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.
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 * […]