Waskyra

Waskyra (etuvetidigene autotemcel) is a one-time, cell-based gene therapy for Wiskott–Aldrich syndrome (WAS), a rare inherited disease that can cause bleeding, eczema, recurrent infections, autoimmunity, and an increased risk of certain cancers. Patients with WAS have a mutation in the WAS gene that stops them from making functional WAS protein, so their immune and blood cells do not develop or function normally.

Waskyra is given as a single IV infusion made from the patient’s own hematopoietic (blood) stem cells, which are collected and genetically modified in the laboratory to include functional copies of the WAS gene. After infusion, these cells travel to the bone marrow and start producing healthy blood and immune cells that make functional WAS protein, helping to provide long-term relief from the symptoms of Wiskott–Aldrich syndrome.

Waskyra is an autologous cell-based gene therapy, autologous means the treatment is made specifically for you from your own cells.

The Waskyra treatment is a process that involves:

• Mobilisation and stem cell collection (apheresis)
• Gene modification in the laboratory
• Pretreatment and conditioning
• One-time Waskyra infusion
• Early recovery and engraftment

Waskyra FDA approval was granted on December 9, 2025; it is the first cell-based gene therapy for the treatment of Wiskott-Aldrich syndrome (WAS).

Waskyra is indicated for the treatment of Wiskott-Aldrich syndrome (WAS) in patients who are:

• Six months and older
• Have a mutation in the WAS gene, and
• Hematopoietic stem cell transplantation (HSCT) is appropriate, and
• No suitable human leukocyte antigen (HLA)-matched related stem cell donor is available.

In the clinical trial, Waskyra treatment led to a 93% reduction in severe infections within 6–18 months after treatment compared with the year before, and a 60% reduction in moderate and severe bleeding in the first 12 months post-treatment. Most patients had no moderate or severe bleeding events four years after treatment, suggesting sustained long-term benefit.

Waskyra treatment process

The Waskyra treatment is not just a single infusion; it’s a carefully planned process that happens in a specialist gene-therapy centre. While exact steps can vary by hospital, the process usually looks like this:

1. Mobilisation and stem cell collection (apheresis)

• Medicines are given to help move stem cells from the bone marrow into the bloodstream
• The cells are collected from the blood using a machine (a procedure called apheresis)
• These collected CD34+ hematopoietic stem cells are the starting material for Waskyra

2. Gene modification in the laboratory

The collected stem cells are then sent to a specialised lab where:

• A harmless, modified virus (a lentiviral vector) is used to deliver a working copy of the WAS gene into the cells
• The result is a batch of the patient’s own stem cells that now carry instructions to make functional WAS protein
• The product is carefully tested for quality and safety before it can be given back to the patient

3. Pretreatment and conditioning

Before receiving Waskyra, the patient has a conditioning regimen:

• Rituximab is administered approximately 22 days before Waskyra infusion
• Administer busulfan and fludarabine for reduced intensity conditioning before infusion of Waskyra to help engraftment of the genetically modified autologous CD34+ cells. and a reduced-intensity conditioning regimen of busulfan and fludarabine.

4. One-time Waskyra infusion

Once conditioning is complete and the Waskyra product is ready:

• To reduce the risk of allergic reaction, premedication of intravenous chlorpheniramine or an equivalent 15-30 minutes before the Waskyra infusion.
• The modified stem cells are given as a single intravenous (IV) infusion (a drip into a vein)

5. Early recovery and engraftment

After the infusion:

• The modified stem cells travel to the bone marrow and start to “engraft” – that is, they begin making new blood and immune cells
• Blood counts and infection signs are checked frequently
• Patients often stay in or near the treating centre for several weeks until engraftment is stable and it’s safe to go home

Do not use Waskyra if you have or have had:

• Hypersensitivity to the active substance or to any of the inactive ingredients.
• Previous treatment with hematopoietic stem cell transplant (HSCT) within 6 months before screening or HSCT with evidence of residual donor cells.
• Previous treatment with hematopoietic stem cell gene therapy.
• Contraindications to the mobilization and the conditioning regimen.

Common Waskyra side effects

The most common Waskyra side effects are bacterial and viral infections, diarrhea, vomiting, mouth ulcers or sores (stomatitis), liver injury, head injury, sneezing, runny or stuffy nose (rhinitis), cough, rash, tiny, flat, red/purple spots on the skin (petechiae), hypersensitivity, anemia, fever due to very low number of neutrophils, nosebleed, fever, catheter-related infections and complications.

Serious side effects, warnings, and precautions

Allergic and infusion reactions Some people can have serious allergic reactions or reactions during the infusion. Your healthcare team will watch you closely during and after the infusion.

Engraftment failure (treatment not “taking”) Very rarely, the modified stem cells may not grow properly in the bone marrow (called engraftment failure). If this happens, doctors may need to give you the back-up (unmodified) stem cells collected before treatment.

Low blood counts (cytopenias) After treatment, your red blood cells, white blood cells, or platelets can become very low for several weeks after reduced-intensity conditioning and Waskyra infusion. This can cause tiredness, infections, or bleeding and bruising. Your blood counts will be checked regularly for at least 8 weeks, and you’ll be treated if needed.

Serious infections Serious infections can occur, especially because of other medicines given with Waskyra (like rituximab) and the conditioning regimen. You’ll be monitored closely for fevers or other signs of infection before and after treatment and given antibiotics or other medicines if needed.

Infections possibly carried by the product It is possible, though very rare, that an infection could be passed on through the cell product itself. Any suspected infections related to Waskyra will be reported and investigated by the manufacturer and your healthcare team.

Liver blood vessel problem (veno-occlusive disease) A rare but serious liver condition called hepatic veno-occlusive disease can occur. Your liver tests and symptoms (such as weight gain, swelling, or pain in the upper right side of your abdomen) will be checked for at least one month after treatment.

Long-term risk of cancer Because Waskyra uses a lentiviral vector to insert a working copy of the gene, there is a small, lifelong risk of developing certain types of cancer (secondary malignancies). You will need to be monitored for any signs of cancer.

HIV test interference After receiving Waskyra, some HIV blood tests (PCR-based tests) may show a false positive, due to LVV provirus insertion. If you need a HIV test youshould not be tested using a PCR-based assay.

No donating blood or organs After treatment with Waskyra, you must not donate blood, organs, tissues, or cells for other people at any time in the future.

Pregnancy

Waskyra must not be administered during pregnancy due to the risk associated with conditioning treatment. Pregnancy after Waskyra infusion should be discussed with the treating physician. A negative serum pregnancy test must be confirmed before the start of mobilization and reconfirmed before conditioning

Contraception

Males capable of fathering a child and females of childbearing age should use an effective method of contraception from the start of mobilization through at least 6 months after administration of Aaskyra.

Infertility

There is no data yet on how Waskyra affects fertility. You should check the Prescribing Information for the medicines used in the conditioning regimen, as these may impact fertility.

Before conditioning treatment starts, the treating physician should discuss fertility preservation options with the patient or, in the case of children, with their parents or carers. This may include cryopreservation (freezing) of spermatogonial stem cells or ovarian tissue so that future fertility options are preserved as much as possible.

Breastfeeding

There are no data on the presence of Waskyra in human or animal milk, the effects on the breastfed child, or the effects on milk production. Because of the potential risks associated with conditioning, breastfeeding should be discontinued during conditioning. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Waskyra and any potential adverse effects on the breastfed child from WASKYRA or from the underlying maternal condition.

For single-dose intravenous use only.

Recommended Dose

• The minimum recommended dose of Waskyra is 7 × 106 CD34+ cells/kg based on patient’s body weight at the time of infusion.
• The maximum volume of Waskyra to be administered should remain less than 20% of the patient’s estimated plasma volume.

Vaccines

The safety and effectiveness of vaccination during or following Waskyra treatment have not been studied. It is unknown how safe or effective vaccines are during or after treatment with Waskyra.

Live Vaccines. Vaccination with live virus vaccines is not recommended until immune reconstitution is completed following treatment with Waskyra. Your specialist will tell you when it is safe to restart or catch up on vaccines.

HIV medicines (antiretrovirals)

Anti-retroviral medicines (HIV drugs) can interfere with the manufacturing of Waskyra. Because of this, patients must not take anti-retroviral medicines:

• For at least 1 month before mobilization, and
• Until at least 7 days after the Waskyra infusion.

If you are exposed to HIV or HTLV and need anti-retroviral treatment after that exposure, Waskyra treatment should be delayed. Doctors will wait until HIV/HTLV blood tests (western blot and viral load) are done 6 months after the exposure before starting Waskyra.

Always tell your healthcare team about all vaccines and HIV medicines you are taking or might need before, during, or after Waskyra treatment.

Store WASKYRA in the vapor phase of liquid nitrogen at less than -130°C (-202°F) until ready for thaw and administration.

Thaw Waskyra before infusion.

Thawing

• After carefully removing from the metal cassette, thaw the infusion bag in its sealed overwrap bag at 37°C (98.6°F) in a controlled thawing device until there is no visible ice in the infusion bag.
• Once thawing is complete, the bag should be removed immediately from the thawing device.
• The overwrap bag should be carefully opened to remove the infusion bag, which should be kept at room temperature (20°C – 25°C) until infusion. Gently massage the infusion bag to resuspend the cells. The content of the infusion bag should be inspected for any remaining visible cellular aggregates. Small clumps of cellular material should disperse with gentle manual mixing. Do not shake the bag.
• To maintain product viability, as soon as possible after thawing is complete, it is recommended that Waskyra be administered immediately.

Fondazione Telethon ETS Via Varese 16/B 00185 Rome Italy