Atidarsagene Autotemcel
FDA Drug Information • Also known as: Lenmeldy
- Brand Names
- Lenmeldy
- Route
- INTRAVENOUS
- Dosage Form
- SUSPENSION
- Product Type
- CELLULAR THERAPY
Description
11 DESCRIPTION LENMELDY (atidarsagene autotemcel) is a gene therapy consisting of autologous CD34 + cells, containing hematopoietic stem cells (HSCs), transduced with a lentiviral vector (LVV) encoding the human arylsulfatase A (ARSA) gene, suspended in cryopreservation solution. LENMELDY is intended for one-time administration to add functional copies of the ARSA gene into the child’s own HSCs. LENMELDY is prepared from the child’s own HSCs, which are collected via apheresis procedure(s). The autologous cells are enriched for CD34 + cells, then transduced ex vivo with a recombinant replication-incompetent self-inactivating (SIN) human immunodeficiency virus-1 (HIV-1) - based LVV that has been modified to carry the ARSA cDNA sequence under the human phosphoglycerate kinase (PGK) promoter. The transduced CD34 + cells are washed, formulated into a suspension, and then cryopreserved. LENMELDY is manufactured for each individual child into infusion bags, which are cryopreserved before being thawed prior to administration [ see Dosage and Administration (2.2) , How Supplied/Storage and Handling (16) ]. The thawed product is a colorless to slightly yellow or pink cell suspension and may contain visible cell aggregates. The formulation contains 5% (v/v) dimethyl sulfoxide (DMSO). Each 1 mL of LENMELDY suspension for IV infusion contains 3.5 mg of sodium.
What Is Atidarsagene Autotemcel Used For?
1 INDICATIONS AND USAGE LENMELDY is indicated for the treatment of children with pre-symptomatic late infantile (PSLI), pre-symptomatic early juvenile (PSEJ) or early symptomatic early juvenile (ESEJ) metachromatic leukodystrophy (MLD). LENMELDY is an autologous hematopoietic stem cell-based gene therapyindicated for the treatment of children with pre-symptomatic late infantile (PSLI), pre-symptomatic early juvenile (PSEJ) or early symptomatic early juvenile (ESEJ) metachromatic leukodystrophy (MLD).
Dosage and Administration
2 DOSAGE AND ADMINISTRATION For autologous use only. For one-time single-dose intravenous use only. For autologous use only. For one-time single-dose intravenous use only. Children are required to undergo hematopoietic stem cell (HSC) mobilization followed by apheresis to obtain CD34+ cells for LENMELDY manufacturing. ( 2.2 ) Dosing of LENMELDY 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 based on the MLD disease subtype. ( 2.1 ) Myeloablative conditioning must be administered before infusion of LENMELDY. ( 2.2 ) Confirm that the child’s identity matches the unique patient identification information on the LENMELDY infusion bag(s) prior to infusion. ( 2.2 ) Do not sample, alter, irradiate, or refreeze LENMELDY. ( 2.2 ) Do not use a leukodepleting filter. ( 2.3 ) 2.1 Dose LENMELDY is provided as a single dose for infusion containing a suspension of CD34 + cells in one to eight infusion bags. Table 1 provides the minimum and maximum recommended dose of LENMELDY based on MLD disease subtype: Table 1: Minimum and Maximum Recommended Dose of LENMELDY MLD Subtype Minimum Recommended Dose (CD34 + cells/kg) Maximum Recommended Dose (CD34 + cells/kg) Pre-symptomatic late infantile 4.2 x 10 6 30 x 10 6 Pre-symptomatic early juvenile 9 x 10 6 30 x 10 6 Early symptomatic early juvenile 6.6 x 10 6 30 x 10 6 The dose administered is calculated based on the child’s weight at time of LENMELDY infusion using the information provided on the Lot Information Sheet. See the Lot Information Sheet provided with the product shipment for additional information pertaining to dose. 2.2 Preparation before LENMELDY Infusion Mobilization, apheresis, and myeloablative conditioning are required prior to LENMELDY infusion. Before initiating these procedures, confirm that hematopoietic stem cell (HSC) gene therapy is appropriate for the child. Screen children for hepatitis B virus (HBV), hepatitis C virus (HCV), human T-lymphotrophic virus 1 & 2 (HTLV-1/HTLV-2), human immunodeficiency virus 1 & 2 (HIV-1/HIV-2), cytomegalovirus (CMV), and mycoplasma infection in accordance with clinical guidelines before collection of cells for manufacturing. Mobilization and Apheresis Children are required to undergo HSC mobilization followed by apheresis to obtain CD34 + cells for LENMELDY manufacturing. In clinical trials of LENMELDY, granulocyte-colony stimulating factor (G-CSF) with or without plerixafor was used for mobilization. For the manufacture of LENMELDY, a collection of a minimum of 8.0 × 10 6 CD34 + cells/kg of autologous cells is required based on a weight at time of apheresis collection. Collection of the minimum number of CD34 + cells required for manufacture may be achieved using one or more cycles of mobilization. A collection of unmanipulated back-up CD34 + cells of at least 2.0 × 10 6 CD34 + cells/kg is required. These cells must be collected from the child and be cryopreserved prior to...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The most common non-laboratory adverse reactions (occurring in ≥10% of all children within Year 1 of treatment) were: febrile neutropenia (85%), stomatitis (77%), respiratory tract infections (54%), rash (33%), device related infections (31%), other viral infections (28%), pyrexia (21%), gastroenteritis (21%), and hepatomegaly (18%). The following clinically significant adverse reactions are described elsewhere in the labeling: Thrombosis and Thrombotic Events [ see Warnings and Precautions (5.1) ] Encephalitis [ see Warnings and Precautions (5.2) ] Serious Infection [ see Warnings and Precautions (5.3) ] Veno-occlusive Disease [ see Warnings and Precautions (5.4) ] Delayed Platelet Engraftment [ see Warnings and Precautions (5.5) ] Neutrophil Engraftment Failure [ see Warnings and Precautions (5.6) ] Insertional Oncogenesis [ see Warnings and Precautions (5.7) ] Hypersensitivity Reactions [ see Warnings and Precautions (5.8) ] The most common non-laboratory adverse reactions (incidence ≥ 10%) were: febrile neutropenia (85%), stomatitis (77%), respiratory tract infections (54%), rash (33%), device related infections (31%), other viral infections (28%), pyrexia (21%), gastroenteritis (21%), and hepatomegaly (18%). ( 6.1 ) The most common laboratory abnormalities were: elevated D-dimer (67%), neutropenia (28%), and elevated liver enzymes (23%). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Orchard Therapeutics at toll-free phone 1-888-878-0185 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 reflect experience from 39 children with MLD treated in clinical trials of LENMELDY: PSLI (n=20), PSEJ (n=7), ESEJ (n=10), and 2 children with advanced disease at the time of treatment [ see Clinical Studies (14) ]. The median (min, max) years of follow-up for the safety population was 6.8 (0.6, 12.2). Table 2 presents the non-laboratory treatment emergent adverse reactions occurring in ≥10% of all children with onset reported on or after the date of conditioning up to 1 year follow-up post-treatment. Table 2: Summary of Non-Laboratory Treatment Emergent Adverse Reactions Reported in at Least 10% of Patients Within Year 1 Following Treatment with LENMELDY (N = 39) Includes adverse events potentially related to busulfan myeloablative conditioning. Adverse reaction System Organ Class/Preferred Term Any Grade n (%) patients Grade 3 or higher n (%) patents Blood and lymphatic system disorders -- -- Febrile neutropenia 33 (85) 32 (82) Gastrointestinal disorders -- -- Stomatitis 30 (77) 29 (74) General disorders and administration site conditions -- -- Pyrexia 8 (21) 1 (3) Hepatobiliary disorders -- -- Hepatomegaly 7 (18) 0 Infections and infestations -- -- Respiratory tract infections Includes events with PTs of Bronchitis, Nasopharyngitis, Pharyngitis, Pneumonia, Respiratory tract infection, Rhinitis, Tonsillitis, Upper respiratory fungal infection and Upper respiratory tract infection. 21 (54) 3 (8) Device related infection Includes events of Bacterial sepsis, Catheter site cellulitis, Catheter site infection, Device related infection, Sepsis, and Vascular device infection. 12 (31) 7 (18) Gastroenteritis Includes events with PTs of Enteritis, Gastroenteritis, Gastroenteritis Aeromonas and Gastroenteritis rotavirus. 8 (21) 3 (8) Other viral infections Includes events with PTs of Adenovirus infection, Cytomegalovirus infection, Cytomegalovirus test positive, Cytomegalovirus viremia, Enterovirus infection, Hand-foot-and-mouth disease, Herpes zoster, SARSCov-2-test positive, and Viral infection (excluding PT of Gastroenteritis rotavirus). 11 (28) 2 (5) Skin and subcutaneous tissue disorders -- -- Rash Includes...
Drug Interactions
7 DRUG INTERACTIONS No formal drug interaction studies have been performed. LENMELDY is not expected to interact with the hepatic cytochrome P-450 family of enzymes or drug transporters. Anti-retrovirals : Do not take anti-retroviral medications for at least one month prior to initiating medications for stem cell mobilization and for the expected duration of time needed for the elimination of the medications. ( 7.2 ) 7.1 Vaccines The safety and effectiveness of vaccination during or following LENMELDY 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 LENMELDY. Where feasible, administer childhood vaccinations prior to myeloablative conditioning for LENMELDY. 7.2 Anti-retrovirals Children should not take anti-retroviral medications for at least one month prior to mobilization or the expected duration for elimination of the medications [ see Warnings and Precautions (5.5) ]. Anti-retroviral medications may interfere with the manufacturing of LENMELDY.
Contraindications
4 CONTRAINDICATIONS None. None ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary There are no clinical data from the use of LENMELDY in pregnant women. No animal reproductive and developmental toxicity studies have been conducted with LENMELDY to assess whether it can cause fetal harm when administered to a pregnant woman. LENMELDY must not be administered during pregnancy because of the risk associated with myeloablative conditioning. Pregnancy after LENMELDY infusion should be discussed with the treating physician. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING LENMELDY is supplied in up to eight infusion bags containing a frozen suspension of genetically modified autologous cells enriched for CD34 + cells. Each bag contains 10 to 20 mL of suspension. Each infusion bag is individually packed within an overwrap in a metal cassette. LENMELDY is shipped from the manufacturing facility to the treatment center storage facility in one to two cryoshipper(s), which may contain multiple metal cassettes intended for a single child. Two shippers would be used in the event that 5-8 bags are manufactured. A Lot Information Sheet is affixed inside the shipper. 50 mL infusion bag, overwrap, and metal cassette (NDC 83222-0200-1). Match the identity of the child with the patient identifiers on the metal cassette(s), infusion bag(s), and Lot Information Sheet upon receipt. Store LENMELDY in the vapor phase of liquid nitrogen at less than -130°C (-202°F) until ready for thaw and administration. Thaw LENMELDY prior to infusion [ see Dosage and Administration (2) ]. Do not re-freeze after thawing. Do not irradiate LENMELDY, 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.