FDA Approves First Cell-Based Therapy Waskyra for Rare WAS Immunodeficiency

The U.S. Food and Drug Administration has approved Waskyra (etuvetidigene autotemcel), the first cell-based gene therapy for Wiskott-Aldrich syndrome (WAS), a rare and life-threatening immunodeficiency. The therapy is indicated for pediatric patients six months and older and adults with a confirmed WAS gene mutation who are candidates for hematopoietic stem cell transplantation but lack a suitable HLA-matched related donor.

The approval is the result of more than two decades of research at the San Raffaele Telethon Institute for Gene Therapy (SR-Tiget) in Milan. Reflecting on the milestone, 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.”

Dr. Alessandro Aiuti, Deputy Director of Clinical Research at SR-Tiget and Chief of Pediatric Immunohematology at IRCCS Ospedale San Raffaele, said, “The approval of this gene therapy represents a decisive step forward and a tangible response to the needs of patients. Seeing years of scientific research and dedication translate into real therapeutic opportunities gives profound meaning to our work.”

Understanding Wiskott – Aldrich syndrome (WAS)

WAS is a rare X-linked blood disorder caused by mutations in the WAS gene. The condition leads to immunodeficiency, low platelet counts and eczema, typically presenting in early childhood. Patients face recurrent infections, bleeding episodes and increased risk of autoimmune disease and lymphomas, often resulting in lifelong medical vulnerability.

Clinical Study Overview

The FDA approval is supported by a multicenter, open-label study evaluating ex vivo–modified autologous CD34+ hematopoietic stem cells. These cells were transduced with a lentiviral vector encoding the human WAS gene and infused following myeloablative conditioning. Participants included both pediatric and adult patients experiencing the classical complications of WAS, such as recurrent infections and bleeding.

Key Clinical Findings

Waskyra produced meaningful and sustained clinical benefit across immune function, bleeding risk and hematopoietic recovery.

Immune Reconstitution

Patients demonstrated improved immune restoration, with T- and B-cell recovery trending toward normal physiological ranges in most individuals. This translated into a 93 percent reduction in severe infections during the six to eighteen months after treatment compared with the year prior, along with fewer hospitalizations, reflecting meaningful immune reconstitution.

Platelet Counts and Bleeding

Thrombocytopenia has long been a major challenge in WAS management. Many treated patients experienced meaningful increases in platelet counts. Moderate and severe bleeding events decreased by 60 percent in the first year after treatment, and most patients reported no moderate or severe bleeding by year four, reducing the need for transfusions and improving long-term clinical stability.

Durability of Response

Long-term follow-up confirmed stable engraftment of gene-corrected cells and persistent expression of the Wiskott-Aldrich syndrome protein (WASp) for at least two to three years after treatment. These findings support durable gene correction and hematopoietic recovery. No cases of insertional oncogenesis or replication-competent lentivirus were reported.

Safety

No cases of insertional oncogenesis or replication-competent lentivirus were reported. The most common adverse events were related to myeloablative conditioning, including cytopenias and febrile neutropenia, and were manageable with standard care.

Vinay Prasad, M.D., M.P.H., Chief Medical and Scientific Officer and Director of the FDA’s CBER, noted: “Today’s approval is a transformative milestone for patients with Wiskott-Aldrich syndrome, offering the first FDA-approved gene therapy that uses the patient’s own genetically corrected hematopoietic stem cells to treat the disease.”

Adding to the patient-impact context, Vijay Kumar, M.D., Acting Director of the CBER Office of Therapeutic Products, stated: “Today’s approval addresses the urgent need in the WAS community, where patients have described living ‘a life of terrifying worry and fear’ without any approved therapies available.”

As with all gene therapies, recipients of Waskyra will be followed for 15 years to monitor long-term safety and sustained therapeutic benefit.

Significance

 Waskyra represents a major advancement for patients who lack a suitable donor for allogeneic stem cell transplantation. The approval reinforces the potential of autologous ex vivo gene correction to deliver lasting, disease-modifying outcomes in rare genetic immunodeficiencies.