EU Moves Toward First Gene Therapy for Wiskott-Aldrich Syndrome
The European Medicines Agency (EMA) has recommended granting marketing authorization in the European Union for Waskyra (etuvetidigene autotemcel), a gene therapy designed to treat people aged 6 months and older with Wiskott-Aldrich syndrome (WAS) who carry mutations in the WAS gene. If approved, Waskyra would become the first approved gene therapy specifically targeting WAS, a rare and often life-threatening immunodeficiency.
What is WAS and how does Waskyra work?
Wiskott-Aldrich syndrome is a genetic disorder that affects the immune system and blood cells, leading to increased infections, bleeding, and a higher risk of autoimmune complications. The disease stems from mutations in the WAS gene, which encodes a protein essential for proper blood cell function. Traditional treatments focus on managing symptoms and complications, with hematopoietic stem cell transplantation (HSCT) as a potentially curative option in carefully selected patients. Waskyra offers a different approach: a patient’s own hematopoietic stem cells are collected, genetically modified to correct the WAS gene, and then reintroduced. This autologous gene therapy aims to restore normal WAS protein function and improve immune competence while reducing the risks associated with allogeneic transplantation, such as graft-versus-host disease.
Clinical evidence and who may benefit
Regulators evaluated data from clinical studies that examined the safety and efficacy of etuvetidigene autotemcel in children and infants with WAS. Key questions included whether the therapy can reliably introduce a functional WAS gene variant into a patient’s stem cells and whether in vivo immune function improves as a result. The EMA’s recommendation reflects a favorable balance of benefit over risk in the studied population, particularly for patients who lack a matched donor for HSCT or who face significant complications from standard therapies. As with any gene therapy, patient selection, timing of treatment, and the management of potential adverse events remain critical to outcomes.
Potential benefits
- Restoration of immune function and reduced susceptibility to infections.
- Improved platelet counts and decreased bleeding risk.
- Elimination of the need for donor-derived transplants in eligible patients.
Possible risks and monitoring
- Risks associated with gene modification procedures and conditioning regimens used to prepare the patient’s body for infusion.
- Uncertainties about long-term durability and potential off-target effects.
- The necessity for long-term follow-up in specialized centers to monitor immune reconstitution and hematologic health.
Where Waskyra fits into current WAS care
For families and clinicians, Waskyra represents a potential paradigm shift in WAS management. It aligns with a growing trend toward autologous gene therapies that aim to correct the underlying genetic defect while preserving the patient’s own cells. If authorized, Waskyra would likely be available through reference centers with expertise in rare immunodeficiencies and gene therapy delivery, ensuring that patients receive comprehensive care before, during, and after treatment.
What comes next
The EMA’s recommendation usually leads to a formal marketing authorization decision by the European Commission. Once approved, member states will begin the process of integrating Waskyra into national health systems, including pricing, reimbursement negotiations, and patient access pathways. Given the rarity of WAS, continued post-marketing surveillance and patient registries will be important to track long-term outcomes and inform future practice.
Implications for other gene therapies and rare diseases
Waskyra’s potential approval highlights the accelerating pace of gene therapy development for rare diseases. Success in WAS could influence regulatory thinking and encourage further investment in autologous gene-modification strategies, offering new hope to patients with conditions that have historically lacked effective curative options. It also underscores the need for robust infrastructure and expertise to deliver complex therapies safely and equitably across the EU.
