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Elivaldogene Autotemcel

FDA Drug Information • Also known as: Skysona

Brand Names
Skysona
Route
INTRAVENOUS
Dosage Form
SUSPENSION
Product Type
CELLULAR THERAPY

⚠ Boxed Warning (Black Box)

WARNING: HEMATOLOGIC MALIGNANCY Hematologic malignancies, including life-threatening cases of myelodysplastic syndrome and acute myeloid leukemia, have occurred in patients treated with SKYSONA. Patients have been diagnosed between 14 months and 10 years after SKYSONA administration, and the cancers appear to be related to treatment with SKYSONA. Monitor patients closely for evidence of malignancy through complete blood counts at least every 3 months. Monitor patients through assessments for evidence for clonal expansion or predominance at least twice in the first year and annually thereafter; consider bone marrow evaluations as clinically indicated [see Warnings and Precautions (5.1) ] . WARNING: HEMATOLOGIC MALIGNANCY See full prescribing information for complete boxed warning. Hematologic malignancies, including life-threatening cases of myelodysplastic syndrome and acute myeloid leukemia, have occurred in patients treated with SKYSONA. The cancers appear to be the result of treatment with SKYSONA. Monitor patients closely for evidence of malignancy through complete blood counts at least every 3 months and through assessments for evidence for clonal expansion or predominance at least twice in the first year and annually thereafter; consider bone marrow evaluations as clinically indicated. ( 5.1 )

Description

11 DESCRIPTION SKYSONA (elivaldogene autotemcel) is an autologous HSC-based gene therapy prepared from the patient's HSCs, which are collected via apheresis procedure(s). The autologous cells are enriched for CD34+ cells, then transduced ex vivo with Lenti-D LVV, and cultured with growth factors overnight. Lenti-D LVV is a replication-incompetent, self-inactivating LVV carrying ABCD1 cDNA that encodes normal ALDP. The ABCD1 gene is under the control of an internal MNDU3 promoter, which is a modified viral promoter and has been shown to control expression of the transgene in HSCs and their progeny in all lineages. The transduced CD34+ cells are washed, formulated into a suspension, and then cryopreserved. SKYSONA is frozen in a patient-specific infusion bag(s) and is thawed prior to administration [see Dosage and Administration (2.1) , How Supplied/Storage and Handling (16) ]. The thawed product is colorless to white to red, including shades of white or pink, light yellow, and orange suspension of cells and may contain small proteinaceous particles. Due to the presence of cells, the solution may be clear to slightly cloudy and may contain visible cell aggregates. The formulation contains 5% dimethyl sulfoxide (DMSO).

What Is Elivaldogene Autotemcel Used For?

1 INDICATIONS AND USAGE SKYSONA is indicated to slow the progression of neurologic dysfunction in boys 4-17 years of age with early, active cerebral adrenoleukodystrophy (CALD) without an available human leukocyte antigen (HLA)-matched donor for allogeneic hematopoietic stem cell transplant. Early, active cerebral adrenoleukodystrophy refers to asymptomatic or mildly symptomatic (neurologic function score, NFS ≤ 1) boys who have gadolinium enhancement on brain magnetic resonance imaging (MRI) and Loes scores of 0.5-9. This indication is approved under accelerated approval based on 24-month Major Functional Disability (MFD)-free survival [see Clinical Studies (14) ] . Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). SKYSONA is an autologous hematopoietic stem cell-based gene therapy indicated to slow the progression of neurologic dysfunction in boys 4-17 years of age with early, active cerebral adrenoleukodystrophy (CALD) without an available human leukocyte antigen (HLA)-matched donor for allogeneic hematopoietic stem cell transplant. Early, active CALD refers to asymptomatic or mildly symptomatic (neurologic function score, NFS ≤ 1) boys who have gadolinium enhancement on brain magnetic resonance imaging (MRI) and Loes scores of 0.5-9. This indication is approved under accelerated approval based on 24-month Major Functional Disability (MFD)-free survival. [see Clinical Studies (14) ] . Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). ( 1 ) Limitations of Use SKYSONA does not treat or prevent adrenal insufficiency. ( 1 ) An immune response to SKYSONA may cause rapid loss of efficacy of SKYSONA in patients with full deletions of the human adenosine triphosphate binding cassette, sub family D, member 1 ( ABCD1) gene. ( 1 ) SKYSONA has not been studied in CALD secondary to head trauma. ( 1 ) Given the risk of hematologic malignancy with SKYSONA, and unclear long-term durability of SKYSONA and human adrenoleukodystrophy protein (ALDP) expression, careful consideration should be given to the timing of treatment for each boy and treatment of boys with isolated pyramidal tract disease as clinical manifestations do not usually occur until adulthood. ( 1 ) Limitations of Use SKYSONA does not prevent the development of or treat adrenal insufficiency due to adrenoleukodystrophy. An immune response to SKYSONA may limit the persistence of descendent cells of SKYSONA, causing rapid loss of efficacy of SKYSONA in patients with full deletions of the human adenosine triphosphate binding cassette, sub family D, member 1 ( ABCD1) gene. SKYSONA has not been studied in patients with CALD secondary to head trauma. Given the risk of hematologic malignancy with SKYSONA, and unclear long-term durability of SKYSONA and human adrenoleukodystrophy protein (ALDP) expression, careful consideration...

Dosage and Administration

2 DOSAGE AND ADMINISTRATION For autologous use only. For intravenous use only. For autologous use only. For intravenous use only. Patients must undergo hematopoietic stem cell (HSC) mobilization and apheresis to obtain CD34+ cells for SKYSONA manufacturing. ( 2.2 ) Dosing of SKYSONA is based on the number of CD34+ cells in the infusion bag(s) per kg of body weight. ( 2.1 ) The minimum recommended dose is 5.0 × 10 6 CD34+ cells/kg. ( 2.1 ) Full myeloablative and lymphodepleting conditioning must be administered before infusion of SKYSONA. ( 2.2 ) Verify the patient's identity matches the unique patient identification information on the SKYSONA infusion bag(s) prior to infusion. ( 2.2 ) Do not sample, alter, or irradiate SKYSONA. ( 2.2 ) Do not use an in-line blood filter or an infusion pump. ( 2.3 ) 2.1 Dose SKYSONA is provided as a single dose for infusion containing a suspension of CD34+ cells in one or two infusion bags. The minimum recommended dose of SKYSONA is 5.0 × 10 6 CD34+ cells/kg. The dose is calculated based on the patient's weight prior to first apheresis. See the Lot Information Sheet provided with the product shipment for additional information pertaining to dose. 2.2 Preparation Before SKYSONA Infusion Before mobilization, apheresis, and conditioning are initiated, confirm that hematopoietic stem cell (HSC) transplantation is appropriate for the patient. Perform screening for hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus 1 & 2 (HIV-1/HIV-2) and Human T-lymphotropic virus 1 & 2 (HTLV-1/HTLV-2) in accordance with clinical guidelines before collection of cells for manufacturing. Mobilization and Apheresis Patients are required to undergo HSC mobilization followed by apheresis to obtain CD34+ cells for product manufacturing. Weigh the patient prior to the first apheresis collection. Collect a minimum number of CD34+ cells of 12 × 10 6 CD34+ cells/kg. A back-up collection of CD34+ cells of ≥ 1.5 × 10 6 CD34+ cells/kg (if collected by apheresis) or ≥ 1.0 × 10 8 TNC/kg (Total Nucleated Cells, if collected by bone marrow harvest) is required. Collect and cryopreserve these cells prior to initiating conditioning and infusion with SKYSONA. The back-up collection may be needed for rescue treatment if there is: 1) compromise of SKYSONA after initiation of conditioning and before SKYSONA infusion, 2) primary engraftment failure, or 3) loss of engraftment after infusion with SKYSONA. Myeloablative and Lymphodepleting Conditioning Full myeloablative and lymphodepleting conditioning must be administered before infusion of SKYSONA. Consult prescribing information for the conditioning agents prior to treatment. Do not begin conditioning until SKYSONA has been received and stored at the treatment center and the availability of the back-up collection of CD34+ cells is confirmed. After completion of conditioning, allow a minimum of 48 hours of washout before SKYSONA infusion. Receipt and Storage of SKYSONA Ensure the...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS Most common non-laboratory adverse reactions (≥ 20%): mucositis, nausea, vomiting, febrile neutropenia, alopecia, decreased appetite, abdominal pain, constipation, pyrexia, diarrhea, headache, rash. ( 6.1 ) Most common Grade 3 or 4 laboratory abnormalities (≥ 40%): leukopenia, lymphopenia, thrombocytopenia, neutropenia, anemia, hypokalemia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact bluebird bio at 1-833-999-6378 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 reflect exposure to a single dose of SKYSONA in 67 patients with CALD. Data were obtained from two single-arm trials and, for 36 patients, from a long-term follow-up study [see Clinical Studies (14) ] . The median (min, max) age across studies was 6 (4, 14) years; 100% were male; 54% were White/Caucasian, 4% were Black or African American, 1% were Asian, 10% were of other races including mixed race, and 30% did not report race; 25% were of Hispanic ethnicity. The median (min, max) duration of follow-up at time of initial approval was 24 (1, 88) months. In the two trials, serious adverse reactions from Day 1 (SKYSONA infusion) to last follow-up occurred in 54% of patients. The most common non-laboratory, serious adverse reactions (≥ 3% incidence) that occurred after treatment with SKYSONA were febrile neutropenia (18%), pyrexia (fever) (18%), seizure (7%), myelodysplastic syndrome (4%), pseudomonal bacteremia (3%), pancytopenia (3%), vascular device infection (3%), mucositis (3%), and vomiting (3%). Most common non-laboratory adverse reactions by time of onset follow: During mobilization and conditioning and occurring in ≥ 20% of patients: nausea (79%), vomiting (72%), decreased appetite (42%), catheter site pain (39%), constipation (30%), headache (24%), abdominal pain (21%), rash (13%) In the first 60 days after treatment with SKYSONA in ≥ 15% of patients: mucositis (88%), febrile neutropenia (73%), alopecia (72%), abdominal pain (33%), vomiting (31%), decreased appetite (31%), pyrexia (27%), nausea (27%), constipation (21%), diarrhea (21%), epistaxis (19%), pruritus (18%), headache (16%), oropharyngeal pain (16%), skin hyperpigmentation (16%), anxiety (15%) Between 60 days and 1 year after treatment with SKYSONA in ≥ 5% of patients: pyrexia (fever) (9%) and vomiting (6%) Table 1 presents non-laboratory adverse reactions reported in at least 10% of patients between the start of conditioning and 24 months after SKYSONA administration. Table 2 presents Grade 3 or 4 laboratory abnormalities that occurred in at least 40% of patients between the start of conditioning and 24 months after SKYSONA administration. Table 1: Non-Laboratory Adverse Reactions Reported in ≥ 10% of Patients Between the Start of Conditioning and 24 Months Following Treatment with SKYSONA Includes adverse events associated with conditioning. Adverse Reaction Any Grade n (%) Grade 3 or Higher n (%) Blood and lymphatic system disorders -- -- Febrile neutropenia Febrile neutropenia includes febrile bone marrow aplasia and febrile neutropenia. 49 (73%) 49 (73%) Cardiac disorders -- -- Tachycardia Tachycardia includes sinus tachycardia and tachycardia. 10 (15%) 0 Eye disorders -- -- Vision blurred 7 (10%) 0 Gastrointestinal disorders -- -- Mucositis Mucositis includes anal inflammation, colitis, gastrointestinal inflammation, mucosal inflammation, proctitis, and stomatitis. Encompasses more than one system organ class. 62 (92%) 34 (51%) Nausea 56 (84%) 17 (25%) Vomiting 51 (76%) 12 (18%) Abdominal pain Abdominal pain includes abdominal discomfort, abdominal pain, and abdominal pain upper. 30 (45%) 2 (3%) Constipation 28 (42%) 0 Diarrhea 19...

Drug Interactions

7 DRUG INTERACTIONS Anti-retrovirals : Do not take these medications from at least one month prior to starting mobilization agents until all cycles of apheresis are complete and after the expected duration of elimination. ( 7.2 ) 7.1 Vaccines The safety and effectiveness of vaccination during or following SKYSONA treatment have not been studied. Vaccination is not recommended during the 6 weeks preceding the start of myeloablative conditioning, and until hematological recovery following treatment with SKYSONA. Where feasible, administer childhood vaccinations prior to myeloablative conditioning for SKYSONA. 7.2 Anti-retrovirals Patients should not take anti-retroviral medications for at least one month prior to initiating medications for stem cell mobilization and for the expected duration for elimination of the medications, and until all cycles of apheresis are completed [see Warnings and Precautions (5.5) ] . Anti-retroviral medications may interfere with SKYSONA manufacture.

Contraindications

4 CONTRAINDICATIONS None. None. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary There are no available data with SKYSONA administration in pregnant women. Consider the risks associated with mobilization and conditioning agents on pregnancy and fertility. No animal reproductive and developmental toxicity studies have been conducted to assess whether SKYSONA can cause fetal harm when administered to a pregnant woman. No nonclinical germline transmission studies have been conducted with SKYSONA. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING SKYSONA is supplied in one or two infusion bags containing a frozen suspension of genetically modified autologous cells enriched for CD34+ cells. Each bag contains approximately 20 mL. Each SKYSONA infusion bag is individually packed within an overwrap in a metal cassette. SKYSONA is shipped from the manufacturing facility to the infusion center in a cryoshipper, which may contain multiple metal cassettes intended for treatment of a single patient. A Lot Information Sheet is affixed inside the shipper. 20 mL infusion bag, overwrap, and metal cassette (NDC 73554-2111-1) Match the identity of the patient with the patient identifiers on the metal cassette(s), infusion bag(s), and Lot Information Sheet upon receipt. Store SKYSONA frozen in the vapor phase of liquid nitrogen at less than or equal to -140°C (-220°F) until ready for thaw and administration. Thaw SKYSONA prior to infusion [see Dosage and Administration (2) ]. Do not re-freeze after thawing. Do not irradiate SKYSONA as this could lead to inactivation.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.