The US FDA has approved the first ever cell-based gene therapy to treat Wiskott-Aldrich syndrome (WAS).
The gene therapy, Waskyra (etuvetidigene), can be used to treat adults with WAS who have a mutation in the WAS gene and who can have haematopoietic stem cell transplantation (HSCT), but who lack a suitable stem cell donor. It can also be used to treat children aged six months and older.
WAS is a rare genetic disease caused by mutations in the WAS gene. Patients with WAS suffer from bleeding, eczema and frequent infections. Before the FDA’s approval, WAS patients could often only manage, and not treat, their condition. The only treatment for WAS was HSCT, which was only possible with a suitable donor.
The gene therapy is made from the patient’s own haematopoietic (blood) stem cells (HSCs), which have been genetically modified to include functional copies of the WAS gene. The cells are then transfused back into the patient’s body. The gene therapy restores functional WAS protein expression in affected cells, addressing the underlying cause of the disease.
The safety and effectiveness of the gene therapy was assessed based on two open-label, single-arm, multinational clinical studies and an expanded access programme that included 27 patients with severe WAS, which demonstrate substantial and sustained clinical benefit for patients with severe WAS.
Vinay Prasad, chief medical and scientific officer and director of the FDA’s Center for Biologics Evaluation and Research (CBER), said: “[This] approval is a transformative milestone for patients with WAS, offering the first FDA-approved gene therapy that uses the patient’s own genetically-corrected haematopoietic stem cells to treat the disease.”
Multiple studies have assessed the safety and effectiveness of the gene therapy. They found that patients with severe WAS gained major benefits, such as a decrease in disease symptoms, which can lead to death. After six to 18 months of treatment, WAS patients were found to have 93% fewer infections, compared to 12 months before treatment
In the first 12 months after treatment, moderate and severe bleeding events were reduced by 60% compared to the year prior to treatment. In addition, after four years, most patients did not report instances of moderate or severe bleeding.
The most common side effects include rash, vomiting, diarrhoea, liver injury and infections.
Vijay Kumar, acting director of the CBER Office of Therapeutic Products, said: “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.”