Atidarsagene Autotemcel

Atidarsagene Autotemcel is a prescription medication 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).

• Atidarsagene Autotemcel is available under the following different brand names: Lenmeldy.

Common side effects of Atidarsagene Autotemcel include:

• fever 
• low white blood cell count
• mouth sores
• respiratory infections 
• rash
• medical line infections
• viral infections
• gastrointestinal infections 
• enlarged liver

Serious side effects of Atidarsagene Autotemcel include:

• not available

Rare side effects of Atidarsagene Autotemcel include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Pediatric dosage

Suspension for IV infusion

• 2-11.8 x 106  cells/mL (1.8-11.8 x 106 CD34+ cells/mL) suspended in cryopreservation solution
• Supplied in 1-8 infusion bags

Metachromatic leukodystrophy

Pediatric dosage

• For autologous use only as a one-time single-dose IV infusion
• Confirm availability and storage of Atidarsagene Autotemcel and availability of a backup collection of CD34+ cells before conditioning

Myeloablative conditioning

• Myeloablative conditioning must be administered before Atidarsagene Autotemcel infusion
• Busulfan was used in clinical trials; there are no data available supporting the use of alternative conditioning agents with Atidarsagene Autotemcel
• Do not begin myeloablative conditioning until Atidarsagene Autotemcel has been received and stored at the treatment center and the availability of the backup collection of CD34+ cells has also been confirmed
• After completing myeloablative conditioning, allow a minimum of 24 hours of washout before Atidarsagene Autotemcel infusion
• Minimum and maximum Atidarsagene Autotemcel dose
• Dose calculated based on the child’s weight at the time of infusion

MLD subtype

• PSLI: 4.2-30 x 106 CD34+ cells/kg
• PSEJ: 9-30 x 106 CD34+ cells/kg
• ESEJ: 6.6-30 x 106 CD34+ cells/kg

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Atidarsagene Autotemcel has severe interactions with no other drugs
• Atidarsagene Autotemcel has serious interactions with no other drugs
• Atidarsagene Autotemcel has moderate interactions with no other drugs
• Atidarsagene Autotemcel has minor interactions with no other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Atidarsagene Autotemcel?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Atidarsagene Autotemcel?”

Cautions

• Thrombosis and thromboembolic events
  • Treatment may increase the risk of thrombosis and thromboembolic events
  • Additional clinical findings include a minor elevation of liver enzymes
  • Some children received antithrombotic prophylaxis
  • Evaluate risk factors for thrombosis before and after infusion according to best clinical practice
  • Patients should seek immediate attention if experiencing signs of a blood clot, including 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
• Encephalitis
  • Treatment may increase the risk of encephalitis
  • Monitor children for signs or symptoms of encephalitis after treatment
• Serious infection
  • In the period between the start of conditioning and within 1 year after treatment, severe Grade 3 infections occurred in 39% of all children
  • The most common Grade 3 infections were device-related infections, respiratory tract infections, and gastroenteritis/enteritis
  • Grade 3 febrile neutropenia developed within 1 month after infusion in 82% of children
  • In the event of febrile neutropenia, monitor for signs and symptoms of infection and manage with broad-spectrum antibiotics, fluids, and other supportive care as medically indicated
  • Monitor children for signs and symptoms of infection after myeloablative conditioning and infusion and treat appropriately
  • Administer prophylactic antimicrobials according to best clinical practice
• Veno-occlusive disease (VOD)
  • Monitor children for signs and symptoms of VOD including liver function tests in all children during the first month after infusion
  • Consider prophylaxis with antithrombotic agents based on risk factors for VOD and best clinical practice
• Delayed platelet engraftment
  • Delayed platelet engraftment observed
  • Bleeding risk increased before platelet engraftment and may continue after engraftment in children with prolonged thrombocytopenia
  • All children treated with Atidarsagene Autotemcel received transfusion support with platelets according to best clinical practice
  • Inform caregivers regarding the risk of bleeding until platelet recovery has been achieved
  • Monitor children for thrombocytopenia and bleeding
• Neutrophil engraftment failure
  • Neutrophil engraftment failure is defined as failure to achieve 3 consecutive absolute neutrophil counts (ANC) of more than 500 cells/microliter obtained on different days by Day 60 after Atidarsagene Autotemcel infusion
  • Monitor ANC until engraftment has been achieved
  • If neutrophil engraftment failure occurs, provide rescue treatment with the unmanipulated backup collection of CD34+ cells
• Insertional oncogenesis
  • Potential risk of lentiviral vector-mediated insertional oncogenesis after treatment
  • Children treated may develop hematologic malignancies and should be monitored lifelong
  • Monitor for hematologic malignancies with a complete blood cell count (with differential) annually and integration site analysis as warranted for more than or equal to15 years after treatment
  • If a malignancy occurs, contact Orchard Therapeutics at 1-888-878-0185 for reporting and to obtain instructions on the collection of samples for testing
• Hypersensitivity reactions
  • Potential risk of allergic reactions
  • Dimethyl sulfoxide (DMSO) in products may cause hypersensitivity reactions, including anaphylaxis which is potentially life-threatening and requires immediate intervention
  • Hypersensitivity, including anaphylaxis, can occur in children with and without prior exposure to DMSO
  • In clinical trials, no cases of hypersensitivity reactions have been reported
  • Interference with serology testing
  • Children who have received Atidarsagene Autotemcel are likely to test positive by polymerase chain reaction (PCR) assays for HIV due to lentiviral vector provirus insertion resulting in a false-positive test for HIV
  • Children who have received Atidarsagene Autotemcel should not be screened for HIV infection using a PCR-based assay
• Drug interaction overview
  • Antiretrovirals
    • Avoid
      • Antiretroviral (ART) medications may interfere with the manufacturing of Atidarsagene Autotemcel
      • Do not take ARTs for at least 1 month before cell mobilization or the expected duration for elimination of the medications
      • If a child requires ARTs for HIV prevention, delay Atidarsagene Autotemcel initiation until confirmation of a negative test for HIV
  • Vaccines
    • Avoid
      • Safety and effectiveness of vaccination during or following Atidarsagene Autotemcel treatment have not been studied
      • Vaccination is not recommended for 6 weeks preceding the start of myeloablative conditioning, and until hematologic recovery following treatment
      • Where feasible, administer childhood vaccinations before myeloablative conditioning

Pregnancy and Lactation

• There is no clinical data on pregnant women
• No animal reproductive and developmental toxicity studies have been conducted to assess whether it can cause fetal harm when administered to a pregnant woman
• Must not be administered during pregnancy because of risk associated with myeloablative conditioning
• As a precautionary measure, a negative serum pregnancy test must be confirmed before the start of mobilization and reconfirmed before conditioning procedures and before administration to women of childbearing potential
• Contraception
  • Men capable of fathering a child and women of childbearing age should use an effective method of contraception from the start of mobilization through more than 6 months after administration
• Infertility
  • Data are not available on the effects of Atidarsagene Autotemcel on fertility
  • Data are available on the risk of infertility with myeloablative conditioning
  • In clinical trials, 7 children (50% of women) developed ovarian failure; advise children of the option to cryopreserve semen or ova before treatment, if appropriate
• Lactation
  • Data are not available on the presence of Atidarsagene Autotemcel in human or animal milk, its effects on breastfed children, or on milk production
  • Because of potential risks associated with myeloablative conditioning, breastfeeding should be discontinued during conditioning
  • Breastfeeding after 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