The European Medicines Agency (EMA) has recommended granting a marketing authorisation in the European Union (EU) for Waskyra (etuvetidigene autotemcel) to treat people aged six months and older with Wiskott-Aldrich Syndrome (WAS) who have a mutation in the WAS gene. Waskyra is used to treat patients for whom a Haematopoietic Stem Cell Transplantation (HSCT) is appropriate, but for whom no suitable stem cell donor is available.

WAS is a rare, inherited disease, seen almost exclusively in males, that affects blood cells and cells of the immune system (the body's natural defences). It is caused by abnormalities in the gene that produces the WAS protein found in blood cells and certain immune cells. Because people with the condition lack a functional WAS protein, their immune cells and blood cells do not develop and function normally.

People with WAS bruise and bleed easily because they have too few normal platelets (components that help the blood to clot); they also have frequent infections because they have too few normal immune cells, which could lead to sepsis (when bacteria and their toxins circulate in the blood and start damaging the organs). In addition, there is a higher risk of developing some types of cancer, such as lymphoma.

Patients with WAS who have a compatible donor are treated by HSCT. However, for most patients who have no compatible donor, there is an unmet medical need.

Waskyra is a gene therapy medicine that is made from stem cells (called CD34+ cells) that are collected from the patient’s blood. The cells are genetically modified in the laboratory so that they can produce a functional WAS protein. When transplanted back into the patient after a conditioning (preparatory) regimen, the modified cells migrate to the bone marrow where they start making healthy blood and immune cells that produce a functional WAS protein, thereby helping to relieve the symptoms of the disease. Waskyra is given only once, by infusion (drip) into a vein.

EMA’s recommendation is based on data from a clinical development programme involving a total of 27 patients with WAS. The main study was a single-arm clinical trial conducted in 10 children between one and nine years of age, supported by data from another clinical trial and an expanded access programme (including people treated via compassionate use and hospital exemption schemes) comprising a total of 17 patients between one and 35 years of age.

Overall, the data showed that the annualised rate of severe infections decreased from two events in the 12 months before treatment to 0.15 events in the one to two years post-Waskyra and to 0.12 events in the two to three years post-Waskyra. Similarly, the annualised rate of moderate and severe bleeding episodes decreased from 2.0 events in the 12 months before treatment to 0.16 events in the two to three years post-Waskyra.

The most common side effects reported in people treated with Waskyra were due to the procedures and medications required to receive the medicine such as the conditioning regimen and pre-treatment, and administration site conditions (infections related to the infusion device, bleeding at the catheter site).

In its overall assessment of the available data, the Committee for Advanced Therapies (CAT), EMA's expert committee for cell- and gene-based medicines, found that the benefits of Waskyra outweighed the possible risks in people with WAS requiring an HSCT for whom no suitable donor is available. The CHMP, EMA’s human medicines committee, agreed with the CAT’s assessment and positive opinion, and recommended approval of this medicine.

Waskyra was supported through an EMA pilot offering enhanced support to academic and non-profit developers of Advanced Therapy Medicinal Products (ATMPs) addressing unmet medical needs. Participants in the pilot, which is currently ongoing and includes two other medicines under development, could apply to receive enhanced support from EMA in navigating EU regulatory requirements and fee incentives for scientific advice, marketing authorisation application and pre-authorisation inspections.

The opinion adopted by the CHMP is an intermediary step on Waskyra’s path to patient access. The opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorisation. Once a marketing authorisation has been granted, decisions about price and reimbursement will take place at the level of each Member State, taking into account the potential role or use of this medicine in the context of the national health system of that country.