Encircled by heavyweight life sciences powerhouses of the likes of Germany, France and Switzerland, plucky Belgium nonetheless continues to astonish and project considerable influence when it comes to its abilities to develop, manufacture and sell medicines.
Despite representing only a mid-size marketplace from an in-country commercial perspective, the comparatively small European Union member state nevertheless has “a thriving and competitive biopharma ecosystem that encompasses the entire value chain, spanning research and development to manufacturing. The industry environment is robust, fostering the presence of both multinational companies and biotechs, with a particular emphasis on biological and vaccine expertise,” observes Paul Stoffels, CEO of the renowned homegrown biotech, Galapagos.
Indeed, over the past couple of years, against the backdrop of an increasingly uncertain and volatile global operating environment, Belgium’s medicines output has “come on in leaps and bounds.”
In the post-COVID period, the country’s pharmaceutical exports have skyrocketed from an already high starting base, increasing more than 70 percent, to the point where the multilingual nation state now habitually trades in excess of EUR 230 million worth of biopharmaceuticals per day to export destinations stretching from the European continent’s major economies all the way to the megamarkets of China and North America.
Export Springboard
How can such feats be explained? Part of the reason clearly lies in the country’s strong industrial prowess combined with an ever more sophisticated and expansive logistics infrastructure. Courtesy of its strategic placement close to the heart of the European continent and a stellar supporting network of air and sea lanes, the centrepiece of which is undoubtedly Antwerp-Bruges seaport, Belgium “has burnished its credentials as a platform from which it has become pretty easy to import and export products,” notes Tom Hautekiet, the port’s chief commercial officer.
“This is of particular interest and appeal to the (more than 30) pharmaceutical players already possessing production sites in-country as Belgium can nowadays be leveraged as a launchpad for exporting intermediates or finished product and harnessed as a vital node in worldwide supply and distribution chains,” he opines.
Such dynamics are immediately apparent in the prevailing strategies of Big Pharma. “In Zaventem, we have established one of the largest Pfizer logistics centres to be found anywhere, handling two-thirds of our global distribution and mobilising air, land, and sea corridors to deliver medicines to more than 170 countries worldwide,” confirms An Van Gerven, the company’s general manager for BeLux.
What we’ve essentially witnessed has been a massive and rapid upscaling, on behalf of both major and minor players, to serve rampant global demand
Caroline Ven, pharma.be
Meanwhile, the iconic Japanese biopharma player, Takeda, has elected to turn its Belgian operations into a major node for the worldwide production and distribution of its plasma-derived therapies. “Over the last two years, we’ve invested over EUR 400 million in our Lessines site, expanding the existing site and adding new warehousing and production facilities so we can reliably supply over 80 countries,” reveals General Manager Michael Nesrallah, who forecasts yet more growth to come for the site in the years ahead.
Likewise, Sanofi has been placing big-ticket investments in its Geel manufacturing and supply site in Flanders. “This site is essentially tasked with the global production of our blockbuster biologics such as monoclonal antibodies and therapeutic proteins. Last year, executive management took the strategic decision to inject a further EUR 120 million worth of investment into the site for the incorporation of a new global production line for one of our most innovative haemophilia molecules,” proudly recounts the French company’s country lead and Benelux general manager for specialty care, Johan Heylen.
GSK, for its part, has been assiduously overhauling its vaccine distribution hub in Gembloux where next year it shall be partnering with Yusen Logistics to construct a state-of-the-art, fully GDP certified warehouse and logistics center kitted out with cold chain storage systems, autonomous mobile robots, and automated guided vehicles.
“This facility, which incorporates cutting-edge technologies and the very latest, exacting environmental standards, will not only serve to consolidate our incoming material storage, but shall also enable us to distribute millions of vaccines more quickly and more sustainably to people across more than 160 counties while simultaneously reducing our CO2 emissions,” enthuses Emmanuelle Boishardy, VP and general manager for GSK BeLux.
That’s not to overlook, however, the important contribution that smaller entities implanted within Belgium, such as those producing active pharmaceutical ingredients (APIs), have made to bolster and expand the country’s pharma exports envelope. Even prior to Covid-19, Belgium accounted for a deeply impressive 13 percent of the EU’s total aggregated pharmaceutical exports, and now that share is likely to be significantly higher with the locally-embedded industry capitalising upon pent-up post-pandemic demand for non-Covid related medical treatments.
“What we’ve essentially witnessed has been a massive and rapid upscaling, on behalf of both major and minor players, to serve rampant global demand. This has been achieved by leveraging latent capacity within our nation’s manufacturing facilities as well as the profound capabilities of world-class logistics partners such as Brussels Airport, Liege Airport, and the Port of Antwerp,” elaborates Caroline Ven, CEO of Pharma.be, the association for originator drug developers.
“Many of these are now fully cold chain certified and appropriately equipped to deal with the highly specific conditions at which many of the new products coming onstream have to be transported,” she insists.
R&D Mega Hub
Belgium’s unique life science offering is even more intriguing and multifaceted, however. Despite only ranking as Europe’s 34th biggest country by landmass and 13th by population, Belgium consistently manages to find the wherewithal to invest over EUR five billion in pharmaceutical R&D every year, rendering the nation the fourth largest pharma R&D spender within the entire Union, and the first per capita by some significant margin. “This ability to outspend even far larger neighbours such as France is emblematic of Belgium’s coming of age as a bona fide, world-class pharma hub in its own right,” believes Heylen.
Such R&D largesse has been fundamentally rendered possible by the presence of a fully-fledged landscape comprising all the core ingredients of life-science value creation encompassing top-notch hospitals, institutes, medical universities, small and large enterprises, venture capital and a highly-skilled, diverse practitioner and clinical community ready to collaborate.
This ability to outspend even far larger neighbours such as France is emblematic of Belgium’s coming of age as a bona fide, world-class pharma hub in its own right
Johan Heylen, Sanofi
“Belgium has managed to place itself on the map and assert itself as an extremely relevant and meaningful location for Novartis because of the establishment of the so-called pharma-valley: a well-rounded enabling ecosystem straddling the full product life cycle from development and research, through manufacturing and conditioning all the way to supply chain and distribution,” perceives Novartis’ Country President Federico Mambretti. “And the confluence of these attributes – skills, expertise, versatility, support structures and incentives – mean companies like ours can comfortably invest, thrive and attain peak performance.”
“Historically the Belgian pharma scene has, of course, always boasted an illustrious constellation of home-grown icons like Solvay, Janssen and UCB, but this rich heritage has also been complemented by concerted efforts to fill in the gaps and entice in companies and investment across the full pharma spectrum,” observes Pierre Boyer, general manager for BeLux at Servier. Moreover, over time, this has set in motion a “virtuous circle that is self-perpetuating.”
Blending Breadth with Depth
In other words, rather than focusing merely on the commercialisation segment of the value chain as one might expect from any ordinary small or middling market, Belgium’s planners have been sagacious enough to nurture and cultivate a distinctly holistic setting that covers all the main bases. The resulting outcome is a simultaneously well-differentiated and compelling offering that makes it that little bit easier to decide to invest further.
At the same time, there are definite cultural characteristics at play that have helped smooth Belgian pharma’s ascension. “One nuance I notice in Belgium that stands in stark contrast to other innovation-rich markets such as the United States is the tightness of the community: from academics and entrepreneurs to industry, clinicians and policymakers. There is great deal of connectivity and interaction, and you get a sense that real trust has been forged over time,” discerns Takeda’s Nesrallah.
“Belgium’s biopharma ecosystem is further strengthened by close collaborations among academic institutions, hospitals, spin-offs, start-ups, SMEs, large corporations, and a well-developed logistics network. This collaborative spirit fuels innovation and facilitates the seamless exchange of knowledge and resources, contributing to the overall success of the ecosystem,” agrees Galapagos’ Paul Stoffels. “This ecosystem thrives on extensive knowledge in pharmaceutical sciences and a pool of experienced professionals. Notably, the biotech sector, especially in the realm of cell therapies, has witnessed significant growth, even comparable to renowned hubs like Boston,” he believes.
Wouter Piepers, the CEO of the regional association flanders.bio very much concurs. “Not only is Flanders rapidly turning into a hotbed of biotech where the translation of good science can be converted into high-profile spinoffs, but Wallonia is becoming a pioneer in niche bioprocessing and biomanufacturing for some highly specialised therapeutics…Just consider GSK’s development of vaccines, Takeda’s plasma therapies, Univercells’ activities in the bioreactor space or Becarv’s aseptic design and process engineering,” he argues.
Belgium’s biopharma ecosystem is further strengthened by close collaborations among academic institutions, hospitals, spin-offs, start-ups, SMEs, large corporations, and a well-developed logistics network
Paul Stoffels, Galapagos
Belgium’s dominance in the vaccines space is already well accepted with companies such as GSK tending to consolidate much of their capabilities in this discipline firmly in the country. “Belgium hosts three of our major vaccine sites – in Wavre, Rixensart and Gembloux respectively – including our company’s global headquarters for its vaccines division. All GSK’s vaccines that have the ‘-rix’ suffix refer to their connection to the Rixensart site where the majority of our vaccines R&D is conducted,” explains Emmanuelle Boishardy.
Some insiders also believe that this space is likely to see a lot more action thanks to the massive attention given over to vaccine development during the global pandemic. “Perceptions about viability have evolved rapidly, and the experience and awareness related to the development of the COVID-19 vaccine has resulted in a palpable boost for cancer vaccines. Big Pharma’s appetite and interest in cancer vaccines has certainly been re-stimulated,” thinks Eric Halioua, president and CEO of PDC*line Pharma, a Liege-based outfit deploying a plasmacytoid dendritic cell-line pre-loaded with peptides from target tumor antigens for their core cancer vaccine platform.
Meanwhile, the recent decision of Janssen to situate its first-ever chimeric antigen receptor T cell (CAR-T) development campus in Ghent’s Tech Lane Science Park is seen as confirmation of Belgium’s burgeoning preeminence in the field of next generation cell therapies. “We can be immensely proud that our country has been chosen to host to the first cell therapy production site in Europe. It proves that we possess the requisite talent and know how to makes top investments like this possible,” declared Belgian Prime Minister Alexander De Croo at the time.
“The most important raw material in Flanders is actually our brains and our staunch commitment to technological innovation, which is why biotech like this has become one of our showpieces,” explains Minister-President of the Flemish Government Jan Jambon.
Janssen’s own general manager, Maria Fernando Prado absolutely agrees. “I consider that the selection of Belgium [for our new CAR-T production site] represents a watershed moment and is positive testimony of the value of the country in terms of innovation capacity and intrinsic quality of people,” she posits. “It is emblematic of the genuine appetite and enthusiasm for development of new technologies here, beyond any additional benefits that might be accrued from its convenient central geographic location.”
Resilient Biotech
With over 140 operating biotech companies representing almost a quarter of Europe’s biotech market buttressed by a fully fleshed network of seven academic hospitals, 12 universities and countless research institutes, Belgium boasts a robust biotech landscape seemingly able to withstand even today’s febrile economic environment and successive downturns in VC financing.
“Against the backdrop of an economic system under pressure and a myriad of geo-political challenges, we are perceiving a tendency towards precision financing, whereby biotech investors are becoming more discriminate, disciplined, and demanding and there is a need for strong data and efficiency. Money remains available, but only for the right projects,” reasons Piepers of flanders.bio.
“What we’re noticing is that projects are being de-risked earlier – with a weeding out the good from the bad, and even the good from great – and the cost of money is higher. Moreover, the same shift is simultaneously occurring on the investor side, with highly specialised funds now driving decisions, while the IPO window remains closed for the foreseeable future,” he concedes.
When Ablynx was acquired by Sanofi, it had developed a stellar program in rare diseases and in the slipstream of that success, and building on similar yet different technology, Argenx turned into one of the most successful biotech companies on the planet. Galapagos is another fine example, now blazing new trails in CAR-T therapies, while Oxurion has been successful in bringing a first-in-class retina therapy from bench to market
Wouter Piepers, flanders.bio
And yet, for all of that, he remains optimistic about the staying power and resilience of the country’s biotech scene, pointing to the continuous churn out of exciting prospects and impressive track record of spin-offs that have actually made it into the big league.
“When Ablynx was acquired by Sanofi, it had developed a stellar program in rare diseases and in the slipstream of that success, and building on similar yet different technology, Argenx turned into one of the most successful biotech companies on the planet. Galapagos is another fine example, now blazing new trails in CAR-T therapies, while Oxurion has been successful in bringing a first-in-class retina therapy from bench to market,” he recalls.
Belgian innovation is also playing a role within Japanese giant Astellas’ global portfolio, as the company’s general manager for Benelux, Mark Dekker, explains. “Benelux’s global significance to the company and its potential for future innovation investments can best be illustrated by Astellas’ upcoming women’s health product,” he outlines. “The product was developed at the University of Brussels before being spun off into a local company called Ogeda and acquired by Astellas in 2017. Having already obtained FDA approval, the product will soon be launched in the US. It promises to be a game-changer in women’s health and is all based on Belgian research.”
Even now, there remains a strong pipeline of up-and-coming actors that have already raised funding to bring their promising candidates forward despite the prevailing “tough love” investment climate. Liège-based Imcyse, which develops a new class of active and specific immunotherapies for the treatment of severe autoimmune disease, for instance, recently secured an equity stake from Pfizer, while Leuven-based Flamingo Theraputics, which specialises in RNA therapeutics, announced a merger with France’s Dynacure. Ghent-based Confo Therapeutics, a spin out from Vrije Universiteit Brussels, for its part, recently raised a total of EUR 47.7 million in funding over nine rounds for its peripheral neuropathic pain candidate, proving that pathways remain very much open for the finest ventures.
Mastery in Clinical Trials
Yet another expression of Belgium’s innovation propensity can be seen in its longstanding reputation as a clinical trials destination country of choice. From a volume perspective, the country has traditionally outperformed its peers when it comes to guiding new therapies through the clinical trial process swiftly and efficiently.
For a start, the sheer number of clinical trial applications approved in-country each year has been growing steadily, rising from under 500 in 2015 to 574 in 2021, which has ensured that Belgium has ranked within Europe’s top three countries for more than a decade in terms of the number of clinical trials set up per inhabitant. Commercial trials have also tended to exhibit a larger footprint in Belgium compared to other European states. In 2021, 80 percent of the clinical trials applications approved were initiated by biopharmaceutical companies as opposed to emerging from universities or academic institutes.
Some of the key factors underpinning these achievements have been the superior quality of the country’s infrastructure — including its research centres and over 70 hospitals— and the level of expertise of researchers and authorities, including the Federal Agency for Medicines and Health Products (FAMHP). “Belgium is blessed with a high level of expertise for conducting trials so we can proceed with confidence that the trials will be carried out properly and that patient enrolment will work well. Additionally, there are therapeutic experts in Belgium who are well-known at a European level and worldwide, which means they can speak about their experiences with our medicines,” points out Servier’s Pierre Boyer.
I believe this market to be exceptionally attractive for early-stage trials due to the particularly speedy approval process on the part of the authorities combined with the plentiful availability of clinics that are Phase I eligible
Gábor Sztaniszláv, Amgen
Meanwhile, there is ample capacity to provide choice and to not risk encountering delays. “Structurally, it’s a really good setup because there is an abundance of hospitals and clinics that are well organised and well equipped for undertaking large volumes of trials, which from a drug developer perspective means there are a lot of options and possibilities,” notes Aspen’s General Manager Vanja Hoeben.
Crucially, Belgium also offers a highly favourable regulatory environment, having introduced an important clinical trials law in 2018 to ensure the practical implementation of the EU Clinical Trials Regulation (CTR). Under that law, Belgium has continued to implement its ultra-fast approval procedures for clinical trials, particularly for Phase I trials — a procedure that takes barely 15 days!
“I believe this market to be exceptionally attractive for early-stage trials due to the particularly speedy approval process on the part of the authorities combined with the plentiful availability of clinics that are Phase I eligible. Of course, the quicker the process is, the more cost-efficient it becomes so the timeframes do matter,” remarks Amgen’s general manager for BeLux, Gábor Sztaniszláv.
A further competitive advantage also relates to the presence of expertise in specific therapeutic areas such as oncology and haematology. One of the reasons Bayer prefers to run certain trials in Belgium as opposed to its neighbouring home market of Germany is the superior knowledge vested within certain Belgian hospitals and clinics.
“We maintain a relatively high tempo of trials out here, especially those involving oncology, ophthalmology, or cardiovascular, because the physicians tend to be highly engaged and familiar with the therapeutic areas while the larger hospitals, in particular, are greatly experienced,” confirms Werner De Prins, country division head pharmaceuticals & senior representative Benelux.
Cancer research indeed leads in terms of the number of clinical studies carried out in Belgium by therapeutic area, with 175 launched in 2020, accounting for 19 percent of the clinical trials in Europe to test drugs against cancer. Then there is also significant emphasis on viral illnesses (ten percent), and nervous system disorders (eight percent).
Attesting to Belgium’s sustained competitiveness as a research focal point, big pharma continues to invest deeply in in-country trials. “Novartis most probably possesses the largest R&D footprint in the Belgian industry with over a hundred active clinical trials at any one moment,” declares Novartis’ Federico Mambretti.
Meanwhile, Switzerland’s other iconic drugmaker, Roche, invested a full EUR 27.7 million into in-country clinic studies in 2021. “Unlike with many of our other European affiliates, for Belgium we’ve even established our own clinical trial operations unit employing over 30 personnel and conduct the full panoply of trials from Phases I to IV,” reveals Marie-José Borst, the company’s general manager for BeLux.
Benelux also holds particular resonance for Vertex, the US-headquartered cystic fibrosis innovator, which is now branching out into new therapeutic areas. “Benelux is considered a biopharmaceutical hub with a strong history of delivering clinical trials,” explains Paul Newton, senior country manager for Benelux. “Our clinical team reports directly to Boston and runs trials locally, having completed 40 clinical trials in Benelux of which 20 are in Belgium alone. These trials cover not only cystic fibrosis but also other disease areas, where we have been working with CRISPR Therapeutics on gene editing technology that could potentially transform the lives of patients with debilitating illnesses. Belgium is therefore a crucial market for Vertex, and we closely follow any developments that happen in the Belgian environment.”
Pfizer too has come up with a bespoke formula for the Belgian market. “With two in-house Clinical Research Units (PCRUs), the company stands apart from many of its peers by keeping phase I research within the business. “We possess two Phase I clinical research centers globally, the first of which is in New Haven, Connecticut and the second of which is right here in Brussels. This demonstrates just how highly we value the Belgian clinical trials environment,” explains Isabelle Huyghe, Pfizer CRU medical scientific advisor. “And we’ve even established a secondary satellite unit in Hasselt where people who come from further away can get initial screening without the need to journey to the capital.”
Eli Lilly, for its part, has even made Belgium home to the company’s European Clinical Trial Services (ELECTS) division. “We feel it is important to maintain a strong position in Belgium, both in terms of regulatory compliance from a European level and in terms of access to patients for clinical trials. The ELECTS division coordinates all clinical trials and manages all clinical material across Europe, Africa, and Asia, due to Belgium’s long-forged excellence in managing clinical studies,” claims Country Manager Frederic Clais.
The Perils of Complacency
Notwithstanding all this investment and Belgium’s clear historical prominence as a clinical trials axis, some stakeholders are beginning to fret, however, that the country risks losing much of its competitive advantage.
The main impetus behind these fears are external factors. Firstly, the rising cost of Belgian labour and its elevating effect on trial fees, and, more urgently, the expected impact from the EU’s CTR that came into effect in January and includes the creation of an EU clinical trials portal and database.
“From a Belgian perspective, a centralised EU clinical trial database potentially levels the playing field in Europe and diminishes one of our main points of competitive differentiation,” says Roche’s Borst. “Belgium has a historical advantage in clinical trials, but the new European regulation will undoubtedly be something of an equaliser,” concedes Pedro Facon, deputy CEO of the National Institute for Health and Disability Insurance (NIHDI), the second largest social security institution in Belgium after pensions.
It is vitally important to recognise that the achievements of the past are no guarantees of future success
Federico Mambretti, Novartis
This new EU uniformity requires policymakers and industry alike to think afresh. “While Belgium may no longer be able to move faster than other EU countries, that doesn’t necessarily mean that it still can’t differentiate itself. This is a moment for reinvention and a wake-up call if our country seeks to maintain its privileged position at the clinical trials high table,” counsels Borst.
Others agree. “It is vitally important to recognise that the achievements of the past are no guarantees of future success. If we maintain business as usual and stand still, then that actually means being overtaken and falling backwards,” warns Mambretti.
Xavier de Cuyper, CEO of FAMHP, nonetheless claims that the government agency has been conscientiously preparing for the new legislation. “The CTR rollout certainly has had an impact, but our extensive pilot project seems to have paid off in the first year of implementation and companies are still investing in trials,” he assures.
De Cuyper cites Belgium’s competitive timelines for mono-national Phase I clinical studies and FAMHP’s involvement in the European project on Simultaneous National Scientific Advice (SNSA) as a potential way forward within the CTR. “The SNSA pilot has a specific focus on, but is not limited to, multinational scientific and technical/regulatory advice to facilitate and accelerate multinational clinical trials within Europe to the maximum extent possible,” he argues.
The local industry itself, has also been identifying additional ideas for potential improvements that could help preserve competitiveness. “We can see merit in bringing individual clinical trial sites together into clinical trial centres which, as research moves into more niche and rare indications, should broaden the catchment area and boost patient recruitment potential,” urges Michel Collard, CEO of PharmaScan BeLux, a non-profit organisation established jointly by pharma.be and off-patent association Medaxes to create a comprehensive database on hospital drugs by aggregating shipping units from distributors.
Market Access: Ready for a Reboot?
Within Belgium’s own pharma market – despite a predictably reliable, albeit unspectacular, compound annual growth rate of around four percent – there are, however, clear signs of discontent around a deterioration in patients’ level of access to innovative medicines.
“The European Medicines Agency (EMA) fast-track procedures and rolling reviews might have helped to improve access, but once you’ve secured EMA approval, there are still a great many hurdles at the national level to navigate before patients can properly get their hands on innovative therapies,” regrets Pfizer’s An Van Gerven.
Indeed, the EFPIA’s ‘WAIT’ Indicator demonstrates that Belgian patients are having to wait considerably longer than their counterparts in other high-income European countries to access the same approved medicines. “Right now, we are ranking an appalling 23rd place among member states with the Belgian population habitually facing average waiting times of over 500 days,” points out Marie-José Borst.
Moreover, the situation for certain specific therapeutic areas can be even worse. “We’ve noticed that, owing to the complexity of the system, oncology therapies are taking around 540 days over here compared to only 130 days in neighbouring Germany,” observes Servier’s Pierre Boyer, while Takeda is reporting having encountered delays of up to 638 days for their orphan drugs.
When it comes to reimbursement there are also formidable obstacles to overcome. The drug reimbursement process has become more and more elongated over time and implies a lengthy approval procedure that must go through both the Commission for the Reimbursement of Medicines (CRM) and the Ministry of Social Affairs so can take 180 days. Then, finally, when the decisions eventually get handed out, they are often very disappointing.
Belgium is experiencing a serious access equity issue and that our patients have fewer options available to them than their equivalents in neighbouring markets
Emmanuelle Boishardy, GSK
“In 2021, Belgium had 21 negative reimbursement decisions, meaning no reimbursement at all, yet 90 percent of those same products were reimbursed in Germany, and 81 percent in markets like the Netherlands, Austria, and Finland…This means that Belgium is experiencing a serious access equity issue and that our patients have fewer options available to them than their equivalents in neighbouring markets,” argues GSK’s Emmanuelle Boishardy.
Another problem is that, once reimbursed, the approved reimbursement criteria are often much narrower than the product label itself. “A high number of products do get reimbursed, but usually at very low price and with a restricted patient population,” notes Amgen’s Sztaniszláv.
He identifies the need for practical mechanisms to ensure earlier access to breakthrough therapies and laments that the prevailing system is too rigid to allow for temporary or partial reimbursement before the official reimbursement decision is made. “I believe that involving specialty professionals would allow a more accurate and objective evaluation of whether a product has a significant added value compared to the standard of care…. This would enable high-potential products to enter discussions on agreeing on a price, whereas, under the current system, products frequently never reach this stage, resulting in many promising products falling out of the system too early,” he reasons.
Ivan Perrichon, general manager for French ophthalmology specialist Théa Pharma in BeLux, worry that the authorities’ tough bargaining on pricing may come back to bite it if it leads to therapies which impact public health not being launched. “Approvals are no simpler in ophthalmology than in other areas,” he begins. “But we do aim to partner with local authorities to face upcoming challenges, like progressive myopia, which is a public health matter, not just for Théa. It is a societal issue that must be addressed today if we want to prevent the cost in the next 20 years because of the associated pathologies that will arise. This also raises the question of sanitary dependence that might impact the healthcare system even more.”
Nor is incremental innovation sufficiently recognised by the reimbursement system according to Van Gerven. “If we develop a new application for an off-patent product, the authorities do not recognise it as an innovation. However, a posology of one tablet per day to treat a chronic disease like hypertension instead of several tablets per day is an innovative solution that will genuinely improve the quality of life of the patient, their adherence to the treatment, and will bring positive health, and ultimately economic, outcomes. It is short-sighted to ignore this,” she contends.
Others, such as Isabelle De Walsche, managing director for Benelux at Gedeon Richter, want to see more clarity and certainty. “In a market like the Netherlands, you can have pre-meetings, which have no impact on the outcomes, but at least you can get a feel for the state of mind of the commission. Personally, I like that, because you can get an idea of the objectives of both sides and a sense of where you stand well in advance of a formal decision being made. I very much miss that in the Belgian system,” she admits.
Paul Newton of Vertex – which has achieved reimbursement for all four of its cystic fibrosis therapies in Belgium and which can treat approximately 85 percent of CF patients in the country – is rather more sanguine. “The Belgian authorities are open to engaging in dialogue with the pharmaceutical industry,” he opines. “I have seen signals that they are listening to our concerns, and I hope that this continues. I believe that if we listen to each other, we can work together to create a sustainable healthcare system that benefits patients, healthcare systems, and society as a whole.”
Mark Dekker of Astellas is broadly in agreement. “In terms of the reimbursement negotiations for our oncology portfolio, when NIHDI recognises the value or benefit of a product, they will find a way to get it to patients. This has been the case for our therapies in refractory acute myeloid leukaemia (AML) and metastatic bladder cancer, which achieved reimbursement in 2021 and 2023 respectively.”
Dekker does however caution that “there is room for improvement in terms of adequately valuing what innovations like these offer patients and the overall healthcare system. Not all innovative medicines make it to Belgium and the gap between approval and availability is 534 days, far behind Germany (133 days) and the Netherlands (294 days).”
What then are the potential consequences of a dysfunctional market access process like this where only 50 percent of EMA-approved innovative products are reimbursed, fewer than in Greece, and where the timeframe to market can be often slower than Albania? “If such a scenario endures long-term, this might ultimately dampen the enthusiasm for innovative pharma to invest in R&D and clinical trials,” warns Borst, “because the bridge from having a fantastic portfolio to ensuring patient access cannot be taken as a given in Belgium and our innovation is only worthwhile if patients can gain access to it.”
“Though Amgen tries to participate in as many trials as possible, Phase III trials, especially for chronic diseases, present a big ethical dilemma because we have patients who are treated with our Phase III trial, but then, after the marketing authorisation is granted, we often have to wait too long for reimbursement. In some cases, we are asked to provide the product for free post-approval, and this can be challenging to sustain,” explains Sztaniszláv. “Additionally, the unpredictability of whether the product will be reimbursed or not makes it difficult to decide if we should bring certain trials to Belgium at all. Some manufacturers have even halted clinical trials in Belgium because of this, which is a concerning tendency,” he notes.
A ‘Medicines Roadmap’
To their credit, the Belgian authorities freely acknowledge the existence of market access challenges and the need to enact sweeping reform to correct the perceived obsolescence of the prevailing approval and reimbursement procedures. “It’s important to recognise that the current procedure has been in place for over two decades and that, although there have been plenty of incremental modifications over the years, the procedure has actually become rather complex and unwieldy,” admits Diane Kleinermans, president of the Commission for the Reimbursement of Medicines at NIHDI.
“The fundamental issue is that the original design did not fully anticipate the challenges we face today or accommodate next generation technologies or ATMPs such the new types of cell and gene therapies now coming on-stream. As such it is no longer completely fit-for-purpose,” she explains.
Additionally, uncertainty about the financial impact or performance of many new products has led to an over-use of managed entry agreements whereby risk is shared between government and industry. As NIHDI’s Pedro Facon explains, “These agreements, primarily for innovative medicines in areas like cancer and immunology, already account for EUR 2.5 billion of the EUR six billion medicines budget. While managed entry agreements, in and of themselves, are a good tool for diminishing uncertainties and preparing fundamental discussions on the permanent reimbursement of medicines, having so many of these early-on agreements outside of the standard permanent reimbursement model has become a real challenge.”
Minister of Health, Frank Vandenbroucke, consequently last year tasked the NIHDI with conducting a 20-month consultation process with several stakeholders including industry, patient communities, insurers, and the Federal Public Service Economy, the findings of which were subsequently presented in the form of a ‘medicines roadmap,’ which is still pending approval by legislators.
The brute reality is that, right now, we often lack the data and insight to pinpoint value. Companies often complain about being paid too little for their products, but we can also see that reimbursement is being granted to products which finally do not have excellent real-world data despite promising early trials. So, we want to iron out these discrepancies
Pedro Facon, NIHDI
Under the proposed amendments, reimbursement procedures would be streamlined, and patients should gain access to innovative drugs sooner. For an innovative medicine, the adjudication period would be reduced to four months by allowing a drug’s manufacturer to submit a request for reimbursement as soon as it obtains approval from the EMA. Moreover, for drugs that had demonstrated particularly promising potential but were not yet approved, the procedure could be accelerated to just two months.
One of the more eye-catching proposals on the NIHDI’s roster of propositions has been to limit the duration of reimbursement contracts to three years, renewable only once for an additional period of three years, when there is no current limit for the duration of contracts. This is designed to safeguard the public purse and prevent instances of being locked in to disadvantageous agreements long-term.
“The brute reality is that, right now, we often lack the data and insight to pinpoint value. Companies often complain about being paid too little for their products, but we can also see that reimbursement is being granted to products which finally do not have excellent real-world data despite promising early trials. So, we want to iron out these discrepancies,” reasons Facon.
The monitoring of evidence on the real value of medicines is also set to be reinforced with an independent ‘Real World Evidence’ platform that will monitor the use and effectiveness of drugs under contract. “We want the decision to reimburse a medicine to be based more on scientific knowledge and accurate and up-to-date data. Companies themselves should also make more efforts to scientifically clarify the beneficial effect of their medicine,” declares Facon.
What’s more, alongside measures to improve access to medicines, the reforms also contemplate increased patient participation in the drug reimbursement approval process. “We want to actively involve patients in CRM. Today, insurance companies are the voice of patients. In the future, we will also want patient associations to have a seat at the table,” he envisions.
No Quick Fix
So far, the industry’s response to the proposals has been mixed with stakeholders from R&D-driven drugmakers and medtech applauding the suggestions for increased RWE and greater patient involvement, but many fretting that changes to contract terms might entail further cost-cutting. “We welcome this initiative and recognise the ambition, yet we believe the suggested reforms are insufficient to close the gap and could even put our system even further at risk if implemented as currently suggested,” warns Borst.
Smaller specialty players are particularly concerned. “From an SME perspective, we are fearing the prospect of stronger price cuts because this can be lethal for smaller, pure-play originators,” admits Gedeon Richter’s De Walsche. “If you have few products and have to face price cuts of say 30 percent, then that’s a killer. Usually, bigger companies can diversify their products and compensate for the price cut with the sale of another. However, at our scale, we don’t have that luxury,” she contends.
Others are sceptical of the federal government’s ability to honour its commitments or even to be around long enough to implement them in light of Belgium’s current messy politics comprising upcoming general elections next May and an incumbent governing coalition composed of no less than seven different parties that, last time around, took 494 days to form!
From an SME perspective, we are fearing the prospect of stronger price cuts because this can be lethal for smaller, pure-play originators
Isabelle de Walsche, Gedeon Richter
“Those in power have the right vision, but it is exceedingly difficult under the current political circumstances to move initiatives forward. Processes and protocols are structured in a way that requires considerable effort to change anything. My fear is that although there are a lot of plans for reform now, elections are coming up in under a year and that may change everything,” confides Alexander Alonso, Benelux general manager at medical device company Becton Dickinson (BD).
“Frankly the situation was better in the past when we were able to sign an industry pact – the so-called ‘Pact of the Future’ – which handed us the stability and the sure-fire certainty of being able to plan for a five-year period,” nostalgically muses Pierre Boyer.
Meanwhile, many believe that the real issue that need addressing lies outside the scope of the reform plans and concerns the paucity of public expenditure on medicines. “Pharmaceuticals actually comprise a relatively small part of the big picture in terms of overall Belgian health spending. The share of medicines within the NIDHI healthcare budget accounts for a mere 16 percent. Therefore, whilst a 52-point roadmap about negotiating medicine costs may trigger some benefit, it ultimately impacts less than one-fifth of the total budget,” reminds Sally Ann McNab, general manager and vice president for Benelux at BMS.
“Let’s be absolutely clear, pharmaceuticals are not the cuckoo’s egg in the healthcare budget,” agrees Caroline Ven. “Healthcare expenditure is rising, but this is predominantly going towards infrastructure and staffing. Medicine expenditure is not increasing at anywhere near the same rate, and innovative medicine relative expenditure is actually diminishing.”
That drop in Belgium’s overall healthcare budget and the decrease in the share of medicine budget can be attributed to various factors according to Lilly’s Frederic Clais. “The automatic increase in salaries due to inflation is one such element that impacts our budget share. However, this decrease indicates that there may be an inclination towards perceiving innovation as a cost element rather than something to invest in… Real reform will only be possible when we can turn around that mindset,” he declares.
Generics: What Role?
With the Belgian marketplace registering generics penetration of only 16 percent, the second lowest in Europe, many market watchers eye an opportunity for the off-patent industry to be mobilised in helping the country better rationalise its public healthcare spending both by ensuring smarter apportionment of funds and in securing better value for monies expended.
“Currently, the prescription market share for generic medications is dominated by originator brands, and the situation has been even worse for biosimilars. Traditionally physicians have not been incentivised to prescribe off-patent products due to the price decreases which originator products are subject to once the patent expires. With prices of the originator and the biosimilar more or less the same at that point, physicians are instead more inclined to stick with the products they have been using for the past ten or 20 years,” notes Bayer’s Werner de Prins.
Vanja Hoeben, head of Benelux for South Africa-headquartered Aspen sums up the challenges facing generics companies in the Belgian market today thusly. “Belgian healthcare is under huge pressure to balance the costs associated with new innovations, but continual price cuts for generics are threatening the system’s sustainability and eventually these products’ availability for patients,” he states. “We are advocating for a more sustainable model, which automatically influences prices. Currently, once a product becomes off-patent, its price immediately reduces. Then, when there is a budget overshoot, we as generic companies are forced to pay the bill back via clawback. Moreover, in the last two years, and especially last year, inflation has risen, so there is greater pressure than ever on profit margins.”
“While originator products are important, especially for niche markets and unmet medical needs, relying solely on innovation without considering the importance of baseline care is neither a sensible nor sustainable approach. It is essential to create awareness that the off-patent sector plays a crucial role in providing access to basic medicines, particularly as the population grows and ages,” points out Jasmien Coenen, general manager of Medaxes, the association for the off-patent industry.
Belgian healthcare is under huge pressure to balance the costs associated with new innovations, but continual price cuts for generics are threatening the system’s sustainability and eventually these products’ availability for patients
Vanja Hoeben, Aspen
She perceives that, in Belgium, there has been a focus on paying for everything within a closed budget envelope that has neglected the real role of off-patent drugs in supporting the cost of innovation. “We urge stakeholders to see the off-patent industry as more than just a cheaper alternative. We promote healthy competition, which benefits price dynamics and fosters various forms of innovation beyond new molecules. Incremental innovations in dosage and other areas within the off-patent and generic sectors can contribute to extensive cost-effective and high-quality medicines,” she argues.
This especially the case for the genericised version of biologics where there is bountiful scope for identifying enhancements. As Nicolas Van Gelder, country manager for Celltrion, expands, “Whereas a biosimilar is a medicine that is similar to the reference biotherapy, we are intent on creating biobetters which is a modification of a biotherapy that has already been approved, with the aim of improving its efficacy, safety or patient comfort.” He gives the example of Infliximab IV which was launched as a subcutaneous formulation and has led to an improved version of the molecule that has been welcomed by healthcare professionals for its improved clinical features and by patients for its convenience.
Van Gelder also believes that the time is ideal for Belgium to start making use of these opportunities. “The blockbuster biologics developed 25 years ago, and which have driven industry growth over this period have all gone off-patent in the last five to seven years, meaning that the time is now for a rethink of where healthcare budgets can best be used and how authorities, academics & industry can come together to ensure that innovative medicines are made available to patients,” he muses.
At the same time, generics firms look set to receive a bounce with the news that the EU is intent on abbreviating intellectual property (IP) protection timeframes on originator drugs. “The possible reduction in IP protection for innovative medicines from ten to eight years in Belgium would be positive for the generic and biosimilar medicine companies alike. It would enable them to have quicker market access without hurdles such as backup patent linkage. This could well be the boost our members need to start contributing fully to this marketplace,” thinks Coenen
Naturally not many R&D driven drugmakers are convinced. “Restricting IP may seem like a bright solution to reduce costs, but it is not the right approach. IP is crucial for investment, especially for chronic diseases, and any restrictions on it may put the EU at a disadvantage in attracting investments compared to the rest of the world. Dropping the patent period might drive companies out of Europe and into the arms of more welcoming markets such as US, Japan, and China to invest their R&D,” warns Lilly’s Frederic Clais.
“The premise is that reducing IP periods will bring more innovation, when in fact the opposite is true. Periods of exclusivity and the stimulation of clinical research by laboratories are closely linked. IP provides reassurance in relation to the risks and costs involved in pharmaceutical R&D. If we create uncertainty and a less stable framework for recovering investments and freeing up margins for reinvestment, we risk breaking the virtuous circle of innovation in Europe,” frets AbbVie’s general manager for Belux, Renaud Decroix.
Nonetheless, the outlook for Belgium’s off-patent segment is decidedly looking brighter. “We’ve been noticing tangible progress of late,” says Stefano Christoffersen, country manager for BeLux at the Indian generics player Accord Healthcare. “Looking back five years ago, the overall penetration of biosimilars was pretty slow, but recently we’ve witnessed a real shift in the mindsets of healthcare professionals in hospitals and our strategy is beginning to bear fruit. Currently we possess four possess four biosimilars that have achieved reimbursement in Belgium and of which we have launched two. Already one of those has reached a significant market share in hospitals so there’s much optimism,” he admits.
Rethinking Healthcare
What is becoming increasingly clear is that systemic root and branch rationalisation across the entire Belgian care continuum will be required if Belgians are to gain easy and equitable access to next generation medical science. “Whether we are talking about pharma, medtech or hospitals, we all have to rethink the way we fund and find innovation. We know that the innovation of tomorrow will become more personalised and specialised and to finance it all within the existing structures simply isn’t feasible. Both from a payer perspective, but also from a pharma industry perspective, we need to reconsider that model fundamentally in a way that is value-based, which brings us back to data, results and proper accountability,” thinks Karel Van De Sompel, director of GIBBIS, a pluralistic federation of the public and private social-profit healthcare sector within the Brussels area.
Stefan Gijssels, chairman of the Patient Expert Center, mirrors these sentiments. “By adopting a more integrated and process-driven approach, we can significantly improve the system, generate better health outcomes, and reduce costs,” he predicts. “This is an area with immense potential for improvement. Belgium already invests a significant portion of its GDP in healthcare, and the system is well-equipped with advanced medical technology and highly educated healthcare professionals. In general, there is adequate funding in the system, however, one challenge lies in the design of the healthcare system itself, which is heavily influenced by the suppliers of services, such as hospitals, doctors, and insurers,” he argues.
By adopting a more integrated and process-driven approach, we can significantly improve the system, generate better health outcomes, and reduce costs,
Stefan Gijssels, Patient Expert Center
For Marnix Denys, managing director of medical device association, beMedTech, the need to realign incentive structures and address power imbalances is especially pertinent. “Presently, the healthcare financing system in Belgium does not incentivise healthcare professionals or institutions based on outcomes or results. Instead, they are paid for activities and treatments and this traditional financing model creates a bias and may hinder the adoption of alternative patient pathways that could be more efficient and value-based,” she posits.
“Game-changing medical technologies often require a shift in the healthcare process, such as introducing home care or point-of-care testing. This poses a challenge within the current financing system, which primarily rewards activity rather than outcomes. The existing system may even create disincentives for healthcare professionals to embrace new methodologies and technologies. To overcome these hurdles, it is essential to involve health economists in the decision-making processes, alongside healthcare professionals,” advocates Denys.
Federico Mambretti concludes with a call for collaboration to ensure continued success for Belgium. “Externally, the future of Belgian healthcare and its global attractiveness is now on the table,” he proclaims. “Belgium is a country with a glorious life science history that has learnt how to punch far above its weight and thrive in the face of adversity. Now we must rekindle that original spirit and band together – industry, policy makers, practitioners, healthcare providers, payers and patients – in ensuring that this hard-earned competitiveness is maintained, and that tomorrow’s innovative therapies and medical advancements can be fully harnessed,” he declares.
