MFN type calculation, but you have control over that. But obviously, that doesn't work for all therapy areas, but it's hard.- Perfect, thank you.- The crystal ball is hard. (chuckles)- Yes. And what do you see in your crystal ball, Clare?- I think it'd be interesting to see how other countries will react to all these changes. What policies might be put into place to ensure continued access for patients to new innovations in other countries. I mean, the EU changes that are being proposed, have happened independently to some degree at least, but there might be others. I mean, I think we might see some consortia of countries looking at policies to try to encourage companies to still launch outside the US. I think there is a risk that some companies may think that that's a possible lever that they can pull at least. And if that does happen, then payers and healthcare systems and patients, of course, in those countries will want to do what they can to ensure that companies still see launching there as attractive. So, I think we may see some changes going back to the domino effect. I don't think this is the only thing that's going to happen in isolation. I think there will be other things that happen too. I agree there probably will be some downward movement in prices, but I don't think that's the only consequence of MFN.- Perfect, thank you. Well, I wanted to thank our panellists today for sharing the reviews. Really insightful, very complicated topic. Really interesting topic as well as we try to figure out how to match value to some of these lifesaving drugs that are out in the marketplace. So, thank you for your participation today. For those that joined, thank you for taking your time to talk with Petauri and Artia today about some of the expertise that we have on staff. We do have a host of questions that have come in that we are going to follow up with, specifically for each and everyone, and we really appreciate it. So, thank you very much and I wish you a great day.