CASGEVY is indicated for the treatment of patients aged 12 years and older with sickle cell disease (SCD) with recurrent vaso-occlusive crises (VOCs)1
Identifying potential candidates with SCD for CASGEVY:
Age Consideration:
Is my patient at least 12 years of age?
Treatment Challenges:
How often is my patient experiencing VOCs or hospital stays on their current treatment?
Has my patient shown interest in exploring new treatments or gene-therapy options?
Support Assessment:
How equipped is my patient with a supportive network to navigate their treatment journey effectively?
Physical Condition:
Is my patient able to tolerate a stem cell transplant?
Is my patient at a suitable stage in their life to embark on the treatment journey with CASGEVY?
Does my patient have plans to start a family in the future?
*Infertility has been observed with myeloablative conditioning therefore, advise patients of fertility preservation options before treatment, if appropriate.1
By considering these factors, healthcare providers can collaborate with their patients to tailor treatment approaches effectively.
By considering these factors, healthcare providers can collaborate with their patients to tailor treatment approaches effectively.
Potential candidates for CASGEVY
These are hypothetical profiles and medical providers should make their own independent decisions regarding the treatment decisions for their patients.
Meet Colin, a sports-oriented 13-year-old with SCD who loves playing basketball with his friends
- Diagnosed at birth (βS/βS genotype); discontinuation of prior therapies due to inadequate response
- Growing increasingly discouraged after missing multiple days of school and basketball practice
- Following discontinuation of other therapies, parents concerned about symptom progression
Colin’s last 24 months with SCD
Colin’s last 24 months with SCD
Colin’s selected lab values
(At last visit; values have fluctuated over the last year)
Selected lab values
- Reticulocyte count (%): 5.4 | Reference range: 0.5-1.5
- Haptoglobin (mg/dL): Below detectable limit | Reference range: 83-267
- Total hemoglobin (g/dL): 11.5 | Reference range: M: 14-18
- LDH (U/L): 416 | Reference range: 80-225
- Total bilirubin (mg/dL): 2.7 | Reference range: 0.3-1.0
- AST (U/L): 35 | Reference range: 10-40
- Creatinine (mg/dL): 0.39 | Reference range: M: 0.70-1.30
Radiology
- TCD TAMMV (cm/s): <170 | Reference range: ≤170
Meet Gladys, a 22-year-old paralegal and mother of 1 child, exhausted with her SCD and persistent and unpredictable VOCs
- Diagnosed at birth (βS/βS genotype)
- Good adherence to medications, doctor’s appointments, and wellness efforts
- Growing concerns about missing multiple days of work due to her VOCs and not being able to be there for her family
Gladys’ last 24 months with SCD
Gladys’ last 24 months with SCD
Gladys’ selected lab values
(At last visit; values have fluctuated over the last year)
Selected lab values
- Reticulocyte count (%): 5.1 | Reference range: 0.5-1.5
- Haptoglobin (mg/dL): <8 | Reference range: 83-267
- Total hemoglobin (g/dL): 9.9 | Reference range: F: 12-16
- LDH (U/L): 307 | Reference range: 80-225
- Total bilirubin (mg/dL): 2.1 | Reference range: 0.3-1.0
- AST (U/L): 66 | Reference range: 10-40
- Creatinine (mg/dL): 0.45 | Reference range: F: 0.50-1.10
ACS=acute chest syndrome; AST=aspartate aminotransferase; ED=emergency department; F=female; LDH=lactate dehydrogenase; M=male; RBC=red blood cell; SCD=sickle cell disease; TCD TAMMV=transcranial Doppler timed average mean maximum velocity; VOC=vaso-occlusive crisis.
WARNINGS AND PRECAUTIONS
Neutrophil Engraftment Failure
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.
Delayed Platelet Engraftment
Delayed platelet engraftment has been observed with CASGEVY treatment. There is an increased risk of bleeding until platelet engraftment is achieved. In the clinical trials, there was no association observed between incidence of bleeding events and time to platelet engraftment.
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.
Hypersensitivity Reactions
Hypersensitivity reactions, including anaphylaxis can occur due to dimethyl sulfoxide (DMSO) or dextran 40 in the cryopreservative solution. Monitor patients for hypersensitivity reactions during and after infusion.
Off-Target Genome Editing Risk
Although off-target genome editing was not observed in the edited CD34+ cells evaluated from healthy donors and patients, 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.
ADVERSE REACTIONS
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.
DRUG INTERACTIONS
No formal drug interaction studies have been performed. CASGEVY is not expected to interact with the hepatic cytochrome P450 family of enzymes or drug transporters.
Use of Granulocyte-Colony Stimulating Factor (G-CSF): G-CSF must not be used for CD34+ HSC mobilization of patients with SCD.
Use of Hydroxyurea: Discontinue the use of hydroxyurea at least 8 weeks prior to start of each mobilization cycle and conditioning. There is no experience of the use of hydroxyurea after CASGEVY infusion.
Use of Voxelotor and Crizanlizumab: Discontinue the use of voxelotor and crizanlizumab at least 8 weeks prior to start of mobilization and conditioning, as their interaction potential with mobilization and myeloablative conditioning agents is not known.
Use of Iron Chelators: Discontinue the use of iron chelators at least 7 days prior to initiation of myeloablative conditioning, due to potential interaction with the conditioning agent. Some iron chelators are myelosuppressive. If iron chelation is required, 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.
USE IN SPECIFIC POPULATIONS
Pregnancy/Lactation: CASGEVY must not be administered during pregnancy and breastfeeding should be discontinued during conditioning because of the risks associated with myeloablative conditioning. Pregnancy and breastfeeding after CASGEVY infusion should be discussed with the treating physician.
Females and Males of Reproductive Potential: A negative serum pregnancy test must be confirmed prior to the start of each mobilization cycle and reconfirmed prior to myeloablative conditioning.
Women of childbearing potential and men capable of fathering a child should use effective methods of contraception from start of mobilization through at least 6 months after administration of CASGEVY. Advise patients of the risks associated with conditioning agents.
Infertility has been observed with myeloablative conditioning therefore, advise patients of fertility preservation options before treatment, if appropriate.
Please see full Prescribing Information for CASGEVY.
Reference: 1. CASGEVY [prescribing information]. Vertex Pharmaceuticals Incorporated. Boston, MA; January 2024.
