Strimvelis · 4.5 Interaction with other medicinal products and other forms of interaction · 1

HOS-097251 · has-adverse-reaction-information · PDF-Seite 7

Summary of the safety profile Serious adverse reactions include T-cell type acute leukaemia and autoimmunity (e.g. autoimmune haemolytic anaemia, autoimmune aplastic anaemia, autoimmune hepatitis, autoimmune thrombocytopenia and Guillain-Barré syndrome). The most commonly reported adverse reaction was pyrexia. Tabulated list of adverse reactions The safety of Strimvelis was evaluated in 33 subjects i.e. 22 patients treated in the clinical development program and 11 patients treated in the commercial setting, with a median duration of follow-up of 12 years for patients treated in clinical studies and 1.5 years for patients treated in the commercial setting. Given the small patient population and size of the cohorts, adverse reactions in the table below may not provide a complete perspective on the nature and frequency of these events. Adverse reactions are listed below by MedDRA body system organ class and by frequency. The frequency categories used are: very common (>1/10), and common (1/100 to <1/10). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. System organ class Very common Common Blood and lymphatic system Anaemiaa, Autoimmune haemolytic disorders Neutropeniaa anaemia, Autoimmune aplastic anaemia, Autoimmune thrombocytopenia Neoplasms, benign, malignant T-cell type acute and unspecified leukaemia Endocrine disorders Hypothyroidism Autoimmune thyroiditis Nervous system disorders Guillain-Barré syndrome Vascular disorders Hypertensiona Respiratory, thoracic and Asthma, mediastinal disorders Rhinitis allergic Hepatobiliary disorders Autoimmune hepatitis Skin and subcutaneous tissue Dermatitis atopic, disorders Eczema General disorders and Pyrexia administration site conditions Investigations

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HOS-097247 · has-contraindication-information · PDF-Seite 4

Hypersensitivity to the product or to any of the excipients listed in section 6.1. Current or previous history of leukaemia or myelodysplasia. Positive test for human immunodeficiency virus (HIV) or presence of any other transmissible infectious agent listed in the current EU Cell and Tissue Directive prior to bone marrow harvest. History of previous gene therapy.

HOS-097246 · has-indication-information · PDF-Seite 2

Strimvelis is indicated for the treatment of patients with severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID), for whom no suitable human leukocyte antigen (HLA)- matched related stem cell donor is available (see sections 4.2 and 4.4).

HOS-097249 · has-interaction-information · PDF-Seite 6

No interaction studies have been performed. Strimvelis is not expected to interact with the hepatic cytochrome P-450 family of enzymes or drug transporters. Live vaccines The safety of immunisation with live viral vaccines following Strimvelis treatment has not been studied. Vaccination with live virus vaccines is not recommended during the 6 weeks preceding the start of non- myeloablative conditioning, and until haematological and immunological recovery following treatment with Strimvelis.

HOS-097250 · has-pregnancy-information · PDF-Seite 6

As Strimvelis is not intended for use in adults, human data on use during pregnancy or lactation and animal reproduction studies are not available. With regard to fertility, consult the SmPC of the conditioning medicinal product. It should be noted that the treating physician should inform the patient’s parents/carers about options for cryopreservation of spermatogonial stem cells or ovarian tissue.

HOS-097248 · has-warning-information · PDF-Seite 4

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 should be kept for a period of 30 years after the expiry date of the product. Autologous use Strimvelis is intended solely for autologous use and should never be administered to any patient other than the original CD34+ cell donor. Strimvelis must not be administered if the information on the product labels and Lot Information Sheet (LIS) do not match the patient’s identity. Risk of insertional oncogenesis One case of Lymphoid T cell leukaemia has been reported in a child with ADA-SCID 4.7 years after treatment with Strimvelis (see section 4.8). Patients treated with Strimvelis may develop secondary malignancies. Patients should be monitored life-long for secondary malignancies. In the event that a secondary malignancy occurs, the company should be contacted to obtain instructions on the collection of patient samples for testing. General The long-term effects and durability of response to Strimvelis on ADA-SCID have not been systematically assessed beyond 8 years after treatment (see section 5.1). Non-immunological manifestations of ADA-SCID may not respond to Strimvelis. 4 Cases of skin papillomas, abnormal serum protein electrophoresis and one case each of lipofibroma, pulmonary mass and decreased T-cell V beta repertoire were reported. No evidence of causality of the product has been established. In some cases, the patient may be unable to receive treatment because of manufacturing issues. After notification, the treating physician may need to modify the treatment program of the patient accordingly (i.e. terminating the busulfan conditioning and/or administration of the stem cell back up treatment if appropriate). Warnings and precautions of the myeloablative conditioning medicinal products must be considered. Immune reconstitution During the clinical studies, T-lymphocyte (CD3+) and NK (CD56+) cell counts improved following treatment. Median values at 3-years post gene therapy were below the normal range. Continued follow-up is recommended. Central venous catheter (CVC) complications including infections and thromboses Adverse events related to the use of central venous catheters (CVCs) have been reported (e.g., serious CVC infections and thrombosis in the device). Patients shou

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