Lenmeldy

Lenmeldy

Lenmeldy

What is Lenmeldy?

FDA approval for Lenmeldy was granted on March 18, 2024. Lenmeldy is indicated for the treatment of children with presymptomatic late juvenile leukodystrophy (MLD) or presymptomatic late juvenile leukodystrophy (PSLI). .

What is Metachromatic Leukodystrophy?

Metachromatic leukodystrophy is a rare and serious genetic disorder that affects the brain and nervous system. Metachromatic leukodystrophy is caused by a faulty gene, meaning the body doesn't produce enough of an enzyme called arylsulfatase A (ARSA). This lack of ARSA causes fatty substances called sulfatides to build up in the brain and nerves, causing problems with the ability to move and think, severe spasticity, seizures, and causes patients to gradually lose their ability to move, speak, swallow, eat and see. Lenmeldy therapy replaces the faulty gene in the stem cells with an effective gene so that the body is now able to produce the ARSA enzyme, which helps break down the harmful buildup of sulfatides and stop the progression of MLD.

How does Lenmeldy work?

Lenmeldy therapy begins with a treatment called hematopoietic stem cell (HSC) mobilization. This involves giving the patient a drug that helps transport stem cells from the bone marrow into the blood so they can be collected. The stem cells are then genetically modified to contain working copies of the ARSA gene. This is the Lenmeldy infusion. Before receiving the Lenmeldy infusion, the patient will receive chemotherapy (myeloablative conditioning) to remove cells from the bone marrow to make room for the new, modified stem cells. Lenmeldy then receives a one-time, single-dose infusion, and the newly modified stem cells attach to the bone marrow and multiply there. The newly modified stem cells allow the body to produce the ARSA enzyme, which helps break down the harmful buildup of sulfatides and stop the progression of MLD.

Lenmeldy side effects

The most common adverse reactions with Lenmeldy were fever with low neutrophil count (85%), mouth sores (77%), respiratory tract infections (54%), rash (33%), device-related infections (31%), other viral infections (28%), fever (21%), gastroenteritis (21%), and enlarged liver (18%). These are adverse reactions that occurred in 10% or more of all children within one year of treatment and do not include laboratory adverse reactions.

The most common laboratory abnormalities in Lenmeldy were elevated D-dimer (67%), neutropenia (28%), and elevated liver enzymes (23%).

Other clinically significant adverse reactions are listed in the “Warnings” section.

warning

Thrombosis and thromboembolic events:Assess risk factors for thrombosis before and after infusion. Consider prophylaxis with antithrombotics prior to stem cell infusion.

Inflammation of the brain (encephalitis): Children should be monitored for signs or symptoms of encephalitis after treatment.

Severe infection:Monitor children for serious infections.

Small blood vessels leading to and located in the liver become blocked (veno-occlusive disease):Monitor children for signs and symptoms of VOD during the first month after treatment, including liver function tests in all patients, and consider prophylaxis for VOD.

Delayed platelet transplantation:Monitor children for thrombocytopenia and bleeding until platelet recovery is achieved.

Risk of Neutrophil Transplantation Failure:Monitor absolute neutrophil count (ANC) post-infusion. If neutrophil transplantation does not occur, administer replacement cells.

Risk of inserted oncogenesis:Monitor children for hematologic malignancies annually after treatment.

Risk of hypersensitivity reactions:Monitor for hypersensitivity reactions during infusion.

Antiretroviral use:Children should not take prophylactic HIV antiretroviral medications for at least one month before mobilization or for the expected period necessary for drug elimination. Antiretroviral drugs may affect the production of Lenmeldy. If a child requires antiretroviral medications for HIV prophylaxis, initiation of treatment should be delayed until a negative HIV test is confirmed.

Interference with serological tests:Children who have received this stem cell infusion are likely to test positive for HIV on polymerase chain reaction (PCR) tests due to the insertion of the LVV provirus, resulting in a false positive test for HIV. Therefore, children who have received Lenmeldy should not be tested for HIV infection using a PCR-based test.

Before you take this medicine

Before your child is given Lenmeldy, the doctor will:

• Überprüfen Sie die Lunge, das Herz, die Niere, die Leber und den Blutdruck Ihres Kindes.
• Achten Sie auf Anzeichen einer Infektion; Jede Infektion wird behandelt, bevor Ihrem Kind dieses Arzneimittel verabreicht wird.
• Überprüfen Sie, ob Hepatitis B, Hepatitis C, das humane T-Zell-Lymphotrophe Virus (HTLV), das Cytomegalievirus (CMV), HIV oder eine Mykoplasmeninfektion vorhanden sind.
• Prüfen Sie, ob Ihr Kind in den letzten 6 Wochen eine Impfung erhalten hat oder ob eine Impfung in den nächsten Monaten geplant ist.

Lenmeldy is made from your child's stem cells and should only be given to your child.

How do I get Lenmeldy?

Lenmeldy is administered as a single, single-dose intravenous infusion.

Before the infusion can be given, the patient will receive treatments to prepare for the Lenmeldy infusion and to prepare the body for the infusion. First, the patient receives treatment to mobilize their stem cells, which are collected. The patient then receives chemotherapy to prepare the bone marrow and then their own Lenmeldy infusion.

The child may only receive Lenmeldy made from the child's own stem cells.

Lenmeldy dosage information

The dosage of Lenmeldy infusion depends on the subtype of the child's MLD disease and the child's weight.

Interactions

Tell your doctor if your child is taking, has recently taken or might take any other medicines or vaccines.

• Impfungen werden in den 6 Wochen vor Beginn der myeloablativen Konditionierung und bis zur hämatologischen Erholung nach der Behandlung mit Lenmeldy nicht empfohlen.
• Ihr Kind sollte mindestens einen Monat vor den Mobilisierungsmedikamenten bzw. für die voraussichtliche Dauer der Eliminierung der Medikamente keine antiretroviralen Medikamente einnehmen, da die antiretroviralen Medikamente die Herstellung von Lenmeldy beeinträchtigen können.

Manufacturer

Manufactured for: Orchard Therapeutics North America Boston, MA 02210

References

1. Lenmeldy-Packungsbeilage FDA
2. FDA genehmigt erste Gentherapie für Kinder mit metachromatischer Leukodystrophie
3. Was ist metachromatische Leukodystrophie?

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