France has long been held up as Europe’s reference point for rare disease care – the first EU country with a national plan, a pioneer of coordinated expert networks, and home to some of the continent’s most influential patient organisations. More than three million French citizens live with one of 7,000 rare diseases, most of them genetic and often disproportionately affecting young children.
Two decades after its first national plan, and with a new plan up to 2030 now launched, the question is no longer whether France is a leader, but whether its model can keep pace with rising expectations, scientific breakthroughs and mounting economic pressures.
Networked In
To identify and treat rare diseases – which by their nature affect small patient populations and are often little-studied and understood – France has attempted to pool its healthcare resources. Most significantly, PNMR1 established 23 different disease groups for rare diseases in France, each supported by a network of expert centres, which enable patients to access multiple specialists in the same location, often on the same day.
The French network model has subsequently been adopted across Europe in the form of European Reference Networks (ERNs), which allow experts from different countries and regions to communicate and collaborate.
“France’s network of reference and competence centres ensures that expertise is concentrated rather than diluted, allowing patients to be diagnosed and treated more effectively,” explains Jean-Claude Roche, France general manager for Recordati Rare Diseases, a subsidiary of the Italian Recordati Group, which bases both its European headquarters and a significant manufacturing footprint in France.
“Once patients are diagnosed, the French ecosystem performs remarkably well, with reference centres offering clear pathways, structured coordination, and close collaboration between specialists,” confirms Corinne Blachier-Poisson, the France GM of Amgen, which entered the rare disease field with the 2023 acquisition of Horizon Therapeutics.
However, the system is far from perfect, with French rare disease patients facing many of the same issues as their counterparts in other countries. “The principal challenge remains diagnosis,” warns Blachier-Poisson, “patients often wait an average of eight years before their condition is correctly identified.”
Databases & Registries
The digital infrastructure necessary to better identify, treat and monitor rare diseases has also advanced significantly, with a national database, the Base Nationale de Données Maladies Rares (BNDMR), capturing core data on patients with rare diseases across France. “Although issues of interoperability and data linkage persist, progress is steady, and each year the system becomes more capable of driving discovery, fostering innovation, and enabling early access to treatments,” says Roche.
French data is already being fed back into the system to drive the next wave of rare disease innovation. “Our institute’s connection to more than 30 reference centres for rare diseases in France creates unprecedented access to patient cohorts and clinical data,” says Bana Jabri, the recently appointed director of genetic research institute, Institut Imagine. “This infrastructure provides the foundation for translating genetic discoveries into therapeutic applications.”
Just one example of how this data goldmine is being used comes from SACHA, a national observational registry supported by the French association ‘Imagine for Margo’ and managed by oncology centre Gustave Roussy in partnership with the French Society of Paediatric Oncology (SFCE). SACHA gathers real-world safety and efficacy data on therapies prescribed to children, adolescents, and young adults who are not eligible for clinical trials.
“SACHA was pivotal in the development of Qarziba, our treatment of neuroblastoma,” explains Roche. “Although neuroblastoma is one of the tumours covered, the registry is broader in scope and offers valuable insight into off-label or compassionate use, helping clinicians and health authorities to assess how treatments perform outside controlled studies.”
Unified Patient Advocacy
Then there are the country’s well-organised and united patient advocacy groups, which have been instrumental in bringing about many of France’s pioneering rare disease policies. Chief among these groups is the French Muscular Dystrophy Association (AFM-Telethon), established in 1958 and key to the creation of both PNMR1 and all that has followed since.
“To be direct: most elements of the rare disease ecosystem in France were initiated by AFM,” proclaims the group’s vice president, Francois Lamy, himself the father of a child with the rare condition Duchenne muscular dystrophy.
“From the very first Téléthon in 1987 [a fundraising event that generates EUR 90 million annually – Ed.], a fundamental principle has guided our approach: fragmentation serves no one. We understood that if each rare disease created its own organisation and collected modest sums independently, we would accomplish nothing beyond communication expenses.”
To this end, AFM-Telethon helped launch the French Rare Disease Alliance, as well as a European grouping – EURORDIS – enabling smaller organisations to access resources whilst providing a collective voice for advocacy with public authorities. “Two hundred associations possess no influence if they speak disparately; united, they become formidable,” states Lamy.
Rare & Genetic R&D Heritage
France is not just a frontrunner in rare disease diagnosis and treatment but is also making a major contribution to the development of new medicines. Given the fact that over 80 percent of rare diseases have a genetic component, much of the focus has been on gene therapies.
France holds a distinctive position in gene therapy, which Frederic Revah, CEO of Genethon explains, “is grounded in a long track record of scientific achievement and supported by an ecosystem that spans fundamental research, clinical translation and industrial scale biomanufacturing.”
Established by AFM-Telethon in 1990 as a non-profit research organisation dedicated to rare genetic diseases, Genethon has spent the past 35 years pursuing uncertain and technically demanding targets. 13 current clinical programmes draw from Genethon’s investigative work, which also contributed to the development of Zolgensma, the blockbuster first systemic gene therapy approved for spinal muscular atrophy (SMA), now marketed by Novartis.
“Early success at Hôpital Necker-Enfants Malades for children with X-linked severe combined immunodeficiency, led by Alain Fischer and Marina Cavazzana Calvo, remains a defining milestone in modern gene medicine and helped establish the clinical expertise that continues to anchor the field in France,” adds Revah. “Since then, the country has built a coherent environment for advanced therapies, with leading centres capable of running complex trials and facilities such as Yposkesi, which is now among the largest viral vector production sites in Europe.”
France’s leadership in rare and genetic disease research is also having an impact beyond rare conditions. “Our research on genetic mutations affecting receptors linked to Parkinson’s disease, for example, demonstrates how insights from monogenic disorders can illuminate pathways relevant to prevalent conditions,” says Institut Imagine’s Bana Jabri.
“Similarly, our work on telomere-related genetic disorders provides insights into ageing mechanisms with potential applications across multiple therapeutic areas,” adds Jabri, a world-renowned paediatrician and immunologist, who spent 25 years at some of the USA’s top research institutions before returning to her native France earlier this year.
Access & Pricing
On the regulatory front, France is generally a conducive environment for the approval of cutting-edge gene therapies for rare diseases. “The ANSM [Agence nationale de sécurité du médicament et des produits de santé – France’s national regulatory body – Ed.] and the European authorities provide a stable and pragmatic framework for advanced therapies, and several gene therapy products have been authorised in Europe before receiving clearance in the United States,” notes Genethon’s Revah.
“At a time when other regions are experiencing greater regulatory uncertainty or fluctuations in R&D investment, this predictability has become a competitive advantage.”
Many of these therapies have made it to patients in France under early access schemes, which allow for access much earlier than formal HTA timelines allow.
AAP (Autorisation d’Accès Précoce) is designed for medicines that show promising clinical benefit in serious or rare diseases and can be granted before or after EMA approval, while pricing is still under negotiation. It allows broad cohort access, full reimbursement and requires real-world data collection.
Meanwhile, AAC (Autorisation d’Accès Compassionnel) is for individual or very small groups of patients when no alternative exists and can include off-label use.
Recently announced reforms to these mechanisms could threaten the viability of launching innovative and high-cost rare disease treatments in France. “In rare diseases, France continues to be a priority market, largely thanks to its Early Access mechanisms, which remain highly valued and which we hope will be maintained,” says Nienke Feenstra, GM of Takeda France.
“France’s position ultimately depends on whether these early access routes can be used,” warns Feenstra. “If they are available, France can remain at the forefront of global launches. If not, the reality is that lengthy procedures, complex requirements, and protracted price negotiations will inevitably delay access, with other countries moving first.”
Providing access to innovation while also balancing budgets is especially challenging in rare diseases, where certain gene therapies (including the aforementioned Zolgensma) can run into the millions of euros for a single course of treatment. While recognising the important flexibility that France’s early and compassionate access schemes have granted companies like Recordati Rare Diseases, Roche adds that he is concerned about “the unpredictability of healthcare decisions and the lack of adequate value recognition in pricing.”
“Net prices for rare disease therapies in France remain well below the European median, which undermines the country’s attractiveness for sustaining long-term investment,” he adds.
For ultra-rare diseases, where only a handful of patients exist in a country the size of France, the situation is even more critical. “For those conditions, no viable economic model exists,” laments AFM-Telethon’s Lamy.
“We have even seen cases where a company secured regulatory approval in Europe yet could not obtain reimbursement in enough countries to sustain commercial supply. As a result, despite the product’s approval, European patients still cannot access it. From a patient’s perspective, that situation is simply unacceptable.”
Looking to 2030
Building on the achievements of previous national rare disease plans, in February, the French government announced PNRM4, to run from 2025 until 2030. A key goal of the Plan is to foster better access to specialised care across the country via 132 new reference centres for rare diseases. The Plan also includes a focus on early diagnosis and better care coordination; improved diagnosis through genetic testing; boosting innovation efforts, including through funnelling France 2030 funding towards rare disease research; and strengthening pan-European cooperation.
Not everyone feels the new Plan goes far enough. “The current plan lacks ambition,” states Lamy. “It largely repeats the previous plan without introducing real innovation. The continued focus on diagnostics, genetic platforms and high-throughput sequencing simply highlights that we have not yet achieved the goals set in the earlier plan and must keep pursuing them.” He continues, “Our main concern is the insufficient focus on therapies and innovative treatments. This is a major omission, particularly for ultra-rare diseases”
“For ultra-rare diseases, we advocate forcefully for public intervention – specifically, a national fund dedicated to financing compassionate use of treatments,” continues Lamy. “With such limited patient populations, demonstrating efficacy and safety through conventional clinical trials before treatment administration is impossible.”
Additionally, for researchers, operating under the auspices of such overarching national plans can also pose challenges. “Centralised coordination is essential for establishing common biobanks, standardised protocols, and shared databases,” says Institut Imagine’s Jabri. “However, excessive centralisation can stifle the flexibility and rapid decision-making that characterise breakthrough research.”
“Our approach emphasises collaborative autonomy; participating actively in national initiatives while maintaining the independence necessary for rapid technological adoption and strategic partnerships,” adds Jabri. “This requires sophisticated governance structures that balance collective objectives with institutional prerogatives.”
Regardless of the challenges, France’s rare disease ecosystem remains one of the most structured and mature in Europe, with deep scientific capacity, influential patient advocacy and a regulatory apparatus that has historically enabled early access to innovation. PNMR4 sets out an admirable path focused on diagnosis, coordination and research, but its long-term impact will hinge on whether France can resolve the tension between ambition and affordability.
