The Future of Advanced Therapies: Navigating Sustainability and Access for Ultra-Rare Diseases
Advanced therapies (ATMPs) – including gene and cell therapies – have revolutionized treatment possibilities for many rare and ultra-rare diseases, particularly in hematology, immunology, and metabolic disorders. However, regulatory approval doesn’t automatically translate to real, sustainable access for patients. A growing challenge is ensuring these potentially curative therapies remain available, especially when developed for conditions affecting very small patient populations.
The Commercial Sustainability Challenge
In Europe, the majority of authorized ATMPs have received orphan drug designation. Yet, a significant number have been withdrawn from the market due to commercial and sustainability concerns. Cases like Skysona and Zynteglo highlight how economic viability remains a major bottleneck. BioMarin Pharmaceutical’s recent voluntary withdrawal of valoctocogene roxaparvovec (Roctavian) for severe hemophilia A further underscores this issue.
This problem is particularly acute for ultra-rare diseases, where the number of treatable patients is extremely limited. The fixed costs associated with GMP manufacturing, pharmacovigilance, post-marketing obligations, and reimbursement negotiations often prove incompatible with traditional industrial models, even with regulatory incentives like orphan drug designation.
From Academia to Commercialization and Back Again
Many ATMPs for rare diseases originate in academic settings – hospitals, universities, and public research centers – often funded by public or philanthropic sources. These therapies are driven by unmet clinical needs rather than market logic. However, companies acquiring or further developing these therapies are increasingly deciding to halt commercialization due to economic unsustainability.
Strimvelis, a gene therapy for ADA-SCID developed at the Istituto San Raffaele Telethon for Gene Therapy in Milan, exemplifies this trend. Initially commercialized by GSK in 2016, responsibility transferred to Fondazione Telethon in 2022, preventing the loss of an effective, approved therapy. This represents a first-of-its-kind transfer and highlights the need for alternative models for therapies targeting very small populations. Fondazione Telethon also recently secured European authorization for a gene therapy for WAS.
Regulatory Efforts and Access Barriers
The European Union has introduced several measures to facilitate ATMP development, including dedicated scientific support for non-profit developers, EMA pilot programs for academia, and greater flexibility in study designs. However, the most significant difficulties arise after authorization, during access and reimbursement.
“One-shot” payment models, uncertainties surrounding long-term outcomes, and fragmentation of European healthcare systems complicate ensuring equitable and sustained access to advanced therapies. These limitations are even more pronounced for ultra-rare diseases.
The Need for Innovative Models
ATMPs for rare diseases cannot be evaluated solely using traditional market metrics. A coordinated effort is needed involving academia, industry, regulators, healthcare systems, and patient organizations. The future of these therapies hinges on building tailored development and access models where scientific innovation is coupled with organizational, regulatory, and economic innovation.
This requires a shift in thinking, recognizing that the value proposition of these therapies extends beyond conventional cost-effectiveness analyses. The potential for curative treatments, improved quality of life, and reduced long-term healthcare burdens must be factored into decision-making processes.
FAQ
Q: What are ATMPs?
A: Advanced Therapy Medicinal Products include gene therapies, cell therapies, and tissue-engineered products.
Q: Why are some ATMPs withdrawn from the market?
A: Primarily due to commercial and sustainability issues, particularly for ultra-rare diseases where the patient population is small.
Q: What is the role of academia in ATMP development?
A: Academia often drives initial research and clinical trials, but commercialization can be challenging without sustainable funding models.
Q: What is being done to improve access to ATMPs?
A: The EU is exploring recent regulatory pathways and payment models, but significant challenges remain.
Did you realize? Italy currently has 15 advanced therapies approved and reimbursed, with an estimated 13 more expected by 2027.
Pro Tip: Patient advocacy groups are playing an increasingly important role in advocating for access to ATMPs and raising awareness of the challenges faced by patients with rare diseases.
Explore more articles on Osservatorio Terapie Avanzate to stay informed about the latest developments in advanced therapies.
