STEP 1

Pre-treatment¹

While preparing for treatment, confirm that autologous hematopoietic stem cell (HSC) transplantation is appropriate for the patient before mobilization and apheresis and before myeloablative conditioning is initiated.

• Patients are prepared for mobilization with at least 2 cycles of scheduled transfusions (1 each month) with erythrocytapheresis being preferred
• For at least 60 days prior to mobilization and through myeloablative conditioning, patients should undergo a transfusion regimen to reach a target Hb of 8-10 g/dL, not to exceed 12 g/dL, and HbS of less than 30% to reduce the risk of SCD-related complications
• Perform screening for infectious diseases, specifically human immunodeficiency virus 1 & 2 (HIV-1/HIV-2), in accordance with clinical guidelines before collection of cells for manufacturing

STEP 2

Stem Cell Collection¹

• Patients will undergo 1 mobilization cycle followed by apheresis. More than 1 mobilization cycle may be required. For patients undergoing more than 1 mobilization cycle, separate each cycle by at least 14 days*
• Maximize CD34+ cell collection to obtain as many CD34+ stem cells as possible for product manufacturing during each mobilization and apheresis cycle. Target a minimum collection of 16.5 × 10⁶ CD34+ cells/kg for manufacturing and backup
• If, after manufacturing, the minimum dose of 3 × 10⁶ CD34+ cells/kg is not achieved, the patient may undergo additional cycles of mobilization and apheresis, separated by at least 14 days, to obtain more cells for additional manufacture. Multiple drug product lots may be administered to comprise the final dose
• A collection of CD34+ cells of ≥1.5 × 10⁶ CD34+ cells/kg is required for backup. These cells must be collected from the patient and be cryopreserved prior to myeloablative conditioning. The backup collection may be needed for rescue treatment

*There is a risk of sickle cell crisis during stem cell mobilization. Mobilization and apheresis triggered SAEs of sickle cell crisis in 6 (14%, 6/44) patients who initiated mobilization in the intent-to-treat population.

AN IMPORTANT NOTE ABOUT STEM CELL COLLECTION

Most people were treated with LYFGENIA using the minimum number of blood stem cells with 1 or 2 cycles of mobilization and apheresis, but additional cycles may be required

STEP 3

Production^1,2

The manufacturing of LYFGENIA consists of the selection and enrichment of CD34+ cells (hematopoietic stem cells) followed by the transduction of the enriched CD34+ cells with BB305 lentiviral vector.¹

• Collected cells are enriched for CD34+ cell population to have a greater proportion of CD34+ cells¹
• The majority of drug products will be manufactured, fully tested, and ready for release in 70 to 105 days, but in some cases can take up to 150 days²
• This step includes manufacturing, quality testing, releasing, and preparation for shipment of LYFGENIA²

STEP 4

Conditioning & Washout¹

Full myeloablative conditioning (4 days) is followed by a washout period of at least 48 hours prior to infusion of LYFGENIA.

• Do not begin myeloablative conditioning until the complete set of infusion bag(s) constituting the dose of LYFGENIA has been received and stored at the treatment center and the availability of the back-up collection is confirmed. After completion of the myeloablative conditioning, allow a minimum of 48 hours of washout before LYFGENIA infusion.
• Administer seizure prophylaxis with agents other than phenytoin at least 12 hours prior to initiating busulfan. Do not use phenytoin because of its induction of cytochrome P450 and resultant increased clearance of busulfan
• Consider prophylaxis for hepatic veno-occlusive disease (VOD)/hepatic sinusoidal obstruction syndrome with ursodeoxycholic acid or defibrotide

STEP 5

Infusion¹

Each infusion bag of LYFGENIA is administered via intravenous infusion over a period of less than 30 minutes per bag. LYFGENIA is supplied in 1 to 4 infusion bags. Confirm that patient identity matches the unique patient identifiers located on the LYFGENIA infusion bag(s).

• Coordinate the timing of LYFGENIA thaw and infusion. Confirm the infusion time in advance and adjust the start time of LYFGENIA thaw such that it will be available for infusion when the patient and healthcare providers are ready. Note that each infusion bag must be completely administered within 4 hours after thawing

STEP 6

Post-infusion Monitoring¹

Patients should be prepared to remain hospitalized and monitored for an additional 3-6 weeks after infusion.

Post-Treatment: Long-Term Follow-Up

(≥15 Years)

Patients treated with LYFGENIA may develop hematologic malignancies and should have lifelong monitoring. Monitor for hematologic malignancies with a complete blood count (with differential) at least every 6 months for at least 15 years after treatment with LYFGENIA, and integration site analysis at Months 6, 12, and as warranted