FDA approves first gene therapy for Wiskott-Aldrich syndrome

USA— The U.S. Food and Drug Administration (FDA) has approved Waskyra (etuvetidigene autotemcel), marking the first cell-based gene therapy for the treatment of Wiskott-Aldrich syndrome (WAS).

This rare, life-threatening genetic disorder results from mutations in the WAS gene and is characterized by bleeding, eczema, recurrent infections, and a higher risk of autoimmunity and cancer.

Waskyra is specifically indicated for pediatric patients aged six months and older, as well as adults diagnosed with WAS who have a mutation in the WAS gene.

It is intended for those for whom hematopoietic stem cell transplantation (HSCT) is suitable but who lack a compatible human leukocyte antigen (HLA)-matched related donor.

Dr. Vinay Prasad, M.D., M.P.H., Chief Medical and Scientific Officer and Director of the FDA’s Center for Biologics Evaluation and Research, described the approval as a transformative milestone for patients with Wiskott-Aldrich syndrome.

He emphasized that Waskyra represents the first FDA-approved gene therapy that uses a patient’s own genetically corrected hematopoietic stem cells to treat the underlying cause of the disease.

Dr. Prasad added that the FDA remains committed to maintaining regulatory flexibility for rare diseases by evaluating all available data sources, including evidence from expanded access programs, while ensuring that scientific standards are met.

Traditionally, treatment options for people with WAS have been limited to symptomatic management and allogeneic stem cell transplantation.

Although transplantation is highly effective when performed early in life, it has been restricted to patients who have a suitable donor match.

Waskyra changes this by using the patient’s own hematopoietic (blood) stem cells that are genetically modified to include functional copies of the WAS gene.

Following reduced-intensity conditioning, the corrected cells are infused intravenously to restore normal blood cell production and reestablish the expression of functional WAS protein in affected cells.

The FDA’s approval was supported by results from two open-label, single-arm, multinational clinical trials and an expanded access program involving 27 patients with severe WAS.

The findings demonstrated substantial and sustained clinical benefits, including a 93% reduction in severe infections during the six to 18 months after treatment compared with the 12 months before therapy.

In addition, moderate and severe bleeding events decreased by 60% within the first year following treatment, and most patients reported no significant bleeding four years after receiving the therapy.

Dr. Vijay Kumar, Acting Director of the CBER Office of Therapeutic Products, noted that the approval meets an urgent need in the WAS community, where patients have long endured a life of fear and uncertainty due to the lack of approved treatments.

He emphasized that the decision represents meaningful progress, giving affected individuals the opportunity to engage more confidently in daily life, including attending school or participating in sports.

The most common side effects associated with Waskyra include rash, respiratory tract infections, febrile neutropenia, catheter-related infections, vomiting, diarrhea, liver injury, and petechiae.

During the review process, the FDA applied regulatory flexibility across four key areas: rare disease considerations, clinical trial design, mechanism of action, and manufacturing controls.

This balanced approach helped ensure timely access to a life-saving therapy while upholding safety and quality standards.

To support the submission, the FDA accepted relevant manufacturing and quality data from a similar, previously approved product deemed representative of Waskyra’s production.

The therapy received Orphan Drug, Rare Pediatric Disease, and Regenerative Medicine Advanced Therapy designations, underscoring its significance in addressing critical unmet medical needs.

The FDA granted approval of Waskyra to Fondazione Telethon ETS, marking the first time a nonprofit organization has received authorization for a cell and gene therapy product.