A one-time gene therapy, managed through a highly coordinated and personalized process¹

Stem Cell Collection (~1 week)

• Patient undergoes hematopoietic stem cell mobilization (5–6 days) followed by apheresis (2–3 days) to obtain CD34+ stem cells for ZYNTEGLO manufacturing. Apheresis generally occurred on mobilization days 5 and 6

Additional information

• The treating physician should confirm HSC transplantation is appropriate for the patient and perform screening for HBV, HCV, HTLV, and HIV before mobilization and apheresis are initiated
• Patients should not take prophylactic HIV anti-retroviral medications or hydroxyurea for at least one month prior to mobilization or the expected duration for elimination of the medications, and until all cycles of apheresis are completed
• If a patient requires anti-retrovirals for HIV prophylaxis, mobilization and apheresis of CD34+ cells should be delayed until a negative test for HIV is confirmed
• Patients should be maintained at a hemoglobin (Hb) ≥11 g/dL for at least 30 days prior to mobilization
• If the minimum dose of 5.0 x 10⁶ CD34+ cells/kg is not met, mobilization and apheresis may be repeated to obtain collection of sufficient stem cells
• A back-up collection of CD34+ stem cells of ≥1.5 x 10⁶ CD34+ cells/kg (if collected by apheresis) or >1.0 x 10⁸ TNC/kg (if collected by bone marrow harvest) is required
• The back-up collection may be needed for rescue treatment if there is a compromise of hematopoietic stem cells or ZYNTEGLO before infusion, primary engraftment failure, or loss of engraftment after infusion with ZYNTEGLO

HBV = hepatitis B virus; HCV= hepatitis C virus; HIV = human immunodeficiency virus; HSC = hematopoietic stem cells; HTLV = human T-lymphotropic virus [HTLV-1, HTLV-2]; TNC = total nucleated cell count.

Manufacturing (~70-90 days)

• The patient’s cells are sent to a manufacturing site to produce ZYNTEGLO. ZYNTEGLO is then supplied in one or more infusion bags
• ZYNTEGLO is specifically manufactured for each individual patient by adding functional copies of a modified β-globin gene into the patient’s CD34+ stem cells
• ZYNTEGLO is then cryopreserved and, after passing quality release testing, stored until it is ready to be shipped to the QTC

Conditioning (4 days + at least 48 hours washout)

• Full myeloablative conditioning (chemotherapy given over 4 days) must be administered before infusion of ZYNTEGLO
• In clinical trials, all patients received full myeloablative conditioning with busulfan
• After completion of the conditioning, a minimum of 48 hours of washout should be allowed for before ZYNTEGLO infusion

Considerations

• Conditioning should not begin until the ZYNTEGLO has been received and stored at the treatment center and the availability of the back-up collection is confirmed
• Like mobilization, patients should be maintained at a Hb ≥11 g/dL for at least 30 days prior to myeloablative conditioning
• Iron chelation should be stopped at least 7 days prior to conditioning
• Prophylaxis for hepatic veno-occlusive disease (VOD) is recommended and should be considered for seizures