FDA Approves Waskyra as First Gene Therapy for Wiskott-Aldrich Syndrome

The FDA has approved etuvetidigene autotemcel (Waskyra; Fondazione Telethon ETS) as the first cell-based gene therapy approved for the treatment of Wiskott-Aldrich syndrome (WAS).^1,2 Its indication is specifically for pediatric patients aged 6 months and older and adults with a mutation in the WAS gene for whom hematopoietic stem cell transplantation (HSCT) is appropriate but a suitable HLA-matched related donor is unavailable.

The approval marks a milestone for the treatment landscape of WAS, a rare, life-threatening, X-linked primary immunodeficiency characterized by thrombocytopenia, recurrent infections, eczema, autoimmunity, and elevated risk for hematologic malignancies. Historically, therapeutic options have been limited to supportive care and allogeneic HSCT, the latter of which is most successful when performed early in life and with a fully matched sibling donor—a scenario unfortunately unavailable to many patients.

“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,” Vinay Prasad, MD, MPH, the chief medical and scientific officer and director of the FDA Center for Biologics Evaluation and Research, said in a statement.

Alessandro Aiuti, MD, PhD, deputy director of clinical research at SR-Tiget, the chief of pediatric immunohematology at IRCCS Ospedale San Raffaele, and a full professor of pediatrics at Università Vita-Salute San Raffaele, said in a statement that the approval “represents a decisive step forward and a tangible response to the needs of patients,” and that “seeing years of scientific research and dedication translate into real therapeutic opportunities for people gives profound meaning to our work.”²

Waskyra Study Efficacy and Safety Findings

The safety and efficacy of Waskyra were demonstrated in 2 open-label, single-arm, multinational clinical studies as well as an expanded access program that collectively included 27 patients with severe WAS. Patients treated with Waskyra experienced substantial and sustained clinical benefits, including marked reductions in the key manifestations of the disease. Among the major findings from the clinical studies were the following:

• Severe infections were reduced by 93% during the 6- to 18-month post-treatment window compared with the 12 months prior to treatment.
• Moderate to severe bleeding events were reduced by 60% during the first 12 months after therapy.
• The majority of patients remained free from moderate or severe bleeding events 4 years post-treatment.

“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,” Vijay Kumar, MD, Acting Director of the CBER Office of Therapeutic Products, said in a statement.¹ “This action marks significant progress in the development of much-needed treatment options for patients affected by this debilitating and life-threatening disease, enabling them to engage in everyday activities such as going to school or participating in sports.”

The most common adverse events (AEs) reported with Waskyra in the clinical development program included rash, respiratory tract infection, febrile neutropenia, catheter-related infection, vomiting, diarrhea, liver injury, and petechiae. No unexpected safety signals were identified, and the benefit-risk profile was considered favorable given the seriousness of WAS and the lack of approved alternatives for many patients.

Waskyra’s Regulatory Review

Throughout the regulatory review of the gene therapy, the FDA applied flexible criteria to account for the rare and life-threatening nature of WAS. This included allowing supportive data from an expanded access program and the use of quality and manufacturing information submitted for a similar, approved gene therapy product, which was deemed representative of Waskyra. The agency highlighted 4 key areas of regulatory flexibility applied during the approval process: Rare disease considerations, including the use of expanded access data; clinical trial design, allowing single-arm studies in lieu of randomized trials; mechanism of action, leveraging known biology of WAS and gene therapy vectors; and chemistry, manufacturing, and controls (CMC), with appropriate comparability data accepted from an analogous product.

Prasad noted that the agency "continues to exercise flexibility in the regulatory approach for rare diseases by considering all available data sources, including, as appropriate, data from expanded access programs, to facilitate the advancement of life-changing treatments while ensuring scientific requirements are satisfied.”

How Does Waskyra Work?

Waskyra uses the patient’s own hematopoietic stem cells (HSCs), which then genetically modified ex vivo to express a functional WAS gene, and after reduced-intensity conditioning, the cells are infused back into the patient intravenously. The gene therapy is designed to restore WAS protein expression, ultimately correcting the underlying genetic issue and enabling restoration of immune function and platelet production.

All told, Waskyra offers a new treatment pathway for a vulnerable population of patients with limited treatment options. By enabling genetically corrected autologous stem cell therapy, the product could eliminate the need for lifelong supportive care or donor-dependent transplantation in eligible patients—a potential major step forward. Notably, it is also the first approved cell and gene therapy product from a nonprofit applicant to the FDA.

REFERENCES

1. FDA Approves First Gene Therapy Treatment for Wiskott-Aldrich Syndrome. FDA. December 9, 2025. Accessed December 10, 2025. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-treatment-wiskott-aldrich-syndrome
2. Fondazione Telethon Announces FDA approval of Waskyra™ (etuvetidigene autotemcel), a Gene Therapy for the Treatment of Wiskott-Aldrich Syndrome. Fondazione Telethon. December 9, 2025. Accessed December 10, 2025. http://fondazionetelethon.it/en/stories-and-news/news/from-telethon-foundation/fondazione-telethon-announces-fda-approval-of-waskyra-etuvetidigene-autotemcel-a-gene-therapy-for-the-treatment-of-wiskott-aldrich-syndrome/