The promise of curative therapies for rare and ultra-rare diseases is increasingly colliding with the realities of commercial sustainability. Advanced therapies – including gene and cell therapies – offer hope for conditions previously considered untreatable, yet a growing number are being withdrawn from the market despite demonstrating clinical efficacy. This disconnect, explored in a recent article in Blood ICT, highlights a fundamental flaw in the current pharmaceutical model when applied to conditions affecting extremely small patient populations.
These therapies, often born from academic research and fueled by public or philanthropic funding, represent a paradigm shift in medicine. But the high costs associated with manufacturing, ongoing monitoring, and securing reimbursement – even with orphan drug designation – are proving insurmountable for many companies. The result is a heartbreaking cycle of hope followed by disappointment for patients and families desperately seeking treatment.
The issue is particularly acute for ultra-rare diseases, where the number of potential patients is limited. According to data cited in the Blood ICT analysis, only about 5% of rare diseases currently have an approved therapy, leaving a significant “unmet need.” The financial burden of producing these highly personalized treatments, adhering to Good Manufacturing Practice (GMP) standards, and navigating complex regulatory pathways often outweighs the potential return on investment for traditional pharmaceutical companies.
This isn’t simply a matter of economics; it’s a question of access. The withdrawal of valoctocogene roxaparvovec (Roctavian), a gene therapy developed by BioMarin Pharmaceutical for severe hemophilia A, serves as a stark example. BioMarin announced the voluntary withdrawal of the drug in February 2026, despite its proven effectiveness, citing commercial challenges. Similarly, the cases of Skysona and Zynteglo, both gene therapies, were previously documented as being pulled from the market for economic reasons, demonstrating a concerning trend.
The Return to Academia: A Recent Model Emerges?
Interestingly, a growing number of these therapies are finding a lifeline through a “return to academia.” The story of Strimvelis, a gene therapy for ADA-SCID (Severe Combined Immunodeficiency due to Adenosine Deaminase Deficiency), illustrates this shift. Developed at the Istituto San Raffaele Telethon for Gene Therapy in Milan, Strimvelis was initially commercialized by GSK in 2016. However, after two years, Orchard Therapeutics took over, along with other advanced therapy programs. In 2022, Orchard Therapeutics stepped back, and Fondazione Telethon assumed responsibility for the marketing authorization of Strimvelis, preventing its disappearance from the market. This marked the first instance of such a transfer, and the foundation has continued this approach, securing European authorization for a gene therapy for Wiskott-Aldrich syndrome (WAS) in 2026.
This model, where non-profit organizations take on the stewardship of these therapies, suggests a potential solution for diseases affecting extremely small populations. The authors of the Blood ICT article argue that this isn’t an anomaly, but rather a signal that alternative development and access models are needed for advanced therapies targeting these niche patient groups. The trend of companies divesting from advanced gene therapy programs, even those with demonstrated clinical success, further underscores the urgency of finding sustainable solutions.
Navigating Regulatory Hurdles and Access Challenges
European regulatory bodies have taken steps to facilitate the development of advanced therapies, including dedicated scientific support for non-profit developers, pilot programs within the European Medicines Agency (EMA) for academic institutions, and increased flexibility in study designs. The recent introduction of the Joint Clinical Assessment within the European Health Technology Assessment (HTA) framework also aims to streamline the evaluation process. The EMA’s pilot program, for example, provides targeted support to academic developers.
However, the most significant obstacles arise *after* authorization, during the crucial phase of access and reimbursement. “One-shot” payment models, the uncertainty surrounding long-term outcomes, and the fragmented nature of European healthcare systems all contribute to difficulties in ensuring equitable and sustained access to these therapies. These challenges are amplified for ultra-rare diseases, where the cost-effectiveness arguments are particularly difficult to make.
A Call for Collaborative Innovation
The traditional market metrics simply don’t apply to advanced therapies for rare diseases. The Blood ICT article advocates for a critical re-evaluation of the current development and commercialization model. If the goal is to ensure equitable and lasting access to potentially curative therapies, a coordinated effort involving academia, industry, regulators, healthcare systems, and patient organizations is essential.
The future of advanced therapies hinges on the ability to create tailored development and access models. This requires a fusion of scientific innovation with organizational, regulatory, and economic innovation, fostering a continuous dialogue among all stakeholders. The work of Osservatorio Terapie Avanzate with the retreAT project exemplifies this collaborative approach, seeking to address these complex challenges.
The transformative potential of advanced therapies can only be fully realized when innovation translates into tangible and stable benefits for patients. This requires a fundamental shift in perspective, recognizing that these treatments represent not just a commercial opportunity, but a moral imperative.
Disclaimer: This article provides information for general knowledge and informational purposes only, and does not constitute medical advice. We see essential to consult with a qualified healthcare professional for any health concerns or before making any decisions related to your health or treatment.
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