LENMELDY atidarsagene autotemcel 11800000 1/1 Suspension, 1 suspension
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This medicine belongs to the Enzymes class.
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UNII ZIF514RVZR
A protein derived from human blood plasma. In medicines, it acts as a stabilizer and binder, helping maintain drug potency and form, and may improve how the medication disperses or dissolves in the body.
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UNII YOW8V9698H
Dimethyl sulfoxide is a clear liquid solvent derived from wood pulp. In medicines, it helps dissolve or carry active ingredients and improve how the body absorbs the drug.
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UNII VR5Y7PDT5W
A saltwater solution with the same concentration as blood. It's used as a vehicle or diluent in injectable medicines to help distribute the active drug and maintain proper fluid balance in the body.
3 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
| Medicare Part B allowsASP · J3391 | No ASP payment limit on file for J3391 this quarter. | |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Lenmeldy 11800000 1this 83222-0200-01 | Orchard | 1 suspension | — | — | FDA listed | — |
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⏳ Availability & biosimilar status
Biologics have no small-molecule generics; biosimilar competition is tracked in the FDA Purple Book.
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- Biologic patent
- A patent the reference product’s maker has publicly listed. A biosimilar generally can’t launch until these expire — unless they’re invalidated or resolved in a settlement.
- Reference-product exclusivity
- A flat 12 years of FDA market protection from the biologic’s first licensure (the BPCIA). No biosimilar can be licensed before it ends, regardless of patents.
- Interchangeable exclusivity
- The first interchangeable biosimilar can earn a period as the only interchangeable version (pharmacists can substitute it without the prescriber).
- Earliest biosimilar (LOE)
- The latest of all the dates above — the soonest a biosimilar can realistically reach the market. Litigation and settlements can move it earlier.
Biologics have no small-molecule “generics” — competition comes from FDA-licensed biosimilars, tracked in the FDA Purple Book.
| Code | What it grants | Expires |
|---|---|---|
| RefProduct | Reference-product exclusivity (12-year, BPCIA) — no biosimilar can be licensed before this date | Mar 18, 2036 |
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 83222-0200-01 You're viewing this | 1 SUSPENSION in 1 BAG (83222-0200-1) | 2024-04-26 | Active |
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| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | — Not published for this NDC No photo available yet for this listing. |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | ✓ Available |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
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📄 Full FDA label FDA SPL
🎯 Indications and Usage ▾
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 )
2.1Dose 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.
2.2Preparation 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 myeloablative conditioning.
The back-up collection may be needed for rescue treatment if there is: 1) compromise of LENMELDY after initiation of conditioning but before infusion, 2) primary engraftment failure, or 3) loss of engraftment after infusion with LENMELDY. The back-up cells may be collected either through mobilized peripheral blood (mPB) apheresis or bone marrow collection. Myeloablative Conditioning Myeloablative conditioning must be administered before infusion of LENMELDY.
In clinical trials of LENMELDY, busulfan was used for myeloablative conditioning. There is no data available supporting the use of alternative conditioning agents with LENMELDY. Do not begin myeloablative conditioning until LENMELDY has been received and stored at the treatment center and the availability of the back-up collection of CD34 + cells has also been confirmed.
After completion of the myeloablative conditioning, allow a minimum of 24 hours of washout before LENMELDY infusion. Receipt and Storage of LENMEL…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS LENMELDY is a single-dose cell suspension for intravenous infusion. LENMELDY is composed of one to eight infusion bags which contain 2 to 11.8 × 10 6 cells/mL (1.8 to 11.8 x 10 6 CD34 + cells/mL) suspended in cryopreservation solution [ see How Supplied/Storage and Handling (16) ]. Each infusion bag contains 10 to 20 mL of LENMELDY.
See the Lot Information Sheet for actual dose. LENMELDY is a single-dose cell suspension for intravenous infusion. ( 3 ) LENMELDY is composed of one to eight infusion bags which contain 2 to 11.8× 10 6 cells/mL (1.8 to 11.8 x 10 6 CD34 + cells/ml) suspended in cryopreservation solution.
( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS None. None ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS 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 )
5.1Thrombosis 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. Prior to the cerebral infarction, the child’s D-dimer was elevated (82 nmol/L, normal range: 1.5 - 4.2).
Additional clinical findings included a minor elevation of liver enzymes. The etiology of the cerebral infarction was unclear but attribution to LENMELDY cannot be ruled out. No other events related to cerebral infarction have been reported during the clinical development of LENMELDY.
Some children received anti-thrombotic prophylaxis [ see Clinical Trials Experience (6.1) ]. Evaluate the risk factors for thrombosis prior to and after LENMELDY infusion according to best clinical practice.
5.2Encephalitis Treatment with LENMELDY may increase the risk of encephalitis. A child with ESEJ MLD developed a serious event of encephalitis after treatment with LENMELDY. At the time of treatment, GMFC-MLD was Level 1 (able to walk independently with impaired gait).
One month after treatment, the child experienced subacute neurological deterioration, with asthenia, hypotonia, cognitive and behavioral problems, vomiting, and swallowing disturbance. The child was afebrile, blood and CSF cultures were negative for bacterial infection, a large viral panel was negative and all routine laboratory tests were normal. The child was treated with plasmapheresis, immunoglobulin and rituximab leading to clinical improvement.
Five months after onset of symptoms the child had reached GMFC-MLD Level 4 (walking not possible; able to sit without support and locomotion possible, or unable to sit without support but locomotion is possible). The child was subsequently treated with eculizumab and tocilizumab. The etiology of this event is unclear but attribution to LENMELDY cannot be ruled out.
Treatment with LENMELDY may trigger a relapsing-remitting pattern of disease progression. No other events related to encephalitis have been reported during the clinical development of LENMELDY. Monitor children for signs or symptoms of encephalitis after LENMELDY treatment.
5.3Serious Infection In the period between start of conditioning and within one year after LENMELDY treatment, severe Grade 3 infections occurred in 39% of all children (21% bacterial, 5% viral, 5% bacterial and viral or bacterial and fungal, and 8% unspecified). The most common Grade 3 infections were device related infections (18%) (including two events of sepsis), respiratory tract infections (including 1 Grade 3 event of pneumonia) (8%), and gastroenteritis/enteritis (8%). Grade 3 febrile n…
🤒 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.
6.1Clinical 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 eve…
🔄 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 )
7.1Vaccines 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.
7.2Anti-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.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy 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.
8.2Lactation 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.
8.3Females and Males of Reproductive Potential Pregnancy Testing As a precautionary measure, a negative serum pregnancy test must be confirmed prior to the start of mobilization and re-confirmed prior to conditioning procedures and before administration of LENMELDY in females of childbearing potential. Contraception Males capable of fathering a child and females of childbearing age should use an effective method of contraception from start of mobilization through at least 6 months after administration of LENMELDY. Infertility There are no data on the effects of LENMELDY on fertility.
Data are available on the risk of infertility with myeloablative conditioning. In clinical trials of LENMELDY, seven children (50% of females) developed ovarian failure. Advise children of the option to cryopreserve semen or ova before treatment, if appropriate.
8.4Pediatric Use The safety and efficacy of LENMELDY has been established in children with PSLI, PSEJ and ESEJ MLD. The clinical trials of LENMELDY treated 20 PSLI, 7 PSEJ, and 10 ESEJ MLD children who received LENMELDY between ages 8 – 19 months (median age of 12 months), 11 months – 5.56 years (median age of 2.57 years), and 2.54 – 11.64 years (median age of 5.84 years), respectively. The safety and efficacy of LENMELDY have not yet been established in children with the late juvenile form of the disease [ see Clinical Studies (14) ].
8.6Patients Seropositive for Human Immunodeficiency Virus (HIV) or other infectious diseases LENMELDY has not been studied in children with HIV-1, HIV-2, HTLV-1, HTLV-2, HBV, HVC, or mycoplasma infection. Negative serology tests for HIV-1/2, HTLV-1/2, HBV, HCV, and a negative test for mycoplasma are necessary to ensure acceptance of apheresis material for LENMELDY manufacturing.
8.7Renal Impairment LENMELDY has not been studied in children with renal impairment. Children should be assessed for renal impairment to ensure HSC transplantation is appropriate.
8.8Hepatic Impairment LENMELDY has not been studied in children with hepatic impairment. Children should be assessed for hepatic impairment to ensure HSC transplantation is appropriate.
🤰 Pregnancy ▾
8.1Pregnancy 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.
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and efficacy of LENMELDY has been established in children with PSLI, PSEJ and ESEJ MLD. The clinical trials of LENMELDY treated 20 PSLI, 7 PSEJ, and 10 ESEJ MLD children who received LENMELDY between ages 8 – 19 months (median age of 12 months), 11 months – 5.56 years (median age of 2.57 years), and 2.54 – 11.64 years (median age of 5.84 years), respectively. The safety and efficacy of LENMELDY have not yet been established in children with the late juvenile form of the disease [ see Clinical Studies (14) ].
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action 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. Functional ARSA enzyme can breakdown or prevent the harmful accumulation of sulfatides.
12.2Pharmacodynamics Deficiency of ARSA is known to be the cause of MLD; therefore, ARSA activity in peripheral blood mononuclear cells of the hematopoietic lineage (i.e. ARSA in PBMC) was evaluated to provide evidence of pharmacodynamic activity of LENMELDY. Median ARSA activity in PBMCs was at supranormal levels by 3 months post-treatment in the PSLI and PSEJ populations (normal range for ARSA activity is 31-198 nmol/mg/h) and supranormal median levels were sustained throughout the duration of follow-up (Table 3).
In ESEJ median ARSA activity was within normal range from Month 3 to Year 2 and supranormal activity was achieved at Year 3 and 5 (Table 3). Table 3: Summary of ARSA Activity (nmol/mg/h) in Total Peripheral Blood Mononuclear Cells by Visit in the Patients Treated with LENMELDY Visit Variable PSLI (N=20) PSEJ (N=7) ESEJ (N=10) Month 3 Patient Samples, n 18 6 10 -- Median (Min, Max) 682 (61, 3398) 1140 (314, 1300) 210 (50, 426) Month 6 Patient Samples, n 16 6 7 One value was below the lower limit of quantification (LLQ) or not detected or not quantifiable, and has been imputed as the LLQ (26 nmol/mg/h).
Normal range for ARSA activity is 31-198 nmol/mg/h. ARSA=Arylsulfatase A; Max=Maximum; Min=Minimum. Number of children at timepoint represents the number of children with non-missing data (including those with imputed values). -- Median (Min, Max) 1095 (37, 2716) 983 (150, 1804) 107 (26, 444) Year 1 Patient Samples, n 20 7 8 -- Median (Min, Max) 1239 (46, 6467) 883 (272, 1976) 130 (55, 688) Year 2 Patient Samples, n 18 6 7 -- Median (Min, Max) 935 (26, 5935) 1063 (328, 2205) 82 (70, 219) Year 3 Patient Samples, n 18 4 6 -- Median (Min, Max) 1558 (26, 7091) 1156 (537, 2173) 234 (30, 1271) Year 5 Patient Samples, n 9 0 3 -- Median (Min, Max) 756 (28, 3474) - 363 (282, 793)
12.3Pharmacokinetics 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.
12.6Immunogenicity During the clinical development program, anti-ARSA antibodies (AAA) were reported in 6/39 children (5 PSLI and 1 PSEJ) with titers between 1:80 and 1:6400. Five events resolved between Days 45 and 368, of which two resolved spontaneously. One event was reported as ongoing.
One child reported declining ARSA levels in the setting of AAA but the impact on clinical efficacy is unknown as the child is still in the pre-symptomatic phase of the disease. Four children received treatment with rituximab. There is insufficient information to characterize the impact of AAA on ARSA activity in PBMC, clinical efficacy, or safety.
🧬 Mechanism of Action ▾
12.1Mechanism of Action 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. Functional ARSA enzyme can breakdown or prevent the harmful accumulation of sulfatides.
📦 How Supplied / Storage and Handling ▾
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.
📋 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 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.
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Ensure that patients and/or caregivers understand the risk of manufacturing failure. A collection of unmanipulated back-up CD34 + cells is required in case of manufacturing failure. These cells must be collected from the patient and be cryopreserved prior to myeloablative conditioning [ see Preparation before LENMELDY Infusion (2.2) ].
Prior to treatment, advise patients and/or caregivers of the following: Risks associated with mobilization and myeloablative conditioning agents [ see Preparation before LENMELDY Infusion (2.2) , Use in Specific Populations ( 8.1 , 8.3 ) ]. Risk of Hypersensitivity Reactions - Although no cases have been reported to date, allergic reactions may occur with the infusion of LENMELDY. The dimethyl sulfoxide (DMSO) in LENMELDY may cause hypersensitivity reactions, including anaphylaxis [ see Warnings and Precautions (5.4) ].
After treatment, advise patients and/or caregivers of the following: Thrombosis and Thrombotic Event -A risk of blood clots may occur. Monitor patients for signs and symptoms of thrombosis [ see Warnings and Precautions (5.1) ]. Encephalitis - Monitor patients for signs or symptoms of encephalitis, including neurological deterioration such as weakness, decreased muscle tone, cognitive deterioration, behavioral problems, vomiting, and swallowing difficulties [ see Warnings and Precautions (5.2) ].
Serious Infection - Life-threatening bacterial and viral infections may occur. Monitor patients for signs and symptoms of infection [ see Warnings and Precautions (5.3) ]. Veno-occlusive Disease - Blood sampling will occur before and after LENMELDY infusion to monitor for liver problems including severe, life threatening, veno-occlusive disease [ see Warnings and Precautions (5.4) ].
Delayed Platelet Engraftment - A risk of bleeding exists after myeloablative conditioning and before platelet engraftment and may continue after engraftment in patients who have continued thrombocytopenia [ see Warnings and Precautions (5.5) ]. Neutrophil Engraftment Failure - There is a potential risk of neutrophil engraftment failure and the need for rescue treatment with their back-up collection of CD34 + cells [ see Warnings and Precautions (5.6) ]. Insertional Oncogenesis - There is a potential risk of insertional oncogenesis after treatment with LENMELDY.
Patients should be monitored lifelong. Monitoring will include assessment for hematologic malignancies annually for at least 15 years after treatment with LENMELDY. This will include integration site analysis as warranted [ see Warnings and Precautions (5.7) ].
Advise patients and/or caregivers to seek immediate attention for the following: Signs of a blood clot, which may include pain, discoloration, or swelling of an arm, legs or feet, with warmth over the affected area, unexplained shortness of breath, acute chest pain or discomfort that worsens on deep breathing, unexplained rapid pulse, numbness or weakness on one side of the body [ see Warnings and Precautions (5.1) ]. New or worsening bleeding or bruising. Platelet recovery following LENMELDY infusion could be delayed, potentially resulting in an increased risk of bruising or bleeding until platelet recovery has been achieved [ see Warnings and Precautions (5.5) ].
Advise patients and/or caregivers to: Monitor for signs and symptoms of bleeding and have frequent blood draws for platelet counts, until platelet recovery has been achieved [ see Warnings and Precautions (5.5) ]. Have their treating physician contact Orchard Therapeutics at 1-888-878-0185 if they are diagnosed with a malignancy [ see Warnings and Precautions (5.7) ] or a blood clot [ see Warnings and Precautions (5.3) ]. Advise patients and/or caregivers that patients should not donate blood, organs, tissues, or cells at any time in the future [ see Dosage and Administration (2.3) ].
Advise patients and/or caregivers that treatment with LENMELDY may cause a false-positive human immunodeficiency viru…