WASKYRA Wins FDA Approval, Marking a Historic Leap for Rare Disease Gene Therapies

In a landmark decision on December 10, 2025, the FDA approved WASKYRA (etuvetidigene autotemcel), marking a transformative milestone in the treatment of Wiskott-Aldrich syndrome—a rare, life-threatening genetic blood disorder. This approval represents not only a significant advancement in gene therapy but also a historic achievement for the non-profit sector, as Fondazione Telethon became the first non-profit organization to successfully shepherd an ex vivo gene therapy from laboratory research through the complete regulatory pathway to FDA approval.

Wiskott-Aldrich syndrome is a rare genetic disorder caused by mutations in the WAS gene, which encodes a crucial protein that regulates white blood cell function and platelet maturation. This devastating condition affects almost exclusively males, with an estimated incidence of 1 in 250,000 live male births globally. The disease manifests early in childhood with a debilitating triad of symptoms: recurrent and persistent infections due to immune deficiency, recurring bleeding episodes stemming from low platelet counts, and chronic eczema.

Without a functional WAS protein, blood cells and immune cells do not develop and function normally, leaving affected individuals vulnerable to frequent and prolonged bleeding events, heightened infection risk, and a greater likelihood of developing autoimmune disorders and lymphomas. Until now, the primary treatment option has been hematopoietic stem cell transplantation (HSCT), which carries its own risks and is not always possible due to the difficulty of finding a suitable matched donor.

WASKYRA represents a paradigm shift in how WAS is treated. The therapy consists of a single therapeutic administration involving the patient’s own autologous CD34+ hematopoietic stem and progenitor cells. These cells are extracted from the patient’s bone marrow and then genetically modified outside the body using a lentiviral vector encoding the functional WAS gene.

The treatment process involves several coordinated steps. First, patients undergo peripheral blood mobilization with G-CSF (with or without plerixafor) followed by apheresis to collect stem cells. Subsequently, patients receive rituximab, an anti-CD20 monoclonal antibody, and undergo reduced-intensity conditioning chemotherapy to prepare their bone marrow to receive the corrected cells. Once the stem cells have been genetically corrected to produce functional WAS protein, they are reinfused back into the patient.

The FDA’s approval of WASKYRA was supported by compelling clinical data from two open-label, single-arm studies encompassing 27 patients with severe WAS. The results demonstrated substantial and sustained clinical benefit, with significant reductions in the primary disease manifestations.

The findings were striking. Severe infections dropped by an impressive 93% when comparing the period from six to eighteen months after treatment to the twelve months before WASKYRA administration. This represents a dramatic improvement in one of the most dangerous aspects of the disease. Additionally, patients experienced a 60% reduction in moderate and severe bleeding events, directly addressing another major manifestation of WAS.

These clinical outcomes underscore WASKYRA’s potential to fundamentally alter the trajectory of WAS patients, offering them the prospect of reduced hospitalizations, fewer infections, decreased bleeding episodes, and improved overall quality of life.

WASKYRA is indicated for the treatment of pediatric patients aged 6 months and older and adults with Wiskott-Aldrich syndrome who carry a mutation in the WAS gene. Importantly, the therapy is designed for eligible patients for whom hematopoietic stem cell transplantation is appropriate, but for whom no suitable HLA-matched related stem cell donor is available. This positioning fills a critical gap in the treatment landscape, offering hope to patients who would otherwise face limited therapeutic options.

During clinical trials, no adverse reactions were directly attributable to WASKYRA or the conditioning regimen. However, it is essential to note that treatment with WASKYRA involves multiple medical interventions beyond the gene therapy itself, including G-CSF mobilization, apheresis, rituximab pretreatment, and reduced-intensity conditioning—each carrying its own associated risks. Common side effects observed in patients included rashes, respiratory infection, and catheter-related infections.

The FDA underscores that when assessing the overall safety of WASKYRA treatment, clinicians must consider not only the gene therapy’s safety profile but also the safety profiles of all ancillary medications and procedures used during mobilization, pre-treatment, and conditioning phases.

The FDA’s approval represents a watershed moment for non-profit biomedical research. Fondazione Telethon, the Italy-based non-profit organization sponsoring WASKYRA, has successfully demonstrated that independent research organizations—not just traditional pharmaceutical companies—can navigate the complex drug development and regulatory landscape to bring life-saving therapies to patients.

Developed over decades of pioneering research at the San Raffaele Telethon Institute for Gene Therapy (SR-Tiget) in Milan, WASKYRA embodies the organization’s commitment to translating scientific discovery into clinical reality. This achievement is particularly noteworthy given that rare diseases often lack the commercial incentive to attract large pharmaceutical investments, making the work of dedicated non-profit organizations essential for advancing patient care.

As Ilaria Villa, CEO of Fondazione Telethon, stated, “The FDA’s approval of WASKYRA is an extraordinary achievement—not only for Italian research and for Fondazione Telethon, but for the global rare disease community. It confirms the value of a patient-centered model that turns research into real treatments, especially where the market fails to act.”

FDA Commissioner Marty Makary characterized WASKYRA’s approval as a “transformative milestone” for patients living with Wiskott-Aldrich syndrome, highlighting the significance of this breakthrough within the agency’s broader commitment to advancing therapeutic options for rare diseases.

The FDA approval follows a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use, received just weeks earlier, signaling international recognition of WASKYRA’s clinical value. This will facilitate access to the therapy for WAS patients globally by synchronizing approvals across major regulatory jurisdictions.

For patients and families affected by Wiskott-Aldrich syndrome, WASKYRA represents genuine hope. This transformative therapeutic option addresses a disease once considered virtually untreatable outside of the high-risk setting of stem cell transplantation. As gene therapy continues to evolve as a treatment modality, WASKYRA’s success demonstrates both the scientific potential of ex vivo gene therapy approaches and the vital role non-profit research organizations play in bringing these innovative treatments to those who need them most.