LIBMELDY

Libmeldy must be administered in a qualified treatment centre by a physician with experience in Haematopoietic Stem Cell Transplantation (HSCT) and trained for administration and management of patients treated with the medicinal product.

4) and should only be administered once. The dose of Libmeldy must be determined based on the patient’s body weight at the time of infusion. Treatment consists of a single dose for infusion containing a dispersion of viable CD34+ cells in one or more infusion bags.

The minimum recommended dose of Libmeldy is 3 × 106 CD34+ cells/kg of body weight. In clinical studies, doses up to 30 × 106 CD34+ cells/kg have been administered. 6). See the accompanying Lot Information Sheet (LIS) for additional information pertaining to dose.

Peripheral blood mobilisation and apheresis The autologous CD34+ cells are isolated from mobilised peripheral blood (mPB). This is achieved by apheresis procedure(s) following peripheral blood mobilisation. For manufacture of Libmeldy, the patient must be able to donate a minimum of 8-10 ×106 CD34+ cells/kg, considering that the optimal range is between 20- 30 × 106 CD34+ cells/kg.

The minimum CD34+ cell quantity may be achieved using one or more cycles of apheresis. 1). 4). These cells must be collected from the patient and be cryopreserved according to institutional procedures prior to myeloablative conditioning.

The back-up cells may be harvested either through mPB apheresis or bone marrow harvest. 1 for a description of the mobilisation regimen used in clinical studies). 4). 1 for a description of the myeloablative regimen used in clinical studies).

Busulfan is the recommended conditioning medicinal product. Myeloablative conditioning should not begin until the complete set of infusion bag(s) constituting the dose of Libmeldy has been received and stored at the qualified treatment centre, and the availability of the back-up collection is confirmed.

e. transplant-associated thrombotic microangiopathy (TA-TMA) or atypical haemolytic uremic syndrome (aHUS), in line with local guidelines. Depending on the myeloablative conditioning regimen administered, prophylaxis for seizures should also be considered.

Phenytoin is not recommended as it may increase busulfan clearance. Prophylactic and empiric use of anti-infectives (bacterial, fungal, viral) should be considered for the prevention and management of infections especially during the neutropenic period following conditioning.

Summary of the safety profile The safety of Libmeldy was evaluated in 35 patients with MLD. 85 years). Three patients died and a total of 26 patients remained in the follow-up phase. 47 years). 1). Given the small patient population, adverse reactions in the table below do not provide a complete perspective on the nature and frequency of these events.

Treatment with Libmeldy is preceded by medical interventions, namely haematopoietic stem cell collection through peripheral blood mobilisation with G- CSF with or without plerixafor followed by apheresis, and myeloablative conditioning (preferably using busulfan), which carry their own risks.

When assessing the safety of a treatment with Libmeldy, the safety profile and product information of the medicinal products used for peripheral blood mobilisation and myeloablative conditioning should be considered, in addition to the risks linked to the gene therapy.

Tabulated list of adverse reactions Adverse reactions are listed by MedDRA body system organ class and by frequency. Frequencies are defined as: very common (≥1/10), and common (≥1/100 and <1/10). Table 1 Adverse reactions attributed to Libmeldy System Organ Class Very Common Common Immune system disorders Antibody Test Positive (Anti ARSA Antibody) Table 2 Adverse reactions potentially attributed to myeloablative conditioning* System Organ Class Very Common Common Infections and infestations Cytomegalovirus viraemia, Pneumo nia, Staphylococcal infection, Urinary tract infection, Viral infection Blood and lymphatic system disorders Febrile neutropenia, Neutropenia Anaemia, Thrombocytopenia Metabolism and nutrition disorders Metabolic acidosis Fluid overload Psychiatric disorders Insomnia Nervous system disorders Headache Respiratory, thoracic and mediastinal disorders Epistaxis, Oropharyngeal pain Gastrointestin al disorders Stomatitis, Vomiting Ascites, Diarrhoea, Gastrointestinal haemorrhage, Nausea Hepatobiliary disorders Hepatomegal y, Veno- occlusive liver disease Hypertransaminasaemia Skin and subcutaneous tissue disorders Skin exfoliation Musculoskelet al and connective tissue disorders Back pain, Bone pain Renal and urinary Oliguria System Organ Class Very Common Common disorders Reproductive System and Breast Disorders Ovarian failur e General disorders and administration site conditions Pyrexia Investigations Alanine aminotransferase increased, Aspartate aminotransferase increased, Aspergillus test positive * Based on 29 patients who have undergone myeloablative conditioning by busulfan in the integrated data set.

Traceability The traceability requirements of cell-based advanced therapy medicinal products must apply. To ensure traceability, the name of the product, the batch number and the name of the treated patient must be kept for a period of 30 years after expiry date of the product.

Autologous use Libmeldy is intended solely for autologous use and must not, under any circumstances be administered to other patients. Libmeldy must not be administered if the information on the product labels and Lot Information Sheet (LIS) do not match the patient’s identity.

Rapidly progressive phase of the disease Treatment with Libmeldy should be performed before the disease enters its rapidly progressive phase. Eligibility to treatment with Libmeldy should initially be assessed by the treating physician via full neurological examination, motor function assessment and neurocognitive assessment, as appropriate for the patients’ age.

Prior to the commencement of cellular harvest, the treating physician should ensure that the patient has not clinically deteriorated. Thereafter, prior to the commencement of conditioning, the treating physician should ensure that autologous HSPC gene therapy administration remains clinically appropriate for the patient, and that treatment with Libmeldy is still indicated.

Mobilisation and myeloablative conditioning medicinal products Warnings and precautions of the mobilisation and myeloablative conditioning medicinal products must be considered. Central venous catheter (CVC) complications including infections and thromboses Infections related to the use of CVCs have been reported in clinical studies and there is a risk of thrombosis associated with the CVC.

Patients should be closely monitored for potential infections and catheter-related events. Transmission of an infectious agent Although Libmeldy is tested for sterility and mycoplasma, a risk of transmission of infectious agents exists.

1. Previous treatment with haematopoietic stem cells gene therapy. Contraindications to the mobilisation and the myeloablative medicinal products must be considered.