FDA Touts Flexibility in Approving First Gene Therapy for WAS

Rare Daily Staff

The U.S. Food and Drug Administration approved Fondazione Telethon ETS’ Waskyra, the first cell-based gene therapy for the treatment of the rare immune disorder Wiskott-Aldrich syndrome, and the first approved cell and gene therapy product from a nonprofit applicant.

Waskyra is indicated for pediatric patients six months and older and adults with Wiskott-Aldrich syndrome (WAS) who have a mutation in the WAS gene and for whom hematopoietic stem cell transplantation is appropriate and no suitable human leukocyte antigen–matched related stem cell donor is available.

WAS is a life-threatening genetic disease 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 a patient’s own blood stem cells, 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 application was granted orphan drug, rare pediatric disease, and regenerative medicine advanced therapy designations.

The safety and effectiveness of Waskyra were assessed based on two open-label, single-arm, multinational clinical studies and an expanded access program totaling 27 patients with severe WAS. The results demonstrated 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 percent in the six- to 18-month post-treatment period compared with the rate 12 months before treatment. Similarly, moderate and severe bleeding events were reduced by 60 percent in the first 12 months post-treatment compared with the year prior to treatment. Most patients did not report moderate to severe bleeding after four years post-treatment.

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 agency said it exercised appropriate regulatory flexibility across four critical areas: rare disease considerations, clinical trial design, mechanism of action, and chemistry, manufacturing, and controls. 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.

“Today’s approval is a transformative milestone for patients with Wiskott-Aldrich syndrome, offering the first FDA-approved gene therapy that uses a patient’s own genetically corrected hematopoietic stem cells to treat the disease,” said Vinay Prasad, director of the FDA’s Center for Biologics Evaluation and Research. “The FDA continues to exercise flexibility in its 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.”

Photo: Vinay Prasad, director of the FDA’s Center for Biologics Evaluation and Research