WASKYRA

WASKYRA is an FDA-registered drug product whose active ingredient is ETUVETIDIGENE AUTOTEMCEL. It is labelled by Orphan Therapies LLC taken by intravenous and marketed as a human prescription drug product. Identifiers on file: NDC 87668-0100, application BLA125846, label effective 20260723. It is one of 2 FDA drug label records sharing the active ingredient ETUVETIDIGENE AUTOTEMCEL. This page reproduces the FDA-approved label text so you can check what a product is, who makes it and how it is supplied before discussing it with a pharmacist or prescriber.

Across FDA labelling, products containing ETUVETIDIGENE AUTOTEMCEL are most often described in connection with: hematopoietic stem, treatment pediatric, patients aged, wiskott-aldrich syndrome, cell transplantation, hsct appropriate, suitable human, leukocyte antigen. Wording differs between labels, and the full indications section on this page takes precedence when it is present.

1 INDICATIONS AND USAGE WASKYRA ® is indicated for the treatment of pediatric patients aged 6 months and older and adults with Wiskott-Aldrich Syndrome (WAS) who have a mutation in the WAS gene and for whom hematopoietic stem cell transplantation (HSCT) is appropriate and no suitable human leukocyte antigen (HLA)-matched related stem cell donor is available. WASKYRA ® is an autologous hematopoietic stem cell-based gene therapy indicated for the treatment of pediatric patients aged 6 months and older and adults with Wiskott-Aldrich Syndrome (WAS) who have a mutation in the WAS gene for whom hematopoietic stem cell transplantation (HSCT) is appropriate and no suitable human leukocyte antigen (HLA)-matched related hematopoietic stem cell donor is available. ( 1 )

2 DOSAGE AND ADMINISTRATION For autologous use only. For single-dose intravenous use only. For autologous use only. For intravenous use only. Patients are required to undergo hematopoietic stem and progenitor cell (HSPC) mobilization followed by apheresis to obtain CD34 + cells for WASKYRA ® manufacturing. ( 2.2 ) Dosing of WASKYRA ® is based on the number of CD34 + cells in the infusion bag(s) per kg of body weight at the time of infusion. ( 2.1 ) The minimum recommended dose is 7 x 10 6 CD34 + cells per kg. Reduced-intensity conditioning is required before infusion of WASKYRA ® . ( 2.2 ) Prior to WASKYRA ® infusion, confirm that the patient’s identity matches the essential unique patient information on the infusion bag(s). ( 2.3 ) 2.1 Recommended Dose The minimum recommended dose of WASKYRA ® is 7 × 10 6 CD34 + cells/kg based on patient’s body weight at the time of infusion. The maximum volume of WASKYRA ® to be administered should remain < 20% of the patient’s estimated plasma volume. 2.2 Patient Preparation before WASKYRA ® Infusion Mobilization and apheresis Mobilize hematopoietic stem and progenitor cells (HSPC) using G-CSF with plerixafor according to established protocols. Perform apheresis to collect CD34+ cells required for WASKYRA ® manufacturing following the mobilization procedure. Collect and cryopreserve a back-up supply of CD34 + stem cells containing at least 3 x 10⁶ CD34 + cells/kg from the patient. Complete this collection before initiating reduced intensity conditioning and WASKYRA ® infusion. Store the back-up collection for potential rescue treatment in the following scenarios: WASKYRA ® compromise after reduced intensity conditioning initiation but before scheduled infusion, primary engraftment failure, or prolonged bone marrow aplasia following WASKYRA ® treatment. Pre-treatment and conditioning Administer rituximab (anti-CD20 monoclonal antibody) approximately 22 days before WASKYRA ® administration to deplete autoreactive B-cells and provide pre-emptive treatment for potential lymphoproliferative disorder due to Epstein Barr Virus infection which is a risk factor in WAS patients. Administer busulfan and fludarabine for reduced intensity conditioning before infusion of WASKYRA ® to promote engraftment of the genetically modified autologous CD34 + cells. Do not begin conditioning until the complete set of infusion bag(s) constituting the dose of WASKYRA ® has been received and stored at the administration site. Confirm availability of the back-up collection. Premedication Administer intravenous chlorpheniramine (0.2 mg/kg, max. dose 10 mg), or an equivalent 15-30 minutes before the infusion of WASKYRA ® to reduce the possibility of an allergic reaction to the infusion. 2.3 Administration Receipt WASKYRA ® is shipped in the vapor phase of liquid nitrogen (<-130°C; -202°F) from the manufacturing site to the qualified treatment center for the infusion. The Lot Information Sheet and the Chain of Custody documentation travels with the cryoshipper. Upon arrival check the temperature on the display of the cryoshipper, open it using the proper DPI, and confirm the patient code, batch number and number of bags against product label(s). Transfer WASKYRA ® from the vapor phase of liquid nitrogen at less than -130°C (-202°F) to the treatment center vapor phase of liquid nitrogen storage (<-130°C; -202°F) until ready for thaw and administration. In the event of issues, contact Fondazione Telethon ETS at: 1-888-212-6928. Preparation for infusion WASKYRA ® contains human blood cells that are genetically modified with a replication-incompetent, self-inactivating lentiviral vector (LVV). Follow universal precautions and local biosafety guidelines for handling and disposal of WASKYRA ® to avoid potential transmission of infectious diseases. Checking prior to thawing Do not remove the metal cassette from cryogenic storage or thaw WASKYRA ® until the patient is ready to be infused. Coordinate the timing of WASKYRA ® thaw and infusion. Confirm the infusion time in advance and adjust the start time for thaw so that the treatment is available for infusion when the patient is ready. Ensure the correct number of infusion bags are present. When more than one bag of WASKYRA ® is provided, thaw one bag of WASKYRA ® at a time. If more than one infusion bag is provided, thaw and administer each infusion bag completely before proceeding to thaw the next infusion bag. Open the metal cassette and inspect the overwrap bag and infusion bag for any breaches of integrity before thawing. If an infusion bag is compromised, follow the local guidelines for handling of waste of human-derived material and contact Marketing Authorization Holder immediately. Prior to thawing WASKYRA ® , it must be verified that the patient identity matches the unique patient information reported on the packaging labels and Lot Information Sheet (LIS). WASKYRA ® is solely for autologous use. Do not thaw or infuse WASKYRA ® if the information on the patient-specific label on the infusion bag does not match the intended patient. Confirm that the infusion bag is within the expiration date. 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; 68°F – 77°F) 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 ® is administered immediately. Note: Do not sample, alter, irradiate or refreeze WASKYRA ® . Administration Prior to WASKYRA ® infusion, confirm that the patient’s identity matches the essential unique patient information on the infusion bag(s) labels. Administer WASKYRA ® as an intravenous infusion using a central venous catheter, per the qualified treatment site’s standard procedures for cell therapy products. When more than one bag of WASKYRA is needed, prior to infusion ensure that the volume of WASKYRA ® to be infused is compatible with the recommended limit of dimethyl sulfoxide (DMSO), i.e., the total volume of DMSO administered should remain < 1% of the patient’s estimated plasma volume. The maximum volume of WASKYRA ® to be administered should therefore remain < 20% of the patient’s estimated plasma volume. Ensure that the administration set consists of a blood transfusion set equipped with a 200 µm filter. Infuse each bag within 2 hours of thaw, including any interruption during the infusion, to maintain maximum product viability. Infuse contents of each bag within 30 minutes with a maximum infusion rate of 5 mL/kg/h. At the end of the infusion, flush all WASKYRA ® remaining in the infusion bag and any associated tubing with sodium chloride 9 mg/mL (0.9%) solution for injection to ensure that as many cells as possible are infused into the patient. Consider the infusion volume in relation to the age and weight of the patient. Monitor vital signs (blood pressure, heart rate, and oxygen saturation) and the occurrence of any symptom prior to the start of the infusion, approximately every ten minutes during the infusion and every hour, for 3 hours, after the infusion.

4 CONTRAINDICATIONS Hypersensitivity to the active substance or to any of the excipients [see Hypersensitivity and Infusion Related Reactions (5.1) ]. Previous treatment with HSCT within 6 months prior to treatment or HSCT with evidence of residual donor cells. Previous treatment with hematopoietic stem cell gene therapy. Contraindications to the mobilization and the conditioning regimen. Hypersensitivity to the active substance or to any of the excipients. ( 4 ) Previous treatment with HSCT within 6 months prior to screening or HSCT with evidence of residual donor cell. ( 4 ) Previous treatment with hematopoietic stem cell gene therapy. ( 4 ) Contraindications to the mobilization and the conditioning regimen. ( 4 )

6 ADVERSE REACTIONS The most common adverse reactions (incidence ≥ 20%) are catheter related infections, bacterial and viral infections, diarrhea, vomiting, stomatitis, liver injury, head injury, rhinitis, cough, rash, petechiae, hypersensitivity, anemia, febrile neutropenia, epistaxis, pyrexia, catheter site complications. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Fondazione Telethon ETS at toll-free phone 1-888-212-6928 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety data described in this section reflects exposure to WASKYRA ® in two clinical studies, Study 1 (201228) and Study 2 (OTL-103-4) as well as patients in expanded access program (EAP). A total of 27 patients received a single infusion of WASKYRA ® at a dose range of 7 to 31×10 6 CD34 + cells/kg (median dose: 16.90×10 6 CD34 + cells/kg). The median duration of the follow up was 5.67 years (range: 0.37-13.26 years) [see Clinical Studies (14) ]. During the above-mentioned clinical trials no adverse reactions attributable to the gene therapy were reported. There were 45 serious adverse reactions reported in 21 patients including catheter-related infections (n=11), bacterial and viral infections (n=10), pyrexia (n=3), prolonged neutropenia (n=2), vomiting (n=2), veno-occlusive disease (n=1), aspergillus infection (n=1). One patient died approximately 4.5 months after WASKYRA ® infusion due to neurological decompensation. Table 1: Adverse Reactions Occurring in ≥10% of Patients (N=27) Adverse Reactions Any Grade n (%) Grade 3 or higher n (%) Infections and Infestations - - Catheter related infection 16 (59) 14 (52) Respiratory tract infection Is a composite that includes multiple related terms. 18 (67) 4 (15) Conjunctivitis * 10 (37) 0 Cytomegalovirus infection * 8 (30) 4 (15) Epstein-Barr virus infection 5 (19) 1 (4) Gastroenteritis 5 (19) 2 (7) Ear infection 4 (15) 0 Oral candidiasis 4 (15) 0 Urinary tract infection * 5 (19) 3 (11) Balanoposthitis 3(11) 0 Gastrointestinal disorders - - Diarrhea * 16 (59) 3 (11) Vomiting 12 (44) 5 (19) Liver injury * 16 (59) 3 (11) Stomatitis 6 (22) 3 (11) Hematochezia 5 (19) 0 Abdominal pain 3 (11) 0 Constipation 3 (11) 0 Nervous System disorders - - Head Injury* 10 (37) 1 (4) Headache 4 (15) 2 (7) Respiratory, thoracic and mediastinal disorders - - Rhinitis 9 (33) 0 Cough * 8 (30) 0 Wheezing 4 (15) 0 Oropharyngeal pain 3 (11) 1 (4) Skin and subcutaneous tissue disorders - - Rash Rash includes eczema, rash, urticaria, dermatitis, dry skin, erythema. 23 (85) 9 (33) Petechiae 16 (59) 1 (4) Immune system disorders - - Hypersensitivity * 6 (22) 4 (15) Lymphadenopathy 4 (15) 1 (4) Blood and lymphatic system disorders - - Anemia * 11 (41) 4 (15) Immune thrombocytopenia 4 (15) 4 (15) Febrile neutropenia 7 (26) 6 (22) Epistaxis 9 (33) 0 Mouth hemorrhage 3 (11) 0 Traumatic hematoma * 4 (15) 0 General disorders and administration site conditions - - Pyrexia 11 (41) 6 (22) Catheter site complications Catheter site complications includes Catheter site inflammation, Catheter site hemorrhage, Unintentional medical device removal. 10 (37) 1 (4) Note: Adverse reactions are defined as adverse events occurred during conditioning and year 1 following WASKYRA ® administration. Other clinically significant adverse reactions that occurred in < 20% patients include papillary thyroid cancer diagnosed in one patient with a familial history of Graves' disease at 5-years post treatment. The tumor cells did not contain viral vector gene sequences. Table 2. Laboratory Abnormalities that Worsened from Baseline in ≥ 10% of Patients (N=27) Laboratory Abnormality All Grade n (%) Grade 3 or 4 n (%) Neutrophils decreased 10 (37) 9 (33) Eosinophils increased 7 (26) 1 (4) Electrolyte imbalance Electrolyte imbalance includes hypokalemia, hyperkalemia, hyponatremia, hypomagnesemia 11 (41) 6 (22) Creatinine increased 3 (11) 0 Calcium decreased 3 (11) 0

FDA lists 2 drug label records with ETUVETIDIGENE AUTOTEMCEL as the active ingredient. The most common dosage forms and the manufacturers with the most records are summarised below; strengths, pack sizes and inactive ingredients can still differ between apparently similar products.

What is WASKYRA used for?
1 INDICATIONS AND USAGE WASKYRA ® is indicated for the treatment of pediatric patients aged 6 months and older and adults with Wiskott-Aldrich Syndrome (WAS) who have a mutation in the WAS gene and for whom hematopoietic stem cell transplantation (HSCT) is appropriate and no suitable human leukocyte antigen (HLA)-matched related stem cell donor is available. WASKYRA ® is an autologous …

Who makes WASKYRA?
Orphan Therapies LLC is the labeler of record for WASKYRA. 2 FDA label records share the active ingredient ETUVETIDIGENE AUTOTEMCEL, so generic and branded versions may come from different companies; the manufacturer named on your pack is the one that matters for any enquiry.

What form does WASKYRA come in?
administered by intravenous. Strengths and pack sizes vary by label, so compare the NDC on your pack with the identifier listed on this page.

Is WASKYRA prescription or over-the-counter?
The FDA label for this product is recorded as human prescription drug. Marketing status can differ between strengths and countries, so check the dispensing rules where you live.

Are there other products containing ETUVETIDIGENE AUTOTEMCEL?
Yes. 2 FDA drug label records list ETUVETIDIGENE AUTOTEMCEL as the active ingredient. Products with the same active ingredient can usually be substituted only when a prescriber or pharmacist confirms it is appropriate.

Has WASKYRA been recalled?
No FDA recall record in our database matches this product name or manufacturer. Recall data is updated periodically, so a very recent notice may not appear here yet.

Where does this information come from?
All content is reproduced from FDA Structured Product Labelling data via openFDA. It is provided for identification and reference only and is not medical advice.