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Casgevy is a brand name for Exagamglogene Autotemcel. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: 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…
Verbatim from this product's EMA label. Tap a section to expand.
Casgevy must be administered in an authorised treatment centre by a physician with experience in HSC transplantation and in the treatment of patients with β-haemoglobinopathies and trained for administration and management of patients treated with the medicinal product.
Before mobilisation, apheresis and myeloablative conditioning are initiated, confirm that haematopoietic stem cell transplantation is appropriate for the patient. 4). Treatment consists of a single dose containing a dispersion for infusion of viable CD34+ cells in one or more vials.
The minimum recommended dose of Casgevy is 3 × 106 CD34+ cells/kg of body weight. See the accompanying Lot information sheet (LIS) for additional information pertaining to dose. Mobilisation and apheresis Patients are required to undergo CD34+ HSPC mobilisation followed by apheresis to isolate the CD34+ cells for medicinal product manufacturing.
Maximise CD34+ cell collection for product manufacturing during each mobilisation and apheresis cycle. Perform two consecutive days of cell collection for product manufacturing per cycle, if clinically tolerated. A total collection target of at least 20 × 106 CD34+ cells/kg is recommended for product manufacture.
Collected cells should be sent for product manufacturing even if the total collection target is not achieved. In addition, at least 2 × 106 CD34+ cells/kg are required to be collected for back-up unmodified rescue cells. A third day of cell collection can be used to obtain back-up rescue cells, if needed.
If the minimum dose of Casgevy is not met after initial medicinal product manufacturing, the patient will need to undergo additional cycles of mobilisation and apheresis to obtain more cells for additional product manufacture. Each mobilisation and apheresis cycle must be separated by a minimum of 14 days.
4 The back-up collection of ≥ 2 × 106 CD34+ cells/kg of unmodified rescue cells must be collected from the patient and be cryopreserved prior to myeloablative conditioning and infusion with Casgevy. The unmodified cells may be needed for rescue treatment under any one of the following conditions: compromise of Casgevy after initiation of myeloablative conditioning and before Casgevy infusion; neutrophil engraftment failure; or loss of engraftment after infusion with Casgevy.
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. 2) months for patients with SCD (N=43). 9%) patient with delayed engraftment and thrombocytopenia.
No patient with SCD had serious adverse reactions attributed to Casgevy. 9%) patient with TDT and was attributed to busulfan myeloablative conditioning. 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 disorders Leukocytosis, thrombocytopenia Metabolism and nutrition disorders Hypokalaemia Nervous system disorders Headache Respiratory, thoracic and mediastinal disorders Oropharyngeal pain Gastrointestinal disorders Nausea Abdominal pain, vomiting, diarrhoea, oral hypoaesthesia Musculoskeletal and connective tissue disorders Musculoskeletal pain * 11 General disorders and administration site conditions Pain, pyrexia * Musculoskeletal pain included back pain, bone pain, musculoskeletal chest pain, neck pain, non-cardiac chest pain, pain in extremity.
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.
7 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. 8). Delayed platelet engraftment Longer median platelet engraftment times have been observed with Casgevy treatment compared to allogeneic HSC transplantation.
1. Contraindications to mobilisation and myeloablative conditioning medicinal products must be considered.
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1 for a description of the mobilisation regimen used in the clinical study. Refer to the Summary of Product Characteristics for the mobilisation medicinal product(s) prior to treatment with Casgevy. β-thalassemia Prior to apheresis procedure it is recommended that patients receive red blood cell (RBC) transfusion(s) with a goal to maintain total haemoglobin (Hb) concentration ≥ 11 g/dL.
Sickle cell disease Prior to apheresis it is recommended that patients receive RBC exchange or simple transfusion(s) with a goal of maintaining haemoglobin S (HbS) levels < 30% of total Hb while keeping total Hb concentration ≤ 11 g/dL.
, hydroxyurea/hydroxycarbamide, crizanlizumab, voxelotor) must be discontinued 8 weeks before the planned start of mobilisation and conditioning. Granulocyte colony stimulating factor (G-CSF) must not be administered for mobilisation in patients with sickle cell disease.
Pre-treatment conditioning Full myeloablative conditioning must be administered before infusion of Casgevy. Conditioning must not be initiated until the complete set of vials constituting the full dose of Casgevy has been received at the authorised treatment centre, and the availability of the back-up collection of unmodified CD34+ cells is confirmed.
1 for a description of the conditioning regimen used in the clinical study. Refer to the Summary of Product Characteristics for the myeloablative conditioning medicinal product(s) prior to treatment. β-thalassemia It is recommended that patients maintain total Hb concentration ≥ 11 g/dL for 60 days prior to myeloablative conditioning.
Sickle cell disease It is recommended that patients receive RBC exchange or simple transfusion(s) for at least the 8 weeks prior to the initiation of myeloablative conditioning with a goal of maintaining HbS levels < 30% of total Hb while keeping total Hb concentration ≤ 11 g/dL.
, hydroxyurea/hydroxycarbamide, crizanlizumab, voxelotor). Iron chelation therapy must be stopped at least 7 days prior to myeloablative conditioning. Prophylaxis for seizures should also be considered. Refer to the Summary of Product Characteristics for the myeloablative conditioning medicinal product used for information on drug interactions.
Prophylaxis for hepatic veno-occlusive disease (VOD)/hepatic sinusoidal obstruction syndrome should be considered, per institutional guidelines. 5 Prior to starting the myeloablative conditioning regimen, confirm availability of the complete set of vials constituting the dose of Casgevy, and unmodified rescue cells.
See the Lot information sheet (LIS) provided with the product shipment for confirmation of the number of vials and total dose of Casgevy. Pre-medication It is recommended that pre-medication with paracetamol and diphenhydramine, or equivalent medicinal products, be administered per institutional guidelines, before the infusion of Casgevy, to reduce the possibility of an infusion reaction.
Special populations Patients aged 35 years and older Casgevy has not been studied in patients > 35 years of age. The safety and efficacy of Casgevy in this population has not been established. The benefit of treatment in individual patients should be considered against the risks of HSC transplantation.
73 m2. No dose adjustment is required. Hepatic impairment Casgevy has not […]
Table 2:
Adverse reactions attributed to mobilisation/apheresis in patients with SCD receiving plerixafor (N=58) System organ class (SOC) Very common Common Blood and lymphatic system disorders Sickle cell anaemia with crisis Metabolism and nutrition disorders Hyperphosphataemia, hypomagnesaemia Nervous system disorders Headache Respiratory, thoracic and mediastinal disorders Acute chest syndrome Gastrointestinal disorders Abdominal pain *, nausea, Vomiting Diarrhoea Musculoskeletal and connective tissue disorders Musculoskeletal pain † Arthralgia General disorders and administration site conditions Pain, fatigue * Abdominal pain included abdominal pain upper.
† Musculoskeletal pain included back pain, bone pain, chest pain, neck pain, non-cardiac chest pain, and pain in extremity.
Table 3:
Adverse reactions attributed to myeloablative conditioning with busulfan in patients with TDT and SCD (N=97) * System organ class (SOC) Very common Common Infections and infestations Pneumonia, sepsis, klebsiella sepsis, oral candidiasis, folliculitis Blood and lymphatic system disorders Thrombocytopenia, febrile neutropenia, neutropenia, anaemia, lymphopenia †, leukopenia Pancytopenia, reticulocytopenia, splenomegaly Metabolism and nutrition disorders Decreased appetite, hypokalaemia, hyperphosphataemia, hypomagnesaemia, fluid retention, hypophosphataemia Hypoalbuminaemia, hypocalcaemia Nervous system disorders Headache Cerebellar haemorrhage, hydrocephalus, peripheral sensory neuropathy, peripheral neuropathy, neuralgia, dysgeusia Eye disorders Vision blurred, dry eye Cardiac disorders Tachycardia Vascular disorders Hypotension, hot flush Respiratory, thoracic and mediastinal disorders Epistaxis, oropharyngeal pain Respiratory failure, idiopathic pneumonia syndrome, hypoxia, dyspnoea, cough Gastrointestinal disorders Mucositis ‡, nausea, vomiting, abdominal pain §, diarrhoea, constipation, gastritis Colitis, dyspepsia, gingival bleeding, gastrooesophageal reflux disease, haematemesis, oesophagitis, dysphagia, gastrointestinal inflammation, haematochezia, mouth ulceration Hepatobiliary disorders Veno-occlusive liver disease, hyperbilirubinaemia, alanine aminotransferase increased Aspartate aminotransferase increased, hepatomegaly, gamma-glutamyltransferase increased 12 System organ class (SOC) Very common Common Skin and subcutaneous tissue disorders Pigmentation disorder #, skin exfoliation, alopecia, petechiae, dry skin, rash ** Pruritus, erythema Musculoskeletal and connective tissue disorders Musculoskeletal pain †† Arthralgia Renal and urinary disorders Dysuria, haematuria Reproductive system and breast disorders Amenorrhoea, intermenstrual bleeding, vulvovaginal pain, dysmenorrhoea, menstruation irregular, premature menopause General disorders and administration site conditions Pyrexia, fatigue Pain Investigations Weight decreased International normalised ratio increased, C-reactive protein increased, weight increased Injury, poisoning procedural complications Delayed engraftment, subcutaneous haematoma, skin abrasion, skin laceration * […]
There is an increased risk of bleeding until platelet engraftment is achieved. Patients should be monitored for bleeding according to standard guidelines and medical judgement. Frequent platelet counts must be conducted until platelet engraftment and platelet recovery are achieved.
8). Risk of insufficient mobilisation/apheresis in patients with SCD Patients with SCD may require more cycles of mobilisation and apheresis compared to patients with TDT and are at higher risk of failure of sufficient mobilisation/apheresis.
2 for the recommended total CD34+ cell collection target. 1 for information regarding the average number of cycles of mobilisation and apheresis, and overall discontinuation rates. Gene-editing related oncogenesis No cases of myelodysplasia, leukaemia, or lymphoma have been reported in clinical studies with Casgevy.
There is a theoretical risk of oncogenesis related to gene editing. Patients should be monitored at least annually (including complete blood count) for 15 years after treatment with Casgevy. If myelodysplasia, leukaemia, or lymphoma are detected, the local representative of the Marketing Authorisation Holder should be contacted to determine appropriate samples for analysis.
The risk of unintended, off-target editing in an individual’s edited CD34+ cells cannot be ruled out. A search spanning the human genome identified off-target editing at a single variant site. 3% (3/91) of patient samples analyzed (edited CD34+ cells).
3). Immunogenicity No immune-mediated reactions were observed in clinical studies with Casgevy. It is unknown whether pre-formed antibodies to Cas9 including following recent Streptococcus pyogenes infection could result in immune-mediated reactions and/or clearance of cells with residual Cas9.
Blood, organ, tissue, and cell donation Patients treated with Casgevy must not donate blood, organs, tissues, and cells for transplantation. Long-term follow-up Patients must be monitored annually (including complete blood counts) according to standard guidelines and medical judgement.
Patients are expected to be enrolled in a long-term follow-up scheme in order to better understand the long-term safety and efficacy of Casgevy. 3 mg to 70 mg sodium in each vial. 3 to 4% of the WHO recommended maximum daily intake of 2 g sodium for an adult.