Casgevy · 4.1 Therapeutic indications · 1

HOS-100043 · has-adverse-reaction-information · PDF-Seite 10

Summary of the safety profile The safety of Casgevy was evaluated in two open-label, single-arm studies (study 111 and study 121) and one long-term follow-up study (study 131), in which 97 adolescent and adult patients with TDT or SCD were treated with Casgevy. Treatment with Casgevy was preceded by peripheral blood mobilisation with granulocyte colony-stimulating factor (G-CSF) and plerixafor in patients with TDT and plerixafor only in patients with SCD, followed by apheresis and myeloablative conditioning with busulfan. The safety profile was generally consistent with that expected from busulfan myeloablative conditioning and HSC transplant after mobilisation and apheresis. The median (min, max) duration of follow-up after being administered Casgevy was 22.8 (2.1, 51.1) months for patients with TDT (N=54), and 17.5 (1.2, 46.2) months for patients with SCD (N=43). Serious adverse reactions attributed to Casgevy occurred in 2 (3.7%) patients with TDT: 1 (1.9%) patient with haemophagocytic lymphohistiocytosis, acute respiratory distress syndrome, idiopathic pneumonia syndrome, and headache; 1 (1.9%) patient with delayed engraftment and thrombocytopenia. No patient with SCD had serious adverse reactions attributed to Casgevy. A life-threatening serious adverse reaction of cerebellar haemorrhage occurred in 1 (1.9%) patient with TDT and was attributed to busulfan myeloablative conditioning. One (2.3%) patient with SCD died due to a COVID-19 infection and subsequent respiratory failure. The event was not related to Casgevy. 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 to < 1/10). Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness. Tables 1, 2, 3, and 4 are lists of adverse reactions attributed to mobilisation/apheresis with G-CSF and plerixafor, mobilisation/apheresis with plerixafor only, myeloablative conditioning with busulfan, and Casgevy, respectively, experienced by patients with TDT and SCD in clinical studies with Casgevy. Table 1: Adverse reactions attributed to mobilisation/apheresis in patients with TDT receiving G-CSF and plerixafor (N=59) System organ class (SOC) Very common Common Blood and lymphatic system Leukocytosis, thrombocy

Auszug; vollständigen Abschnitt im Original lesen.

HOS-100039 · has-contraindication-information · PDF-Seite 6

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Contraindications to mobilisation and myeloablative conditioning medicinal products must be considered.

HOS-100038 · has-indication-information · PDF-Seite 3

β-thalassemia Casgevy is indicated for the treatment of transfusion-dependent β-thalassemia (TDT) in patients 12 years of age and older for whom haematopoietic stem cell (HSC) transplantation is appropriate and a human leukocyte antigen (HLA)-matched related HSC donor is not available. Sickle cell disease Casgevy is indicated for the treatment of severe sickle cell disease (SCD) in patients 12 years of age and older with recurrent vaso-occlusive crises (VOCs) for whom haematopoietic stem cell (HSC) transplantation is appropriate and a human leukocyte antigen (HLA)-matched related HSC donor is not available.

HOS-100041 · has-interaction-information · PDF-Seite 8

The drug-drug interaction of mobilisation and myeloablative conditioning medicinal products must be considered. No formal drug interaction studies have been performed. Casgevy is not expected to interact with the hepatic cytochrome P-450 family of enzymes or drug transporters. Use of hydroxyurea/hydroxycarbamide must be discontinued at least 8 weeks prior to start of mobilisation and conditioning. There is no experience on the use of hydroxyurea/hydroxycarbamide after Casgevy infusion. Discontinue the use of voxelotor and crizanlizumab at least 8 weeks prior to start of mobilisation and conditioning, as their interaction potential with mobilisation and myeloablative conditioning medicinal products is not known. Iron chelators must be discontinued at least 7 days prior to initiation of myeloablative conditioning, due to potential interaction with the conditioning medicinal product. Some iron chelators are myelosuppressive. Avoid the use of non-myelosuppressive iron chelators for at least 3 months and use of myelosuppressive iron chelators for at least 6 months after Casgevy infusion. Phlebotomy can be used instead of iron chelation, when appropriate. Live vaccines The safety of immunisation with live viral vaccines during or following Casgevy treatment has not been studied. As a precautionary measure, vaccination with live vaccines is not recommended for at least 6 weeks prior to the start of the conditioning regimens, during Casgevy treatment, and until haematological recovery following treatment. 8

HOS-100042 · has-pregnancy-information · PDF-Seite 9

Women of childbearing potential/Contraception in males and females A negative serum pregnancy test must be confirmed prior to the start of each mobilisation cycle and re-confirmed prior to myeloablative conditioning. There are insufficient exposure data to provide a precise recommendation on duration of contraception following treatment with Casgevy. Women of childbearing potential and men capable of fathering a child must use effective method of contraception from start of mobilisation through at least 6 months after administration of myeloablative conditioning. Please also refer to the Summary of Product Characteristics for the myeloablative conditioning medicinal product. Pregnancy There are no clinical data from the use of exagamglogene autotemcel in pregnant women. No animal reproductive and developmental toxicity studies have been conducted with exagamglogene autotemcel to assess whether it can cause foetal harm when administered to a pregnant woman. It is not known whether exagamglogene autotemcel has the potential to be transferred to the foetus. Casgevy must not be administered during pregnancy because of the risk associated with myeloablative conditioning. Pregnancy after Casgevy infusion should be discussed with the treating physician (see guidance on contraception, above). Breast-feeding It is unknown whether exagamglogene autotemcel is excreted in human milk or transferred to the breast-feeding child. There are no data available. Refer to the Summary of Product Characteristics of the mobilisation and myeloablative conditioning medicinal product(s) for guidance on their use during breast-feeding. Because of the potential risks associated with myeloablative conditioning, breast-feeding should be discontinued during conditioning. The decision to breast-feed after Casgevy treatment should be discussed with the treating physician, taking into account the benefit of breast-feeding for the child versus any potential adverse events from Casgevy or from the underlying maternal condition. Fertility There are no data on the effects of exagamglogene autotemcel on human fertility. Effects on male and female fertility have not been evaluated in animal studies. Data are available on the risk of infertility with myeloablative conditioning. It is therefore advised to consider fertility preservation options such as cryopreservation of semen or ova before treatment if possible.

HOS-100040 · has-warning-information · PDF-Seite 6

Warnings and precautions of mobilisation and myeloablative conditioning medicinal products must be considered. 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 medicinal product. Autologous use Casgevy is intended solely for autologous use and must not under any circumstances be administered to other patients. Casgevy must not be administered if the information on the product labels and Lot information sheet (LIS) does not match the patient’s identity. Transmission of an infectious agent Although Casgevy is tested for sterility, mycoplasma and endotoxins, a risk of transmission of infectious agents exists. Healthcare professionals administering Casgevy must, therefore, monitor patients for signs and symptoms of infections after treatment and treat appropriately, if needed. 6 Hypersensitivity reactions There is a potential for hypersensitivity reactions with Casgevy, including due to Cas9. Serious hypersensitivity reactions, including anaphylaxis may occur due to dimethyl sulfoxide (DMSO) or dextran 40 in Casgevy. Patients should be observed closely during and after infusion. Vital signs (blood pressure, heart rate, and oxygen saturation) and the occurrence of any symptoms should be monitored prior to the start of the infusion, and approximately every 30 minutes from when the first vial of Casgevy is infused until 2 hours after the last vial of Casgevy is infused. Potential neutrophil engraftment failure Neutrophil engraftment failure is a potential risk in haematopoietic stem cell transplant, defined as not achieving neutrophil engraftment after Casgevy infusion and requiring use of unmodified rescue CD34+ cells. Patients must be monitored for absolute neutrophil counts (ANC) and infections must be managed according to standard guidelines and medical judgement. In the event of neutrophil engraftment failure, patients must be infused with rescue CD34+ cells (see section 4.8). Delayed platelet engraftment Longer median platelet engraftment times have been observed with Casgevy treatment compared to allogeneic HSC transplantation. There is an increased risk of bleeding until platelet engraftment is achieved. Patients should be monitored for bleeding according to standard guid

Auszug; vollständigen Abschnitt im Original lesen.