Atidarsagene Autotemcel

LENMELDY inserts one or more functional copies of the human ARSA complementary deoxyribonucleic acid (cDNA) into the patients’ HSCs, through transduction of autologous CD34 + cells with ARSA LVV. After LENMELDY infusion, transduced CD34 + HSCs engraft in bone marrow, repopulate the hematopoietic compartment and their progeny produce ARSA enzyme.

• 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).

• None.contraindicated

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.

Thrombosis and Thromboembolic Events : Evaluate the risk factors for thrombosis prior to and after LENMEDLY infusion. Consider prophylaxis with anti-thrombotic agents prior to treatment with LENMELDY. ( 5.1 ) Encephalitis : Monitor children for signs or symptoms of encephalitis after treatment with LENMELDY. ( 5.2 ) Serious Infection : Monitor children for serious infection after myeloablative conditioning and LENMELDY infusion. ( 5.3 ) Veno-occlusive Disease : Monitor children for signs and symptoms of VOD including liver function tests in all patients during the first month after LENMELDY infusion. Consider prophylaxis for VOD. ( 5.4 ) Delayed Platelet Engraftment : Monitor children for thrombocytopenia and bleeding until platelet recovery is achieved. ( 5.5 ) Risk of Neutrophil Engraftment Failure : Monitor absolute neutrophil counts (ANC) after LENMELDY infusion. If neutrophil engraftment does not occur, administer rescue cells. ( 5.6 ) Risk of Insertional Oncogenesis: Monitor children for hematologic malignancies annually after treatment with LENMELDY. ( 5.7 ) Risk of Hypersensitivity Reactions : Monitor for hypersensitivity reactions during infusion. ( 5.8 ) 5.1 Thrombosis and Thromboembolic Events Treatment with LENMELDY may increase the risk of thrombosis and thromboembolic events. A child with PSEJ MLD died after experiencing a left hemisphere cerebral infarction secondary to a thrombotic event in a large blood vessel approximately one year after treatment with LENMELDY.

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.

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. 8.2 Lactation Risk Summary There are no data on the presence of LENMELDY in human or animal milk, the effects on the breastfed child, or the effects on milk production. Because of the potential risks associated with myeloablative conditioning, breast-feeding should be discontinued during conditioning. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for LENMELDY and any potential adverse effects on the breastfed child from LENMELDY or from the underlying maternal condition. Breast-feeding after LENMELDY infusion should be discussed with the treating physician. Children receiving breast milk may continue to do so throughout their treatment under the advice of their treating physician.

Metabolism

LENMELDY is an autologous gene therapy which includes hematopoietic stem cells (HSCs) that have been genetically modified ex vivo. The nature of LENMELDY is such that conventional pharmacokinetic studies on absorption, distribution, metabolism, and excretion are not applicable.

1. 1Drug Ineffective229%
2. 2Encephalitis229%
3. 3B Precursor Type Acute Leukaemia114%
4. 4Cerebral Haemorrhage114%
5. 5Glioma114%
6. 6Immune Thrombocytopenia114%

The 1 most recently updated of 1 ClinicalTrials.gov registrations naming Atidarsagene Autotemcel as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• OTL-200 in Patients With Late Juvenile Metachromatic Leukodystrophy (MLD)
  Active not recruiting · Phase 3 · Interventional · 6 enrolled · Orchard Therapeutics
  NCT04283227updated 2025-09-05

Frequently asked questions

How does Atidarsagene Autotemcel work?

LENMELDY inserts one or more functional copies of the human ARSA complementary deoxyribonucleic acid (cDNA) into the patients’ HSCs, through transduction of autologous CD34 + cells with ARSA LVV. After LENMELDY infusion, transduced CD34 + HSCs engraft in bone marrow, repopulate the hematopoietic compartment and their progeny produce ARSA enzyme.

What is Atidarsagene Autotemcel used for?

According to FDA labeling, Atidarsagene Autotemcel carries indications including: 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).. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Atidarsagene Autotemcel?

Atidarsagene Autotemcel is classified as Enzymes, Gene Transduction or Replacement, Increased Hematopoiesis.

What are the brand names for Atidarsagene Autotemcel?

Atidarsagene Autotemcel is marketed under brand names including Lenmeldy.

What are the contraindications for Atidarsagene Autotemcel?

Atidarsagene Autotemcel labeling lists contraindications including: None.. Always consult the full prescribing information and a clinician.