FDA clears first gene therapy for rare genetic disease WAS

Fondazione Telethon ETS' Waskyra has become the first gene therapy in the US for patients with Wiskott-Aldrich syndrome (WAS), a rare and life-threatening inherited disease.

The Italian non-profit company's cell-based gene therapy has been cleared by the FDA for use in patients with WAS who are aged six months and older, are healthy enough to tolerate a haematopoietic stem cell transplant (HSCT), and have no matched donor available. It was recommended for a similar indication in the EU last month.

WAS is caused by mutations in the WAS gene and mainly affects boys, with an estimated incidence of 1 in 250,000 male births. Because people with the condition lack a functional WAS protein, their immune cells and blood cells do not develop and function normally, resulting in symptoms like bleeding, eczema, recurrent infections, and increased susceptibility to autoimmune conditions and certain cancers.

Waskyra (etuvetidigene autotemcel) consists of a patient's own haematopoietic stem cells (HSCs), which have been genetically modified to include functional copies of the WAS gene. After conditioning therapy to suppress the bone marrow, the gene-corrected cells are infused intravenously and engraft to restore blood cell production and the immune system.

The ex vivo gene therapy was developed through decades of research at the San Raffaele Telethon Institute for Gene Therapy (SR-Tiget) in Milan and, according to Fondazione Telethon chief executive Ilaria Villa, "confirms the value of a patient-centred model that turns research into real treatments, especially where the market fails to act."

The safety and effectiveness of Waskyra were tested in two open-label, single-arm clinical trials, along with an expanded access programme in 27 patients with severe WAS. The results showed "substantial and sustained clinical benefit" for patients with severe WAS, according to the FDA, with significant reductions in the primary disease manifestations.

That included a 93% reduction in severe infections in the six to 18-month period after the one-shot treatment compared to the 12 months before the procedure, along with a 60% fall in moderate and severe bleeding events in the first 12 months.

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

"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," commented Vijay Kumar, acting director of the Center for Biologics Evaluation and Research (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."

Photo by Sangharsh Lohakare on Unsplash