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warnings and cautions
5 WARNINGS AND PRECAUTIONS Neutrophil Engraftment Failure: Monitor absolute neutrophil counts (ANC) after CASGEVY infusion. Administer rescue cells in the event of neutrophil engraftment failure. ( 5.1 ) Delayed Platelet Engraftment: Monitor platelet counts until platelet engraftment and recovery are achieved. Patients should be monitored for bleeding. ( 5.2 ) Hypersensitivity Reactions: Monitor for hypersensitivity reactions during and after infusion. ( 5.3 ) Off-Target Genome Editing Risk: The risk of unintended, off-target editing in CD34 + cells due to genetic variants cannot be ruled out. ( 5.4 ) 5.1 Neutrophil Engraftment Failure There is potential risk of neutrophil engraftment failure after treatment with CASGEVY. In the clinical trials, all treated patients achieved neutrophil engraftment and no patients received rescue CD34 + cells. Monitor absolute neutrophil counts (ANC) and manage infections according to standard guidelines and medical judgement. In the event of neutrophil engraftment failure, patients should be infused with rescue CD34 + cells [see Adverse Reactions (6.1) ] . Granulocyte Colony-Stimulating Factor (G-CSF) is not recommended for 21 days after CASGEVY infusion. 5.2 Delayed Platelet Engraftment Delayed platelet engraftment has been observed with CASGEVY treatment. There is an increased risk of bleeding until platelet engraftment is achieved [see Adverse Reactions (6.1) ] . Monitor patients for bleeding according to standard guidelines and medical judgement. Conduct frequent platelet counts until platelet engraftment and platelet recovery are achieved. Perform blood cell count determination and other appropriate testing whenever clinical symptoms suggestive of bleeding arise. 5.3 Hypersensitivity Reactions Hypersensitivity reactions, including anaphylaxis, can occur due to dimethyl sulfoxide (DMSO) or dextran 40 in the cryopreservation solution. Monitor patients for hypersensitivity reactions during and after infusion. 5.4 Off-Target Genome Editing Risk The risk of unintended, off-target editing in an individual's CD34 + cells cannot be ruled out due to genetic variants. The clinical significance of potential off-target editing is unknown.
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adverse reactions
6 ADVERSE REACTIONS The most common Grade 3 or 4 non-laboratory adverse reactions (incidence ≥ 25%) were mucositis and febrile neutropenia in patients with SCD and TDT, and decreased appetite in patients with SCD. ( 6 ) The most common Grade 3 or 4 laboratory abnormalities (≥ 50%) were neutropenia, thrombocytopenia, leukopenia, anemia, and lymphopenia. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Vertex Pharmaceuticals Incorporated at 1-877-634-8789 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The most common Grade 3 or 4 non-laboratory adverse reactions (occurring in ≥ 25%) were mucositis and febrile neutropenia in patients with SCD and patients with TDT, and decreased appetite in patients with SCD. All (100%) of the patients with TDT and SCD experienced Grade 3 or 4 neutropenia and thrombocytopenia. Other common Grade 3 or 4 laboratory abnormalities (≥ 50%) include leukopenia, anemia and lymphopenia. Sickle Cell Disease The safety of CASGEVY in patients with SCD was evaluated in two open-label, single-arm trials (Trial 1 and Trial 4) and a long-term follow-up trial that included patients with SCD and TDT (Trial 3). Trial 1 included 44 patients 12 years and older and Trial 4 included 11 patients 5 years to less than 12 years of age. Patients were treated with CASGEVY after undergoing myeloablative conditioning with busulfan. Trial 1 (patients 12 years and older) The median (min, max) duration of follow-up for 44 patients with SCD after being administered CASGEVY was 19.3 (0.8, 48.1) months. Serious adverse reactions after myeloablative conditioning and CASGEVY infusion were observed in 45% of patients with SCD. The most common serious adverse reactions (≥ 2 patients) were cholelithiasis, pneumonia, abdominal pain, constipation, pyrexia, abdominal pain upper, non-cardiac chest pain, oropharyngeal pain, pain, and sepsis. One (2%) patient died due to a COVID-19 infection and subsequent respiratory failure. The event was not related to CASGEVY. Trial 4 (patients 5 years to less than 12 years of age) The median (min, max) duration of follow-up after being a...
adverse reactions table
Table 2: Grade 3 or 4 non-laboratory adverse reactions in ≥ 10% of patients with SCD who underwent busulfan myeloablative conditioning and received CASGEVY in Trial 1 with corresponding incidences in Trial 4: Day 1 to Month 24 after CASGEVY infusion Table includes adverse events associated with busulfan myeloablative conditioning and treatment with CASGEVY.System organ class, preferred termTrial 1 (N=44) n (%)Trial 4 (N=11) n (%)Blood and lymphatic system disordersFebrile neutropenia21 (48)8 (73)Gastrointestinal disordersMucositis Mucositis includes mucosal inflammation, pharyngeal inflammation, and stomatitis., Encompasses preferred terms that belong to other system organ class.38 (86)8 (73)Abdominal pain Abdominal pain includes abdominal pain and abdominal pain upper.5 (11)0Hepatobiliary disordersCholelithiasis5 (11)0Metabolism and nutrition disordersDecreased appetite18 (41)3 (27)Musculoskeletal and connective tissue disordersMusculoskeletal pain Musculoskeletal pain includes back pain, musculoskeletal chest pain, neck pain, non-cardiac chest pain, and pain in extremity., 6 (14)0Skin and subcutaneous tissue disordersPruritus5 (11)0