You guide the care. We guide the process.
Overview of treatment with LYFGENIA™
LYFGENIA is a one-time treatment process that is administered at a Qualified Treatment Center (QTC). The main steps are1:
- Pre-treatment
- Stem cell collection
- LYFGENIA production
- Conditioning and washout
- LYFGENIA infusion
- Monitoring and follow-up
Referring to Qualified Treatment Centers
QTCs are independently owned and operated specialized hospitals. Each QTC has been carefully selected and trained to administer LYFGENIA, and the broad network of QTCs provides patients with convenient coast-to-coast access within the US.
The primary hematologist plays a pivotal role in identifying and referring appropriate patients for LYFGENIA. Through a shared-care approach, QTCs provide the specialized expertise, infrastructure, and treatment coordination required for gene therapy while keeping referring providers connected to key patient care decisions throughout the treatment journey.
Find a Qualified Treatment Center6 important steps to treatment with LYFGENIA
STEP 1
Pre-treatment
(Timing will vary by person)
Before recommending a patient receive LYFGENIA, confirm that autologous hematopoietic stem cell transplantation is appropriate for the patient.1
STEP 2
Stem Cell Collection
(~1+ weeks at the QTC)
Patients will undergo HSC mobilization followed by apheresis. More than one collection cycle may be required.1
STEP 3
LYFGENIA Production
(~10-15 weeks)
Once CD34+ stem cells are collected, they are sent to a central site for the manufacturing, quality testing, releasing, and preparation for shipment of LYFGENIA.1
STEP 4
Conditioning & Washout
(4 days + >2 days of recovery)
Prior to LYFGENIA infusion, patients will undergo full myeloablative conditioning followed by a 2-day minimum washout period.1
STEP 5
LYFGENIA Infusion
(~30 minutes per bag at QTC)
Once conditioning is complete it’s time for patient infusion. LYFGENIA is supplied in 1 to 4 infusion bags.1
STEP 6
Monitoring & Follow-up
(~3-6 weeks at QTC; ≥15 years long-term follow-up)
Once infusion is complete patients must be monitored in the hospital.1
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
Concomitant medications1
Manage other concomitant medications (as applicable) as described below:
- Hydroxyurea: Discontinue at least 2 months prior to mobilization. Patients should not resume hydroxyurea until all cycles of apheresis are completed
- Disease-modifying agents (eg, L-glutamine, voxelotor, and crizanlizumab): Discontinue at least 2 months prior to mobilization as the interaction between disease-modifying agents and mobilization agents is unknown
- Erythropoietin: Discontinue at least 2 months prior to mobilization
- Iron chelation: Discontinue at least 7 days prior to mobilization
- Granulocyte-colony stimulating factor (G-CSF): Do not administer G-CSF prior to or with mobilization agents
- Anti-retrovirals: Discontinue prophylactic HIV anti-retroviral medications at least 1 month prior to mobilization and do not resume until all cycles of apheresis are completed. There are some long-acting anti-retroviral medications that may require a longer duration of discontinuation for elimination of the medication
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.
Concomitant medications1
Manage other concomitant medications (as applicable) as described below:
- Transfusions: Scheduled transfusions can be continued between apheresis and conditioning. Patients should maintain total hemoglobin (Hb) levels of 8 to 10 g/dL. Hb levels should not exceed 12 g/dL. A scheduled transfusion should be performed within 2 days prior to conditioning
- Hydroxyurea: If administered after apheresis, discontinue hydroxyurea at least 2 days prior to myeloablative conditioning
- Disease-modifying agents (eg, L-glutamine, voxelotor, and crizanlizumab): Discontinue disease-modifying agents at least 2 months prior to conditioning, as the interaction between disease-modifying agents and conditioning agents is unknown
- Iron chelation: If administered after apheresis, discontinue iron chelation at least 7 days prior to myeloablative conditioning
- Granulocyte-colony stimulating factor (G-CSF): Do not administer G-CSF between mobilization and conditioning
- Anti-retrovirals and erythropoietin: There are no data regarding use of anti-retrovirals or erythropoietin between apheresis and conditioning
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
LYFGENIA Production1,2
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
Continuous refinement
Delivery in as little as 80 days from cell collection
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
LYFGENIA 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
Monitoring & Follow-up1
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
Concomitant medications1
Standard procedures for patient management after HSC transplantation should be followed after LYFGENIA infusion:
- Irradiate any blood products required for at least the first 3 months after LYFGENIA infusion and per transplant physician’s recommendation
- There is no experience regarding the use of hydroxyurea, anti-retrovirals, erythropoietin, or disease-modifying agents, such as voxelotor or crizanlizumab, after LYFGENIA infusion
- G-CSF is not recommended for 21 days after LYFGENIA infusion
- Patients should not donate blood, organs, tissues, or cells at any time in the future
- After infusion, avoid use of myelosuppressive iron chelators for 6 months. If iron chelation is needed, consider administration of non-myelosuppressive iron chelators. Phlebotomy can be used in lieu of iron chelation when appropriate
REMINDER
Preparation matters before, during, and after treatment
Preparation matters before, during, and after treatment
Knowing what to expect helps patients move forward with confidence, so it's important to set realistic expectations around treatment and recovery.
The LYFGENIA journey does not end at infusion
Patients treated with LYFGENIA require ongoing monitoring and long-term follow-up after infusion. Set expectations early that long-term monitoring remains an important part of care.
Advise patients on the following:
- The risk of manufacturing failure—in case of manufacturing failure or the need for additional cells, additional cell collection and manufacturing of LYFGENIA would be needed
- The risks associated with mobilization and myeloablative conditioning agents
Additionally advise patients of the following:
- Hematologic malignancy has occurred in patients treated with LYFGENIA. Patients with sickle cell disease have an increased risk of hematologic malignancy, compared to the general population. The additional hematopoietic stress associated with mobilization, conditioning, and infusion of LYFGENIA, including the need to regenerate the hematopoietic system, may increase the risk of a hematologic malignancy
- Delayed platelet engraftment has been observed with LYFGENIA. Patients should be made aware of the risk of bleeding until platelet recovery has been achieved
- Risk of neutrophil engraftment failure—patients who experience neutrophil engraftment failure will receive rescue treatment with their back-up collection of CD34+ cells
- Insertional oncogenesis—there is a potential risk of insertional oncogenesis after treatment with LYFGENIA. Patients should be monitored lifelong
- Monitoring will include assessment for hematologic malignancies with a complete blood count at least every 6 months for at least 15 years after treatment with LYFGENIA. This will include integration site analysis at Months 6, 12, and as warranted
Post-marketing long-term follow-up study:
Patients who intend to receive treatment with LYFGENIA are encouraged to enroll in the study, as available, to assess the long-term safety of LYFGENIA and the risk of malignancies occurring after treatment with LYFGENIA by calling Genetix Biotherapeutics at 1-833-999-6378. The study includes monitoring (at pre-specified intervals) for clonal expansion
Advise patients to:
- Have their treating physician contact Genetix Biotherapeutics at 1-833-999-6378 if patients are diagnosed with a malignancy
- Monitor for signs and symptoms of bleeding and have frequent blood draws for platelet counts until platelet recovery has been achieved
- Not donate blood, organs, tissues, or cells at any time in the future
- Understand that they may have a false-positive result for HIV if tested using a PCR-based assay after being treated with LYFGENIA