FDA Approves First Gene Therapy Treatment for Wiskott-Aldrich Syndrome

The U.S. Food and Drug Administration has approved Waskyra (etuvetidigene autotemcel), the first cell-based gene therapy for the treatment of Wiskott-Aldrich syndrome (WAS). Waskyra is indicated for pediatric patients six months and older and adults with WAS who have a mutation in the WAS gene and for whom hematopoietic stem cell transplantation (HSCT) is appropriate and no suitable human leukocyte antigen (HLA)-matched related stem cell donor is available.

“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, M.D., M.P.H., Chief Medical and Scientific Officer and Director of the FDA’s Center for Biologics Evaluation and Research. “The FDA 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.”

WAS is a rare, life-threatening genetic disease caused by mutations in the WAS gene. The condition is characterized by bleeding, eczema, recurrent infections, and increased susceptibility to autoimmunity and lymphoreticular malignancies. Until today, treatment options for patients with WAS have been limited to symptomatic management and allogeneic hematopoietic stem cell transplantation, with the latter being most effective when performed early in life and feasible only when matched donors are available.

Waskyra consists of the patient’s own hematopoietic (blood) stem cells (HSCs), which have been genetically modified to include functional copies of the WAS gene. Following reduced-intensity conditioning, the gene-corrected cells are infused intravenously to restore blood cell production. Waskyra restores functional WAS protein expression in affected cells, addressing the underlying cause of the disease.

The safety and effectiveness of Waskyra was assessed based on two open-label, single-arm, multinational clinical studies and an expanded access program totaling 27 patients with severe WAS, which demonstrate substantial and sustained clinical benefit for patients with severe WAS, with significant reductions in the primary disease manifestations that drive morbidity and mortality.

The rate of severe infections decreased by 93% in the six to 18 months post-treatment period compared to the rate 12 months before treatment. Similarly, moderate and severe bleeding events were reduced by 60% in the first 12 months post-treatment compared to the year prior to treatment. Most patients did not report moderate to severe bleeding after four 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,” said Vijay Kumar, M.D., Acting Director of the CBER Office of Therapeutic Products. “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 side effects associated with Waskyra include rash, respiratory tract infection, febrile neutropenia, catheter related infection, vomiting, diarrhea, liver injury, and petechiae.

During the review of Waskyra, the FDA exercised appropriate regulatory flexibility across four critical areas: rare disease considerations, clinical trial design, mechanism of action, and chemistry, manufacturing and controls (CMC). This enabled approval and timely access to the product for this serious, life-threatening disease while carefully balancing pre-approval data requirements with post-market commitments. The FDA permitted the use of relevant manufacturing and quality data submitted to this BLA from a similar, approved product that was justified to be adequately representative of Waskyra for these purposes.

The application was granted Orphan Drug, Rare Pediatric Disease, and Regenerative Medicine Advanced Therapy designations.

The FDA granted approval of Waskyra to Fondazione Telethon ETS. This is a first approved cell and gene therapy product from a non-profit applicant.