France is considered among the leading rare disease markets worldwide, both scientifically and organisationally. The country has cultivated a fully-fledged supporting ecosystem for rare conditions that is today regarded as a benchmark internationally, and which few other countries have proven able to match.
“Back in the mid-2000s, under the then Presidency of Jacques Chirac, France was actually the very first country in Europe to implement a national plan dedicated solely to the management of rare and ultra-rare diseases,” recalls Aurélie-Anne Chausse, general manager for France and the Benelux at Japanese specialty biopharma, Kyowa Kirin. “And this model kick-started a longstanding tradition of political commitment and patient advocacy in this space, resulting in an enabling environment where diagnosis, referral and multidisciplinary care can nowadays be coordinated with real consistency,” she recounts.
That ‘Plan National Maladies Rares (PNMR)’ has, over time, matured into an intricately coordinated structure of 23 specialised networks – the so-called ‘filières de santé maladies rares’ – linking up national reference centres with regional competence centres, diagnostic laboratories, research teams, and patient associations. Consequently, those themed networks, such as FILNEMUS for neuromuscular disorders or CARDIOGEN for hereditary cardiac disease, can disseminate knowledge as well as provide organisational coherence and well-mapped out treatment pathways to the great benefit of patients, medical practitioners, and clinicians alike.
“What makes such a framework so highly effective is that it is around clusters of expertise and deploys a hub and spoke model with regional reference centres partnering directly with competence centres and local hospitals, while simultaneously tapping into European reference architecture enthuses Francois Rauch, general manager of argenx, a Belgian biotech best known for engineering antibodies for the treatment of complex autoimmune diseases. “This offers clarity to all stakeholders and provides clinicians with a fully integrated structure, meaning that patients suspected of having a rare disease can be swiftly routed to specialist teams without ever losing the link to their main treating physician.”
Need for Speed
Facilitating these multidisciplinary links is especially important in the rare disease sphere where speed is very much the name of the game. “For companies specialising in this field, success is neither measured in market share nor salesforce strength, but rather in how quickly patients can be identified, how swiftly treatment can begin, and how effectively therapy can be sustained over time,” explains Jean-Claude Roche, general manager of the French affiliate of Recordati Rare Disease.
“Having effective structures in place that facilitate the fluid exchange of expertise and the organisation of multidisciplinary discussions to coordinate patient care are a massive benefit and serve to empower rare disease therapy developers like us to work hand in hand with all stakeholders to accelerate diagnosis and ensure patients remain on treatment for as long as possible,” he continues.
Collective multidisciplinary action also helps overcome and alleviate one of the main impediments to effective management of rare diseases, which is the difficulty of initial diagnosis. “Rare diseases are notoriously difficult to recognise, and early symptoms often overlap with far more common conditions. Cutaneous T-cell Lymphoma illustrates this well, with skin lesions that can be misinterpreted for months before a biopsy and specialist referral secure a diagnosis,” observes Chausse. “Engaging closely with dermatologists and onco-dermatology teams vastly improves diagnostic accuracy, shortens referral times and helps clinicians identify the disease earlier in its course, which is why proximity to expert centres, patient associations and health authorities is so essential for positive end health outcomes, she reasons.
Chausse also gives the example of X-linked Hypophosphatemia. “Although it is a disorder of phosphate metabolism and skeletal mineralisation, it does not fall neatly within one speciality. For infants, it is the paediatricians, general practitioners, and orthopaedic surgeons who are most likely to encounter the bone manifestations first. Dentists can also play a critical role because recurrent abscesses can be an important indicator of underlying mineralisation defects. Whereas for adults, the front line of contact could additionally encompass rheumatologists and endocrinologists give the biology of the disorder,” she elaborates. “To ensure effective and speedy diagnosis, it is thus necessary to raise awareness across this diverse range of actors.”
Marina Vasiliou, president and managing director of the American neurology and rare disease specialty biopharma, Biogen echoes this sentiment. “Recognising the value of collective action and leveraging the excellent French ecosystem, we’ve been partnering with the Care Lab of the Institut du Cerveau (Brain Institute) to operate what we call a living-lab environment. This essentially strives to brings patients, caregivers, and clinical teams together to exchange knowledge, map obstacles in the care pathway, co-design practical improvements, streamline approaches, and better ensure continuity of treatment,” she recounts.
“Commercial excellence in this field relies on listening and adapting, because the variability of each patient journey means that conventional mass-market approaches simply do not apply,” she adds.
Genomics, Data, and Infrastructure
Another important aspect of France’s rare disease infrastructure has been its continued investment into genomics and national registries. “Genomics is becoming a critical part of rare disease care. Because a large majority of rare diseases are linked to identifiable genetic mutations, wider use of sequencing can help identify patients earlier, guide trial recruitment with greater precision and strengthen understanding of who is likely to benefit from a specific therapy,” affirms Celine Khalife, former vice president and general manager for France and BeLux at Alexion, AstraZeneca’s rare disease business. “Biomarkers offer an additional layer of insight, and together these tools can contribute to a more targeted and efficient pathway from diagnosis to treatment. she adds.
Since 2016, a major nationwide initiative has been in place, namely the Plan France Médecine Génomique 2025 (PFMG2025), designed to provide the nation’s rare disease and cancer patient community with access to personalised treatments using routine genome sequencing. Consequently, a national network of high-throughput genome sequencing clinical laboratories, including SeqOIA and Auragen, was established to process samples from across the country, leading to significantly improved diagnostic yields in the rare disease space. “The progress that France has been making on this front is really palpable, with the genomic plan reflecting a strategic understanding of both the humanitarian imperative and the economic opportunity inherent in genetic medicine,” believes Bana Jabri, Director of the Institut Imagine, Europe’s leading centre for research, treatment, and education on genetic diseases, located within the campus of the Necker-Enfants Malades AP-HP university hospital, a world-renowned paediatric facility.
Making the most of these assets is, however, predicated on the ability to embrace digital disruption. “One of the big bottlenecks presently lies in the incomplete management and integration of data. France’s next step needs to be to build a more connected, sustainable data ecosystem that allows these advances in genomics to translate into faster and more equitable access for patients. The country already possesses several national and hospital-based databases, but they remain fragmented and do not yet communicate seamlessly. This fragmentation limits how effectively existing data can support early diagnosis,” observes Khalife.
“Although issues of interoperability and data linkage persist, progress is evident and each year the system becomes more capable,” thinks Jean-Claude Roche, noting that the country has successfully established a Health Data Hub to manage the national health data system (SNDS), support the rare disease registry (BNDMR), and collaborate with the national research program on rare disease (RaDiCo) to consolidate cohort data.
Crucially, the latest iteration of the National Rare Disease Plan – PNMR4, 2023-2030 – has also introduced an important new priority: the application of artificial intelligence to sequence and analyse large volumes of samples with unprecedented speed. “With around 7,000 rare diseases, no healthcare professional can master them all, yet AI has the potential to transform diagnosis, whether through imaging technologies or integration into hospital systems. France has set itself the ambition to lead in this field, and this is a welcome and necessary step,” affirms Caroline Yau, general manager for France and Belux at Amicus Therapeutics, a specialist in rare metabolic disease.
One-of-a-Kind ‘Accès Précoce’
At the centrepiece of France’s rare disease leadership has been a much-celebrated early access pathway, supported by dedicated funding, that has enabled French patients to become among the first in the world to access breakthrough medicine.
“Historically, France has been associated with lengthy delays in patient access, combined with relatively low prices and high volumes. However, in the field of rare diseases, the framework established through the National Rare Disease Plans has introduced an unprecedented level of flexibility,” Recordati’s Jean-Claude Roche observes.
“Early access and compassionate use programmes allow patients to receive treatment rapidly, even when data are not yet fully consolidated, provided there is a clear unmet need. This represents one of the most remarkable and conspicuous strengths of the French setup,” he affirms.
Nienke Feenstra, general manager at Japanese biopharma, Takeda, very much concurs. “The country’s Early Access (Accès Précoce) for ‘presumed’ innovative drugs treating serious and rare diseases in instances where there is a therapeutic vacuum and thus no alternative treatments available is what makes France profoundly special and sets it apart from other markets, because it enables patients in need to get their hands on innovation sooner which can be a gamechanger for these types of complex and weighty disorders,” he insists.
Others speak warmly of the immense benefits that such a mechanism has unlocked. “Alexion has made a point of utilising this pathway whenever appropriate because it allows patients to receive treatment considerably sooner than the standard regulatory sequence would ever permit. Over the past two years, for three recently launched indications, we calculate that this regulatory flexibility has produced roughly 1,400 additional patient-days of access. In rare diseases, where time often shapes outcomes, this makes a meaningful difference,” recalls Khalife.
argenx’s Francois Rauch, for his part, recounts how the mechanism enabled his firm to make its treatments available at the same time as progressing regulatory, pricing and organisational steps. “Our first launch involved an injectable therapy administered in the hospital setting, which can be tricky. Managing everything in parallel required careful judgement on timing and risk, yet it ensured patients received relief in an expedited manner, even while we were still in the process of establishing the affiliate,” he remembers.
Some market insiders, however, sense a recent determination on the part of the authorities to tighten the rules and become more selective. “Early authorisation is never guaranteed and increasingly depends upon rigorous assessments from the regulator and health technology assessment (HTA) apparatus,” warns Kyowa Kirin’s Aurélie-Anne Chausse. “Even when granted, companies must commit to detailed evidence generation in the form of structured real-world data collection through case-report-style forms that can place a real burden on clinicians in routine practice,” she reminds.
The significance of this became more pronounced with the unveiling of the 2026 Social Security Financing Bill (PLFSS 2026) which, for the first time, empowered France’s HTA body, the Haute Autorité de Santé (HAS), to terminate Early Access if a manufacturer fails to provide rigorous real-world data within the first six months. “It appears that fewer medicines are being accepted into early access nowadays than in the past, and that those that are being given the green light tend to be supported by strong data and address areas of genuine unmet need,” observes Franck Cousserans, general manager for France and the Benelux at Jazz Pharmaceuticals. “Personally, however, I feel that this selectivity strengthens the credibility of the system rather than weakening it,” he remarks.
Others are more wary about any tinkering with a process that has worked so well for so long. “The Accès Précoce is a tried and tested mechanism that has already successfully provided early access to more than 100,000 patients, so safeguarding it is an absolute must if we are to preserve French leadership in the rare disease space,” argues AstraZeneca’s President Anne-Laure Dreno. “There is a persistent misconception that Early Access represents some kind of financial burden for the State. Whereas, in actual fact, at the end of the negotiation process, companies refund all payments made during the early access period at the final price agreed with the Comité Économique des Produits de Santé (CEPS), the national pricing authority, making the system essentially cost-neutral,” she opines.
Tough Decisions
The real bottlenecks tend to arise, however, when next-generation rare disease therapies enter formal assessment and pricing negotiations. “The framework is not yet adapted to the characteristics of rare diseases, where small populations, rapid disease progression and ethical constraints prevent large, long-term placebo-controlled trials,” notes Biogen’s Marina Vasiliou. “Though dialogues with the HAS and the CEPS are constructive, their criteria still rely on thresholds that ultra-rare conditions cannot realistically meet,” she warns.
“Basically, the current evaluation frameworks have been designed for common diseases. In rare conditions, where populations are small and the standard primary endpoints are not always the most relevant, a broader and more clinically nuanced perspective is going to be required, including the consideration of secondary outcomes,” elaborates Amicus’ Caroline Yau.
Dominique Bery, general manager at Ipsen, perceives that there is evidence of increasing acknowledgement, at the level of the HAS, that rare disease therapies will reach the system with immature data or without comparative data, and that they still deserve to be reimbursed. “Nonetheless, these drugs will still often receive an assessment that will not enable the CEPS to grant them an acceptable pricing given the investments that came into their development,” he bemoans.
“Drug developers should really be granted a certain additional timeframe to gather extra data to strengthen the clinical evidence, for instance, working in collaboration with scientific societies to set up robust registries,” he recommends.
“Moreover, the authorities should consider balancing price with volume-based tools, which can create a more favourable environment for high-innovation medicines aimed at small patient populations,” he suggests, pointing out that net prices for rare disease therapies in France remain well below the European median.
Others report encountering difficulties in negotiating acceptable reimbursement. “Amicus was prepared to introduce our Pombiliti + Opfolda innovative therapy for late onset Pompe disease but, despite our best efforts, we were simply not able to reach an agreement with the authorities,” regrets Caroline Yau. “In the past, even when negotiations were difficult, there was usually a way forward, whether through price adjustments or restricted access for a limited number of patients. However, over the past two years, that room for compromise seems to have all but disappeared,” she confides.
“Looking ahead at the future for our sector, the question will be not so much about redefining priorities but about sustaining them in an environment with significant financial pressure. Funding will determine how far the best formulated plans can go,” concludes Celine Khalife.
