Pharma Market Access Insights - from Mtech Access

Rare Disease market access in the MENA and Nordic regions

• Mtech Access • Season 5 • Episode 16

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Where will you be launching your new orphan medicine? You may be confident that your Global market access strategy will support access in key launch markets like the UK, the EU4 and the US, but have you thought about other markets? Have you looked at the reimbursement requirements for rare disease products in the Nordic markets? Have you explored opportunities in growth markets, such as those in the Middle East and North Africa (MENA) region?

In this webinar,  our Global Market Access team compare and contrast access opportunities and challenges for rare disease treatments in the differing markets of the Nordic and MENA regions, asking: what does this mean for your overarching market access strategy?

Our Global Market Access experts explore contrasting regions to showcase the significant differences between international markets when it comes to:

 - Overall and rare disease patient populations
 - Access inequalities
 - Time to diagnosis
 - Access to innovation timelines
 - Healthcare funding
 - Health technology assessment frameworks

Robert Taaffe (Consultant – Global Market Access) presents his research into the market access conditions in the MENA regions, with a focus on the rare disease reimbursement landscape in growth markets in Egypt, Saudi Arabia, and the United Arab Emirates.

Michelle James (Associate Consultant – Global Market Access) showcases market access and reimbursement routes in the more established, yet smaller populations in the Nordic regions. Michelle will focus on access in Denmark, Sweden, and Norway.

Clare Foy (Director – Global Market Access) leads our discussion on the opportunities and challenges of launching in markets with different conditions and requirements, and how this should play into your overarching Global market access strategy.

Learn more at and request a copy of the webinar slides at: https://mtechaccess.co.uk/rare-disease-market-access-nordic-and-mena/

Discover how Mtech Access can support you with market access, pricing and reimbursement for rare disease treatments at: https://mtechaccess.co.uk/global-market-access-and-pricing/

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- [Narrator] 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.- Good afternoon and thank you for joining this Rare Disease day webinar where we'll be looking at orphan drug access in the MENA and Nordic regions. I'm Clare Foy and I head up our Global Market Access and Pricing team. For those of you that don't know Mtech Access very well, we are a global specialist health outcomes economics and market access consultancy. We have a track record and expert delivery providing specialist support to pharmaceutical and MedTech clients, and we work as a collaborative partner to healthcare systems worldwide. We collaborate with our clients to deliver credible exemplary work in an agile manner. Our global experts provide valuable insights to inform strategic decision making. Thank you to all for the questions you submitted in advance. We'll try to answer those throughout the presentation, but if you do have additional questions, please get in touch. There's also a copy of today's slides in the handout section if you'd like to have a look at those later. I'm joined by my colleagues, Michelle and Rob. Could you introduce yourselves?- Yeah, so I'll go first. My name's Michelle James. I'm an Associate Consultant of the Global Market Access team here at Mtech Access. I have experience in pricing and launch strategies predominantly in the EU for US and UK across a range of therapeutic areas, including rare diseases. And I'll be covering the Nordics today.- Great. And my name's Rob. I'm a Consultant in the Market Access team at Mtech. I work closely with Clare and Michelle, across a range of projects. As part of my role I have experience in a wide variety of markets, basically ensuring that clients have the optimal evidence generation activities in place to secure the success of their products.- Brilliant. So for today's discussion, you've decided to look at two very geographically distinct regions. Can I start off our discussion by asking what do each of these regions look like, including the healthcare infrastructure?- Sure. I'd be up to start us off, so I'll be presenting a little bit on the MENA region. So MENA is an acronym that stands for the Middle East and North Africa. And this region includes at least 19 countries and currently accounts for around 6% of the world's population. As we'll see, the MENA region is highly diverse. It's got different healthcare needs, priorities, and resources across these different countries. Although most of these are striving to provide universal health coverage. However, providing affordable healthcare is a common challenge as new therapies developed and the demands of resource allocation increase. So some countries such as those in the Gulf states, including UAE, Saudi Arabia, have made really significant investments in healthcare systems and infrastructure. So this results in advancement facilities, services and expertise. In fact, these countries now rank higher in the WHO's healthcare efficiency index than countries such as Canada, Denmark, or the USA. However, other countries in the MENA region have been unable to follow this trend. And I'd say there are many common challenges across this region, including a disproportionately high rate of rare disease, although we'll touch on that as we go through this discussion.- Great. And Michelle, the Nordics?- Yeah. So in comparison, the Nordics region comprises five sovereign states. So that is Denmark, Finland, Iceland, Norway, and Sweden. There are also three autonomous territories connected to these states. So Faroe Islands and Greenland are connected to Denmark and Aland, which is connected to Finland. But collectively, the region accounts for around 0.3% of the world's population. So in terms of the Nordic countries, they're quite well perceived as having, amongst the highest standards of healthcare across the world, all five sovereign states are featured in the top 20 for the best healthcare in the world, and these systems are almost exclusively publicly funded through taxation systems. As we're kind of talking about rare diseases today, the topic of rare diseases appears to have a strong presence in the Nordics, and a number of countries have in place or in process developing frameworks and policies to support the access and management of financing the treatments of rare disease. So for example, Denmark, Norway, Finland, all have national plans in place for rare disease. In Sweden, I believe in 2023, they highlighted that they were going to have a national strategy that was in development. And this conversation of rare disease is also further highlighted by the annual Nordic Rare Disease Summit. So it's happened for the past two years, now I believe. But essentially this summit brings together key stakeholders in the region each year and highlights the key challenges of rare diseases and how industry payers, patients, healthcare stakeholders can work together to overcome these. And of course, I'm sure some of these will touch upon today.- Great. So let's start. Could you tell me a bit more about the demographics within each of these regions and how they're expected to shift over the coming years? What impact this is likely to have? Michelle, should we start with the Nordics?- Yeah, so the Nordics is home to around 28 million people collectively, but the region is relatively sparsely populated, the exception being of course Denmark, which is one of the most densely populated countries in Europe. Despite this, the region has seen significant increase in population size. So it's grown, on average around 21% since 1990. And in addition, there are fewer and fewer children that are being born in the Nordic region whilst the proportion of elderly people is growing. So in 2022, the proportion of the population aged 65 years and older was 20%, and that's expected to rise to 28% by 2040. So you've obviously got the ageing population also contributing. This is the net positive migration and that accounts for two thirds of the population increase that's experienced in the Nordics. So Sweden, for example, has had one of the largest positive net migrations in the Nordic region. But kind of just to package this all really up, what we have here is this growing ageing population with fewer children born, net positive migration, which is essentially expected in future to have an impact and have increasing demands on coverage, expenditure for healthcare in the Nordics, including having additional funding needs for long-term care, increased use and access to health and social care resources, which as you know, is likely to have implications for other areas such as rare disease. So yeah, I guess Rob.- Some similarities, some differences, I think. So, I suppose in contrast to the Nordics, the MENA region spans three continents. So we've got a very highly populated but quite culturally diverse area. And as of 2022, I think the population was just shy of 500 million people. But this is expected to grow to around 700 million people by 2050 due to reduction in the death rates whilst maintaining a relatively high birth rate. Similarly to the Nordics though, the increase in the size of the ageing population is going to put enormous pressure on healthcare systems to provide suitable care for elderly patients. However, governments are reacting to these increasing pressures by adding new hospitals, new clinics, new health research centres, in addition to increasing adoption of efficiency improving measures such as digital health services and the establishment of functional HTA agencies.- Okay, thanks both. So now we've established some baseline information about the population and the healthcare infrastructure across both of our regions. Let's talk a bit more in depth about rare disease. So you've already touched on some challenges, but what does the rare disease population look like in the two regions? From my perspective, I think it's known that in MENA there are some quite high rates of rare disease. Is that right Rob?- Yeah, yeah, absolutely. So there's a relatively high proportion of consanguineous relationships across the MENA region, which has led to quite high rates of rare diseases. I think approximately 2.8 million people are known to have rare disease in the region, but this is almost certainly like a massive underestimate just to, due to the limitations in healthcare access, delays in diagnosis, and the lack of rare disease registries, which can really hinder the precise prevalence estimation of these patients. Yeah, rare diseases are associated with various challenges for healthcare systems and patients, including timely diagnosis and treatment. And these treatments tend to be quite expensive, quite complicated. They involve long stays in hospital and they represent a really a growing burden for governments and healthcare authorities in the region. Given as we'll come on too shortly, the limited healthcare provision for populations.- Okay, thanks Rob. And what about the Nordics, Michelle? Any similarities there?- Yeah, so by comparison to MENA, of the 28 million people that reside within the Nordics, there are about 1 million, I believe, to have a rare disease diagnosis. So that equates to just less than 4% of the region's population. So despite this comparatively smaller prevalence, and as I mentioned, good perceived quality healthcare, there does remain some challenges for the rare disease population in the Nordics relating to patient quality of care, quality of life and access. So in last year's annualised Rare Disease Summit within the Nordics, there were three key areas that were highlighted. So these were having limited awareness and knowledge around rare diseases, general advocacy by the public, and also challenges associated with assessing new and innovative treatments for rare diseases such as evidence generation to meet the standards required from each of the Nordic countries.- Okay, thanks. So you've both already mentioned some challenges around access. Could you tell me a bit more about these challenges across the two regions?- Yeah, I'm happy to start with that one. So as we mentioned previously, rare diseases collectively impose a significant burden on healthcare systems, especially in underserved regions across MENA, in which some systems struggle to provide access to care services, particularly the specialised and the advanced care treatments required for rare diseases. So there can be disparities in healthcare access and outcomes both between countries but also even within nations. And certain population groups experience poorer health and more limited access to services, for example, in Saudi Arabia, most specialised care for rare disease cases is provided in tertiary hospitals, located in large cities like Riyadh or Jeda. But many of those afflicted by rare diseases tend to originate in the more rural areas to the east of the country. So families in these areas may be unable to afford the transport across the country and do not really have either the finances or the education to know which doctor to see or which hospital to visit. So overall, there are increasing efforts to raise awareness of rare diseases in these underserved regions. And I suppose in terms of infrastructure, there's often lacking in many countries in the MENA region, brain drain is a real challenge with high rates of well-trained doctors leaving for increased pay elsewhere. And there are around, I think half the number of physicians per thousand people in the MENA region compared to the UK, although it should be noticed that these stats are not homogenous across the whole MENA region. And Gulf states, in particular, have higher numbers of physicians per thousand workers in part due to an increase in foreign borne health workers in many of the Gulf states.- Okay, lots of inequality there. So what about the Nordics, Michelle? How does that stack up?- Yeah, so for most part, access to healthcare across the Nordic regions is considered more equitable compared to the MENA region. Universal healthcare coverage is large provided for those that are eligible. In terms of the Nordics, they do spend on average more GDP on healthcare than the OECD average. And Rob you mentioned around doctors. So I think the Nordic regions have the highest, amongst the highest number of doctors per thousand in the population. So in Denmark that's something like 4.25 physicians per thousand inhabitants in Denmark, 5.18 I believe, in Norway per thousand inhabitants. But you know, despite this, you know, these things, inequalities do still remain. So there are, for example, still an unmet need in terms of waiting times and distance travelled to receive care. In particular for specialist care, as well as having the appropriate knowledgeable and experienced workforce to support the delivery of care across the countries. So this includes attracting and retaining healthcare professionals with relevant specialist knowledge and experience. And there are often, you know, especially in the rare diseases, particularly in sort of urbanised regions where you know specialists are few and limited in number. So some of these areas are, and unmet needs have been a key priority for many of the Nordic countries. So this includes making legislative changes to improve workforce shortages such as increasing acceptance of foreign doctors or having incentives for developing clinics as is in the case in Denmark, or increasing funding to ensure adequate training and supply of physicians in Norway. It's also important to note at this stage that in Nordic countries, the treatment of rare disease is often centralised within specialist centres or centres of excellence, which typically offer these kind of one-stop shops for integrated care and case management for individuals. So since patients with rare diseases often require sort of multiple different stakeholders within the healthcare system, these centres are considered of enormous importance in establishing clear care pathways for patients at all levels. So national, regional, and local healthcare. So this allows for more timely diagnosis and long-term better integrated care. Of course the trade off in structuring access is that for specialist diseases including rare disease, is there is the potential for inequalities such as burden of travelling to these centres or even exile due to illness.- Yep, certainly sounds challenging. So you mentioned earlier that some of the Nordic countries already have strategies in place to address rare disease. So do they have plans to reduce some of these access inequalities as well?- So I think the answer is a work in progress. There has been an increasing adoption within the Nordics of measures concerning regions and municipalities on slash local healthcare systems to reduce the impact of access inequalities through improving joined up or integrated healthcare between these centralised, highly specialised services and the care that can be safely and sufficiently delivered at the local level. So an example of this is Denmark, which has introduced municipal units in hospitals to support outreach and follow-up after hospital discharge to essentially avoid patients being lost in the system and also to ensure a high standard of care is delivered for those with complex healthcare needs. Such as of course, like individuals with a rare disease diagnoses.- Okay, thank you. Rob, you mentioned the aim of universal healthcare in the MENA region earlier. How does healthcare funding work across this region and what's the likely impact on patients with rare diseases?- Yeah, you're right. So we did mention earlier there's, well, there's a wide range of health systems in place across countries in the MENA region, most of which have quite fragmented healthcare systems and rely on funding from a combination of government expenditure, national health insurance schemes, and out-of-pocket spending. For example, in Saudi Arabia, 60% of the total health services are provided by Ministry of Health hospitals and primary health centres, whilst around 30% of healthcare services are private. However, all citizens have fully reimbursed coverage for orphan drugs from public providers. Although non-citizens are required to have private insurance through their employers. So I'd say over the past 20 years there's a general tendency towards spending an increased share of GDP on health, especially in the higher income MENA countries. As an example, the UAE forecast spend around 6% of the country's GDP on healthcare in 2026, which is up from around about 4%, I think it was 4.3% in 2018. So whilst this still falls short of the OECD average of 9.2%, there's definitely a clear trend upwards. And I suppose whilst most MENA countries would claim that they have comprehensive health insurance coverage in practice, incomplete coverage results in a substantial portion of pharmaceutical expenditure paid for out-of-pocket, the MENA region has some of the highest out-of-pocket expenditures in the world, which can be I think as high as 76% in Yemen and Sudan. It should be noted though that Gulf countries generally have low out-of-pocket spending on health services compared to other MENA countries. And I know the governments have been actively working to extend financial protections and enhance access to health services by utilising various risk pooling mechanisms. However, there's traditionally been a bit of a gap in both the knowledge and the policies related to orphan drugs and rare diseases in the MENA region, which has led to significant uncertainty for patients, for healthcare providers and for policymakers. Michelle, how does this compare, I know we've, we've got a little bit on the slide here. Do you want to talk a little bit to the Nordic regions?- Yeah, so as I mentioned very briefly earlier, by comparison to the MENA region, coverage is largely universal for those eligible and access is primarily owed to the primary financing of their healthcare systems through high public taxation. Although it's kind of important to note there is a growing yet really relatively smaller private healthcare insurance sector in the Nordic countries in which individuals are most likely to use this in the manner of covering out-of-pocket costs, co-payments, as well as other services such as gaining access to expanded range of private healthcare providers. So whilst there is increasing GDP spend on healthcare, the MENA region, the Nordics already, on average, spend a higher share of the GDP on healthcare versus the OECD average of 9.2%, I believe you mentioned. So Denmark for example, spends around 9.5% of GDP on healthcare and Sweden just last year spent 10.7% of its GDP on healthcare just in 2023. In terms of impact, kind of bringing it a little bit closer to home for individuals with rare disease diagnosis, the financial burden associated with healthcare access in the Nordics is also largely minimised, in particular, for those who might need to access or pay for services on a regular basis. And this is largely due to the minimal or capped out-of-pocket costs for which eligible patients are responsible. So as an example, in Denmark rare diseases, rare disease treatments are primarily delivered via the hospital route only. So meaning that individuals with rare diseases, there is no out-of-pocket costs for hospital care and inpatient prescription drugs. Of course, for any treatments prescribed in the outpatient setting, the costs are captive incrementally and there is a cost containment threshold set at around 4,000 Danish krona or around 550 US dollars annually. Similar case seen in Norway with additional centres in place to support those with permanent illness or long-term reduction in functional capacity. In terms of Sweden, co-payment rates are set by the regions, although the out-of-pocket costs do not necessarily vary greatly bet between the regions, but nonetheless there is minimal out-of-pocket costs for most healthcare benefits and schedules. So there's an annualised maximum out-of-pocket costs for all medical consultations of around 1,300 Swedish krona after which visits become free. And also a cap for drugs covered under the National Drugs Benefit Scheme, after which there's a subsidy. And just to kind of lastly note, Sweden also has sort of various forms of reduced-fee incentives, so across the region, so there are a few, but the most common is that patients under 40 with full activity and sickness compensation pay half the daily hospitalisation fee for the first 30 days of care as a sort of example.- Okay. Interesting. And what about funding specifically for rare diseases in the Nordics? Are there any healthcare funding incentives in rare disease?- So from what I'm aware, the short answer is no. So funding specifically for specialist and specialised prescribed products such as those in rare diseases aren't necessarily ring-fenced in the Nordics. And that's obviously, despite what I've mentioned, the voice of rare disease becoming stronger in the Nordics and also a number of countries having these national strategies in place to support the delivery of care for rare diseases. So in Denmark, treatments are funded by the hospitals and therefore the use of advanced treatments may be likely restricted to a single or a couple hospitals. Whilst in Sweden, funding decisions may be taken by individual regions often on the recommendation of the Council for New Therapeutics, depending of course on the reimbursement route. So outpatient versus inpatients. So treatments might not be administered if a region cannot subsequently fund it. So I guess that kind of lends itself to the identification, I guess, in the Nordics for, and not, well, not just the Nordics really, but a growing need for increasing funding to support access to innovative treatments in rare diseases as well as, you know, potentially more innovative payment solutions to support the affordability of ever more costly treatments.- Okay, and funding isn't the only challenge, is it? So we also know all too well that delays in diagnosis can result in mistreatment opportunities and that's certainly more burdensome in rare disease. What are the main challenges in reaching a rare disease diagnosis in each of your regions? Michelle, let's stick with the Nordics.- Yep. So the Nordic countries, as I mentioned, appear to benefit from having the delivery of care generally centralised into these highly specialised centres, centres of excellence that can tend to the complex need of individuals with rare diseases and can, you know, lead clear care pathways to manage these individuals. And that includes of course, timely and accurate diagnosis. So one of the challenges is that due to the rarity of orphan diseases, a lack of awareness and knowledge of signs and symptoms among physicians can still impact time to diagnosis. And that is true of the Nordic countries, which due to the comparatively smaller rare disease population versus other European countries and even MENA, most physicians, on average, will only see a small number of patients. So it does make it difficult to build up the necessary clinical knowledge and experience to recognise the symptoms of rare disease that is required for a diagnosis. And then in addition to this, you obviously have the centralisation of specialist care means that often, in the the local care setting, there are often few to no specialists for rare disease and there is a reliance on the GP or the primary care physician to be that main entrance level to care and refer as appropriate, provided they too, of course recognise the signs and symptoms or at least recognise something is not quite right. Just to kind of, sorry, second note around challenges to diagnosis is that it, I guess this is common to most countries as well globally and not just the Nordics, is that there is a limited public awareness around rare diseases which can hinder early detection and willingness to seek treatment. So in this respect, there appears to be an increasing push from some Nordics to include patient advocacy groups in not just raising awareness and increasing knowledge, but also on decision making in healthcare. And this is often because, you know, as you probably we all feel, patients with rare diseases often have more real-life knowledge and expertise about their diagnosis and treatment than the healthcare professionals and policy makers and representatives that they engage with. So Denmark, again, using as an example, there has been increasing collaboration with a national patient organisation, for example, as part of the national strategy for rare diseases. And that has been highlighted and this collaboration has involved, it has increasing involvement of patient representatives in policymaking. So in 2023 as well, this organisation was marked as a representative working group for decision making as part of their national rare disease strategy. Yeah, so I think that's everything I wish to add. Perhaps I'll just pass over to you Rob.- Yes, so similar situation, I suppose in the MENA region. I suppose on the awareness from rare diseases are frequently not either well known or understood by many healthcare providers, although as you just mentioned Michelle, like that can apply across most markets. That's true of most places. In some parts of the MENA region, the lack of specialised care centres and the limited access to genomic services are likely to contribute delays in diagnosis and that results in mistreatment opportunities. On the other hand, the prevalence of rare diseases has actually helped create a situation where doctors in the region's most developed countries such as Saudi Arabia that I mentioned earlier, have become rare disease experts. Although as I noted previously, this is often located in the larger cities. One additional thing to know as well is actually when diagnosing patients, many samples might be taken locally even from public hospitals, but they're sent to commercial and university research labs in Europe or even the US for genetic screening and sequencing, which can add further delays to diagnosis. I know that this is an area that some countries in the MENA region are looking to address.- Okay, and Rob, what about patient groups? Michelle gave that example in Denmark of how patient groups have an increasing role and their advocacy can therefore, you know, result in some changes to policies. Is there any sign of that happening in the MENA region?- Yeah, yeah, you're absolutely right. Patient groups can make a massive difference in terms of access and awareness and certainly where we are in the UK, patient groups in many cases can help push for the conditional approval of products prior to full regulatory approval. But whilst patient advocacy groups do exist in the MENA region, at least in Saudi Arabia, at least, none are currently dedicated to rare diseases. And that's generally the case in the wider MENA region as I understand it. And that provides quite a stark contrast relative to the US and Europe. So there are steps being taken in Gulf states to screen populations and create local databases which could be used in the quest to eradicate certain genetic diseases. And I'd say that whilst awareness is relatively low in parts of the country at the minute, part of the region at the minute active steps are being taken to improve awareness and to decrease this time to diagnosis.- Okay, great. So, so far we've talked about challenges around the population, funding, access to healthcare infrastructure and time to diagnosis in the two regions we're focusing on. I think it'd be interesting now to talk a bit more about access to medicines and specifically to innovative treatments in the rare disease space. What are the challenges you can tell me about in the two regions we're talking about today? Rob, should we start with you?- Yeah, yeah, absolutely. So firstly I'd say that the approval rate of orphan therapies in the MENA region is generally much lower than the USA or EU. For example, I think only one third of the drugs approved in the USA or EU are registered in Saudi. And the differences in the number of registered orphan therapies across the MENA region can be attributed to several factors, including variations in the definition of rare diseases, specific policies and incentives for orphan drug development in each country and differences in the regulatory approval process. So typically in the UK, we would generally expect highly specialised products to be assessed through relevant pathways and to be scrutinised by NICE. However, the use of HTA as a tool for the assessment and the pricing of products isn't really widespread throughout MENA. I think Tunisia is currently the only country in MENA with a independent national HTA body. And that was established way back in 2012 I think it was. In contrast, other countries in the region may have subnational payers or treatment institutions with their own private HTA units.- Okay, so is there something that's likely to change in the future?- Yeah, yeah, absolutely. I'd say there's a real desire from numerous countries in the region to move towards a more European style HTA system. It's just not quite clear at this stage what criteria those future bodies will end up using. There is a number of challenges obviously associated with setting up these bodies. So for example, the recruitment of specialised HTA professionals, the lack of public funding into HTA research and I suppose the limited legislation on the organisational structure. But as you say, you're quite right, like several countries have declared the establishment of national HTA body as the, as part of a major health policy priority. So both Egypt and Saudi Arabia as part of their 2030 vision have suggested this and we'll be keeping a close eye on it, I will be speaking with our various global associates on how these progress over the coming years. We may even do another webinar in a few years time on this very topic.- Great. I seem to remember hearing about that and I think it's been in discussion for a long period of time. We were actually asked by one of our attendees what the cost-effectiveness threshold might be in Saudi Arabia when they start their new HTA process? Is there any sort of insight you can give on that at the moment?- Yeah, so I suppose at this stage nothing, as far as we're aware, has been finalised, but obviously being able to identify decision making threshold is going to be key to successful implementation of HTA in any country. There was a paper released last year, 2023, which I think it received funding by the Saudi Ministry of Health, but it estimated that a cost-effectiveness threshold representing health opportunity costs would line the region of, I think it was 10 to 15,000 pounds per QALY although this would probably apply, I think it was to general pharmaceutical products. And we'd expect that to differ obviously for orphan therapies.- Yeah, it's often a higher threshold, aren't there, for such things. Okay, let's see how that develops over time. And as you say, perhaps we can do an update in a few years. So Michelle, what about the Nordics? What are the challenges for access to innovative treatments in rare diseases here, including the frameworks in place around decision making?- Yeah, so by contrast to the MENA region, the Nordic countries largely have established HTA and reimbursement decision making bodies. So Danish Medicines Council, the SBU and TLV in Sweden. However, one of the very few key challenges highlighted within the Nordic region is that despite their kind of established frameworks, access to innovative treatments can be somewhat hindered by the largely inflexible value/pharma economic assessments in place that evaluate new and innovative treatments. And balancing this with any decision making around what is more increasingly expensive treatments with ensuring access for rare disease patients to these treatments that is of course delivered in a financially stable way to the healthcare systems. So, you know, in terms of sustainable affordability, that's not just a problem specific to the Nordics, but also a problem globally. However, the funding infrastructure within the Nordic region can pose a few challenges, notably in the countries where there is a decentralisation of funding for healthcare. So for example, Norway funding for rare diseases has shifted to the hospitals whilst in Sweden funding can be regional depending on the route selected for assessment as I mentioned, outpatient versus inpatient. So this decentralisation can often result in a sort of fragmentation in the pathway between final pricing and reimbursement to decision making that occurs and the time to access for patients as the regions and localities work essentially to accommodate costs associated with reimbursement and of course implementing access to a new drug.- Okay, so staying on the topic of assessment frameworks, it'd be good to hear a little bit more about how drugs are assessed. Rob, could you start with the MENA region?- Sorry, just on mute. Absolutely. So infrastructure in the MENA region obviously varies, but as we mentioned earlier, the healthcare systems in the Gulf states have arguably leapfrogged western countries through rapid adoption of digital health technologies, regulation of AI medical devices, and various other routes as well. So if we had to start off with regulatory, there are two processes of drug regulatory review that's centralised and that's decentralised. So the centralised procedure involves the Gulf Cooperation Council, Drug Regulatory Agency. And this has several advantages for sponsors regarding direct submission, coordinated documentation, it's got approval for pharmaceutical products, medical devices. And additionally, I think the workload of registration is divided, which also improves the quality of the review and means that queries concerning the application are consolidated and are shared with the sponsor. And I think also previous pharmacovigilance and bioequivalent data can be shared between the GCC countries but obviously there's challenges as well. So a key challenge of the centralised procedure is that there's no real defined timelines for drug registration approval and that can extend anywhere from six months all the way through to 24 months or even more. And crucially, I think most orphan drug reviews take the same amount of time as conventional drugs. In contrast, decentralised procedures consist of the drug reviews, conducted by national regulatory bodies in the countries. But if a drug has already received registration with the FDA or EMA, decentralised processes within individual countries can be actually quite swift. So for example, the UAE implemented a fast track process for orphan drugs in 2018, I think it was. And thanks to that mechanism, the UAE is actually able to launch products really swiftly after approval is granted from either the FDA or EMA. So they might evaluate an innovative drug or an orphan drug application within 15 working days of submission and approve or reject within 10 working days from the data evaluation. And that kind of innovative mechanism is improving market access in that region. So the UAE is now considered amongst some of the first markets where a new product could be launched. And similarly, Jordan, Egypt, Saudi Arabia, all of these have a bridged regulatory pathways to improve access to medicines once they have EMA or FDA approval. Also in addition to like a bridged frameworks, countries like the UAE also provide research funding. They provide tax incentives and specific reimbursement policies to try and support the development and growth of orphan disease markets in that region.- Okay, I'd like to know more about pricing. What processes for pricing are used in MENA?- Sure, so in terms of pricing, I say external reference pricing is traditionally the most common used process and that generally results in low cost orphan drugs. But naturally a consequence of that is that they may experience availability issues or access delays for certain prescription pharmaceuticals or orphan drugs. And so these low prices combined with a maybe a high cost development or potentially a limited patient pool have traditionally discouraged pharmaceutical companies from launching orphan drugs in the MENA region. Although it should be noted that whilst the use of external reference pricing has traditionally been used, I'd say payer's willingness to pay in well-funded countries such as the UAE or Saudi Arabia is often substantially higher than any EU markets and actually is more in line with the US when it comes to orphan drugs. So those high reimbursed prices can make them more attractive markets to launch in and over the coming years, I'd actually anticipate that countries in the region will focus on the development of explicit value assessment systems and minimise their dependence on that external reference pricing over the longer term.- That's interesting and it is part of the reason we chose this topic isn't it?- Yeah.- Because, obviously companies have differing views on their launch strategies for these types of regions. So let's come back to assessment frameworks. Are there any recent innovations in the MENA region regarding assessment frameworks?- Yeah, yeah, yeah. So there's many innovations ongoing in that market. So I think of one or two maybe in Saudi Arabia just to sort of narrow it down. I think I mentioned previously how they've been increasingly using pharmacoeconomic evaluation methods to inform decisions around the pricing and the reimbursement decisions of new healthcare technologies for a few years now. And the establishment of a national HTA centre is intended to facilitate improved and equitable quality of care throughout the country. So the Saudi Food and Drug Administration actually recently released guidelines for orphan drug designation in June of last year and these were implemented in September. So those guidelines were intended to simplify the path for companies to develop and market their orphan drugs, expediting the availability of innovative treatments for patients who are most in need. And those guidelines provided, I think it was the priority review of applications for marketing authorisation. They provided the possibility of pre-submission consultations with the SFDA, so facilitating those early discussions about the orphan drug development plan and the regulatory requirements. And they also discussed the scientific and the regulatory guidance throughout the drug development journey. So the availability of those guidelines is expected to have a positive impact on meeting the specific healthcare needs of patients with rare conditions and is expected to lead to increase research and availability of orphan drugs in Saudi Arabia at least. And there are a number of other innovations ongoing in the MENA region and honestly I'd be really happy to take any conversations or questions offline if anyone does have a chance to talk through them.- Great, thanks. Yeah, just a reminder, if you have any questions for us or you want to get in touch after the webinar, please drop us a message in this chat. Yeah, so Michelle, over to you. How does that compare with the Nordic region?- Yeah, so I think Rob you mentioned a little bit about regulatory, so we'll start off there. So regulatory review of rare disease treatments when compared to the MENA region differs in that the Nordic regions can really rely and benefit from the centralised pan-EU procedure when marketing authorisation for a treatment is sought for the whole European economic area. So Denmark, Finland, Sweden are EU members, Iceland and Norway are not, but they are part of the European economic area agreement. So this centralised approach for marketing authorisation is compulsory under certain circumstances when seeking authorisation for medicines in the European area. So those are medicines such as those derived from biotechnology processes such as genetic engineering and advanced therapy medicine, orphan designated medicines are also covered under this. So the assessment under this route is undertaken by the EMA and authorisation of a new medicinal product takes typically up to, I guess 210, I'll say active days. So then the days kind of can be long best based on the stop start clock, but that can be reduced to 150 days if a product is granted accelerated assessment. Although it's important to note that drugs that are orphan designated do not always automatically apply, the accelerated assessment doesn't automatically apply to orphan designated drugs. And then at the reimbursement and pricing level, I think I mentioned that earlier, Nordic countries tend to adopt a value in Pharma economic based assessment methods when assessing new and innovative therapies. So this is the case for Sweden, Norway, and Finland which used cost-effectiveness evaluation methods. Denmark previously benefited from a clinical benefit evaluation, but since I think 2021 has moved to a cost per QALY system. So manufacturers obviously wishing to gain entry into the Nordic regions will be expected to submit their typical clinical and economic data for technical assessment.- Okay, that's interesting. So are there any particular challenges with this, especially in the area of rare disease?- So of course cost effectiveness and Pharma economic evaluation are not alien. They are obviously well established not just in the Nordics but in other countries like here in the UK where Mtech Access are based but, you know, Sweden are also adopting cost-effective, sorry, Spain are also now adopting cost-effective methodologies into their framework too, for example. But one aspect that poses a challenge for innovative treatments in rare diseases is that evaluation and assessments have varying degrees of scrutiny and flexibility between individual country assessments. So in particular, one challenge is that the population size and heterogeneity as well as limited historical clinical data in rare diseases can make traditional studies quite difficult or impossible to conduct, which often results in sparse data available for assessment or the need for increased flexibility around clinical trial outcomes and the use of surrogate outcomes for use as part of the Pharma economic analysis. Of course, when you kind of compare that to other countries, a number of Nordic countries appear to demonstrate some elements of flexibility within their framework. So for example, in Denmark, in the absence of data, companies can present available effect safety and cost data and also provide any sort of rationale as to why cost utility analysis might not be able to be conducted or included during submission. However, they do mention that to meet the basis of evidence requirements manufacturers could increasingly include sort of perspectives from clinical experts and also patient advocacy individuals, their perspectives when defining sort of the minimal clinically important differences for rare disease treatments to help with the value demonstration versus the current treatment landscape. In Sweden, there is also a lack of a clear published cost per QALY threshold. And, you know, therefore for rare diseases willingness to pay based on the Pharma economic analysis can differ on a case by case basis. And a higher ISA threshold can be applied, especially for treatments in therapeutic areas with a high or severe unmet need like rare diseases. So it's thought that this higher threshold is somewhere in the region of around 180,000 per QALY but it's imperative that,'cause it's on a case by case basis for manufacturers to ensure when engaging with payers that there is a clear demonstration of unmet needs and how their drugs will benefit the patient or the healthcare system, i.e. their value in their communication materials moving forward when they engage with payers. Just as a sort of really basic example of how to overcome some of these challenges.- Okay, that's interesting. So as cost-effectiveness markets, how does pricing work in the Nordics?- Yeah, so in terms of pricing, this tends to differ across the countries in the region. So for example, I believe external reference pricing is used in Norway and pricing is considered, I guess free in principle for countries such as Sweden and Denmark depending on the route to reimbursement. So when I say free in Denmark, typically outpatient medicine prices can be set by the manufacturer, but the final price is dependent on the cap set by the government. So, and then in terms of rare disease treatments, they are typically assessed and delivered via the inpatient route. So price negotiation in this scenario is delegated to Amgros, which, sorry excuse me, get my words out negotiates price and procures on behalf of the five Danish regions. For Sweden, prices for therapeutics assessed for outpatient use, for example, are submitted to the TLV by the manufacturer with supporting reasoning and rationale and obviously the adequate documentation to support the manufacturer's requested price. Whilst in the inpatient sector, the region's conduct a price negotiation. So often it's a sort of tripartite negotiation involving the manufacturer and also the Council for New Therapeutics, for example. I'm not sure if I mentioned this, but budgets are held by the regions in Sweden. So one interesting thing when it comes to pricing and an advanced therapeutic medicinal product in Sweden is that high cost drugs as a result can be unequally distributed across the region and can pose funding challenges. So there are exemptions that can be made between regions in which there are, you know, higher prevalence of some conditions in some areas. So costs can be shared between the regions and this could potentially be a model that could be applied for treatments in rare diseases moving forward.- Okay.- That is quite interesting about Sweden. So are there any changes or proposed changes expected in the Nordics around the assessment of interventions or in terms of accommodating higher drug pricing for rare diseases in the future?- Yeah, so I think one of the most recent examples that comes to mind is that of late October last year, the Swedish government agency, the TLV, proposed a new financing model for the introduction of rare disease medicines as part of its national strategy for rare disease. So in this report it was proposed that a higher price level should apply for orphan drugs covered by the Swedish national benefit system with the aim to essentially broaden access to medications for individuals with rare diseases. So as a sort of first step, an increased price level would be essentially traded for lower prices for more ordinary medications or medications that are more broadly sold within the sort of Swedish healthcare benefits system. So this is proposed to apply in the first instance for rare health conditions that are considered very severe and the prevalence is below 100 patients in Sweden. So where Sweden are in adopting these suggestions? Well, I guess that's what we're all waiting to see. But in terms of one thing that also came to mind was also in the rare disease sector in the Nordics has also benefited in the last decade or so from increasing cross-border collaboration with respect to HTA and procurement. So this includes the establishment of collaborative initiatives such as the Nordic Pharmaceutical Forum and FINOSE. So I think I can broadly elaborate on these if you are happy for me to continue doing so, Clare?- Please, please do.- Yeah, so in terms of, for those that are unaware, so the Nordic Pharmaceutical Forum was established by the Danish agency Amgros in 2015, so that this sort of initiative has the objective of solving access challenges associated with procurement and sustainability of delivering treatments within the Nordic region. So essentially making the Nordic region more attractive to manufacturers while strengthening the region's negotiation power and flexibility when it comes to procurement of not just, not just new and innovative products but also existing ones too. And also, so on the other side, so the HTA side, so FINOSE that was launched in 2018 by Fimea, NoMA and the Swedish TLV and it also now includes the Danish Medicines Council I think as of May last year. And that has the aim of increasing efficiency of HTA assessment in the Nordic region. So these will cover things like knowledge sharing, reduced divergence in the HTA methodologies and evidence requirements to essentially support a more time and equal access to innovative treatments and essentially reduce complexity in industry submission. So one of the key objectives of FINOSE was to overcome some of the challenges associated with the fragmented process and often duplicity seen in launching products across Europe and the Nordic region. So to attain this, they have set a 90-day timeframe to producing a public assessment report from the time of submission by the manufacturer to the joint process. So it's quite early in terms of its stages. I mean I suppose five years is really nothing, but there has been, you know, five products that have undergone this process. So we have things like TECENTRIQ which was for non-small cell lung cancer, XTANDI for prostate cancer. In terms of rare diseases, we had ZYNTEGLO which was for, a gene therapy for beta-thalassemia, Libmeldy for an inherited disorder in children with metachromatic leukodystrophy and VOXZOGO which was used to treat children for achondroplasia and open growth plates.- Okay, well it's great to see that patients are benefiting from this joint HTA route under the FINOSE collaborative. And how did they fare in hitting that 90-day time goal?- So I think a study assessing, I think, well, with the exception of VOXZOGO, so there was four products that showed that essentially where the study looked at those four products with the exception of VOXZOGO under the FINOSE joint assessment versus the sort of usual standard time to market access in each of the respective countries. So those assessed under the initiative were, in general, faster than the standard time in each of the individual countries. However, it did still take longer than the 90 days. So it does actually really remain to be seen whether the goal of 90 days will still be achievable in the long term.- Yeah, it'll be interesting to see how that evolves because we know that the EU are going to implement the standardisation of clinical assessment of interventions across Europe from next year via the joint clinical assessment. So as they are members of the EU and the EEA, how do you think the FINOSE collaboration will change with the advent of JCA? Do we know much about that yet?- Yeah, so I just kind of, one point I'm not sure I've added was that FINOSE or assessment under the FINOSE incentive at this stage is not necessarily about the final reimbursement decision, but it's obviously primarily centred around the sharing of data between the Nordic stakeholders to essentially produce a report based on relative efficacy and to produce a health economic analysis to expedite the final decision making by each of the respective countries. But back to your question around obviously the Joint Clinical Assessment, the JCA, so the JCA is primarily focused on standardising clinical assessment only. And I think we might have covered an article on the JCA if anyone wishes to look, but as part of that EUnetHTA, so that's the joint HTA, a pan-European body well has been contracted to support with the development of guidance to support this. So it wouldn't be surprising if FINOSE would build or explore the possibilities for FINOSE evaluations to then be built on the results of a Joint Clinical Assessment report. Especially as the FINOSE initiative has commitments to EUnetHTA and currently many of the EUnetHTA reports form the basis for FINOSE HTA, sorry, FINOSE HTA reports.- Okay, brilliant. Thanks for that Michelle. So there's clearly so much more we can delve into, but I'm aware that we're nearly at the end of our webinar today. So could I just ask each of you to give a quick summary of the markets you've been looking into? What are the take-home messages that our audience should be aware of? Rob, should we start with MENA?- Yeah, sure, sure. So if I had to summarise very, very quickly, I'd say that the MENA region is one with a quite a high disease population and burden, but healthcare spending in the region is generally increasing year on year. There's various innovations relating to rapid market entry and I think that combined with a general move away from external reference pricing over the coming years and towards more explicit value assessment systems makes it quite an interesting market to consider launching in certainly is one that I'm going to be keeping quite a close eye on. Yeah, Michelle, do you want to, do you want to give a quick elevator pitch?- Oh, the pressure. So, the voice of rare diseases, it is somewhat strong in the recent years within the Nordic regions and there are a number of key challenges that are being identified and addressed by the various Nordic stakeholders. So these include a number of initiatives to strengthen access to new and innovative medicines and to ensure the delivery of healthcare in a more sustainable manner. So we have things from potential shifts in the way medicines are assessed, like addressing higher cost-effectiveness thresholds, potentially required for advanced therapeutic medicines to more collaborative efforts to streamline the HTA process and reduce the time to reimbursement decision. So making, I believe at least the Nordics the more attractive market.- That's great. Thank you both. I think there's lot to look forward to, lots of innovation going on. So I think that was really interesting and hopefully everyone who joined us also found it enlightening. Thank you to everyone that has joined. We really appreciate your support. I'm sure this has also raised some questions, so you may be thinking now about how to tailor your global market access strategy with regions such as the MENA and the Nordics in mind. We'd be really delighted to help you. So please don't hesitate to get in touch with us if you want to discuss anything further. As I said, the slides are available. If there are any further questions, please get in touch and we hope to speak to you all again soon. Thank you.- [Narrator] 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.