The sustainability of gene therapies for rare diseases: a model born from ADA-SCID and WAS

Fondazione Telethon have obtained marketing authorisation for a gene therapy thanks to a sustainability model that integrates research with industry, patients and supporters. Read the full interview with Celeste Scotti, R&D Director at Fondazione Telethon.

In recent months, gene therapy for Wiskott–Aldrich syndrome (WAS) has received a positive opinion from both the EMA’s CHMP for the European market and the FDA for commercialisation in the United States. This represents a major milestone for patients, particularly for those who are unable to undergo haematopoietic stem cell transplantation—currently the standard first-line treatment—because a compatible donor is unavailable or because of limitations related to chemotherapy tolerability.

The path leading a medicinal product to marketing authorisation requires expertise, functions and infrastructures that are markedly different from those of academic preclinical and clinical research. It is therefore clear how essential a coordinated and collective effort is, involving researchers, clinicians, regulatory specialists and, crucially, stakeholders and funders.

Fondazione Telethon is the first non-profit organisation to have obtained marketing authorisation for a gene therapy—first for ADA-SCID and now for WAS—thanks to a sustainability model that integrates research, carried out at SR-TIGET, with industry, patients and supporters.

Any therapy—not only gene therapy—must be sustainable for all the actors involved: the organisation and the company developing it, as well as the healthcare systems, whether public or private, that are ultimately responsible for ensuring patient access. This makes it essential to consider the economic and financial dimensions of developing, manufacturing and commercialising gene therapies for rare and ultra-rare diseases.

Overall, the development of a therapy across all stages—from preclinical research to commercial launch—requires, on average, around €3 billion. While costs are lower for rare diseases, they still amount to hundreds of millions of euros. Moreover, revenues generated by therapies that do reach the market must cover not only the costs of successful products, but also the entire research and development pipeline, including approaches that ultimately fail. Pharmaceutical companies must also factor in the need to generate a return on investment—an objective that becomes extremely challenging in the context of rare and ultra-rare diseases, where patient populations are inevitably small.

Fondazione Telethon finances both research and the regulatory pathway towards market authorisation for gene therapies through donations and other funding mechanisms. As a non-profit organisation, it does not need to generate profits or distribute dividends. At the same time, however, it is crucial that the long-term maintenance of a therapy does not operate at a loss, as this would inevitably divert resources away from basic research.

As Celeste Scotti, R&D Director at Fondazione Telethon, explains: “The commercialisation and long-term maintenance of gene therapy for WAS must be self-sustaining; any surplus, should it exist, would be reinvested in research—a field to which we have increased our commitment in recent years.”

To ensure the sustainability of gene therapies for rare diseases—such as ADA-SCID and WAS, as well as future indications—this system must be underpinned by strong partnerships with pharmaceutical companies, start-ups, donors, stakeholders, patients, investment funds, and by effective dialogue with regulatory authorities and healthcare systems.

In today’s biomedical research landscape, investors tend to focus on projects that are already at an advanced stage, stepping in only once a therapy has demonstrated initial validation in patients. Capital typically flows in when the risk of failure has been substantially reduced. While this approach is understandable from a financial sustainability perspective, it leaves the earliest phases of therapeutic development—the most complex, costly and uncertain—largely uncovered.

It is precisely in this gap that Fondazione Telethon takes responsibility for the early and intermediate stages of therapeutic development, advancing programmes until they become mature, validated and therefore attractive to industrial partners or investors. The search for funding and corporate partnerships thus takes place once most of the scientific and developmental work has already been completed: for companies, this means acquiring a therapy that is essentially ready for the market, while the costs and risks of the earlier stages have largely been absorbed by Fondazione Telethon.

When, during this phase, interested partners come forward, the Foundation facilitates the transfer of the project. When the market does not respond, however, it continues development independently, with the primary objective of ensuring patient access to treatments that would otherwise be unlikely to reach the clinic, as was the case with gene therapy for WAS.

As Celeste Scotti explains: “Industry involvement becomes appropriate when we have a therapeutic approach that is already mature and functional, built on consolidated platforms, supported by robust scientific evidence, and with potential applications not only in ultra-rare diseases but, in some cases, also in rarer conditions with higher prevalence. This makes therapies more attractive to industry and broadens the number of potential beneficiaries.”

In a field where economic sustainability represents a structural challenge, this model enables the Foundation to attract partners and investors while at the same time strengthening its role as a bridge between academic research and clinical application. Fondazione Telethon is increasingly positioning itself as an actor capable of ensuring continuity of development precisely at those points where industry alone cannot—or does not—intervene.

To support this new model, Fondazione Telethon has had to develop new capabilities.
Its Research and Development area has been structured as a non-profit incubator within the Foundation, incorporating many of the functions typically found in industry.

As a result, Fondazione Telethon has positioned itself as a hub for the development of orphan drugs, particularly in areas where industry struggles to identify a financially sustainable model of engagement.

Fondazione Telethon’s model does not stand on its own. Despite the financial advantage of not being required to generate profits, it cannot afford to operate at a loss, nor does it wish to divert resources away from research. For this reason, the concept—emphasised by Celeste Scotti—of addressing unmet therapeutic needs through the creation of synergies and partnerships is fundamental.

In terms of funding, Fondazione Telethon relies first and foremost on the crucial role of donors, who make a substantial contribution to the costs of research. Public funding has also played a key role: within the framework of Italy’s National Recovery and Resilience Plan (PNRR), dedicated resources have enabled the development of advanced therapies, particularly through collaborations with other Italian institutions such as Bambino Gesù Children’s Hospital in Rome and the Tettamanti Foundation for the study and treatment of childhood leukaemia, part of IRCCS San Gerardo.

At the private level, many gene therapies are manufactured by commercial companies—such as AGC Biologics—which support Fondazione Telethon by recognising its non-profit status and engaging in sustainable and effective partnerships.

Patient organisations also play a critical role in strategic and regulatory decision-making. The Wiskott–Aldrich Foundation, for example, collaborated in the development of the gene therapy for Wiskott–Aldrich syndrome, facilitating interactions with regulatory authorities. As Scotti explains, “It is essential that the clinical development plan is validated by patient organisations, so that it reflects not only what regulators require, but also what truly matters to patients.”

At this time of transformation, Fondazione Telethon is looking beyond national borders, recognising that patients are everywhere. Treatments are currently administered in Milan and Naples, but the development of new gene therapies will require an expansion of partnerships and an increase in the number of treatment centres at both European and international level.
“In the United Kingdom we are in contact with a centre in London, while in the United States, following the approval process for the gene therapy for Wiskott–Aldrich syndrome, it will be necessary to ensure access for US patients as well. An Italian organisation cannot directly manage distribution in the United States and must rely on a local legal entity,” Scotti notes.

From a regulatory perspective, for the gene therapy for Wiskott–Aldrich syndrome, Fondazione Telethon was selected by the EMA to participate in a pilot programme dedicated to projects developed in academic settings. The initiative aims to improve communication between developers and regulatory authorities, enabling timely and structured scientific dialogue and offering support to academic organisations in addressing complex regulatory challenges.
The relationship with the FDA has also proved constructive: both agencies have shown openness and close attention to the work carried out, fostering an effective collaboration that Telethon hopes to continue in future projects.

The goal for the coming years is to ensure continuity for the gene therapies already available for ADA-SCID and Wiskott–Aldrich syndrome, guaranteeing their presence on the market and sustained patient access. For the therapy targeting Wiskott–Aldrich syndrome, an expansion of geographical approvals is planned, with the intention of making the treatment available not only in Europe, but also in the United States, the United Kingdom, and regions such as the Middle East, where the prevalence of rare diseases is significant.

At the same time, the Foundation is working to expand its development portfolio. A number of therapeutic programmes—both at clinical and preclinical stage—are currently underway and will continue to progress over the coming years.

This strategy therefore follows two complementary directions: the geographical expansion of existing therapies and the progressive increase in the number of therapeutic solutions available. The overarching objective is to help bridge the gap in the development of treatments for rare and ultra-rare diseases, a field in which commercial sustainability often represents a major barrier.