CASGEVY exagamglogene autotemcel 13000000 1/mL Injection, Suspension
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Other hematological agents class.
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🏭 Manufacturer & labeler
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🩺 Clinical
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🧪 Inactive Ingredients / Excipients
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
| Medicare Part B allowsASP · J3392 | No ASP payment limit on file for J3392 this quarter. | |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Casgevy 13000000 1/mLthis 51167-0290-09 | Vertex | 9 vials | — | — | FDA listed | — |
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⏳ Availability & biosimilar status
Biologics have no small-molecule generics; biosimilar competition is tracked in the FDA Purple Book.
Why the date isn’t exact: Biosimilar timing can change because patents may be challenged, settled, licensed, added or removed, and litigation can move the real date earlier or later.
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- Biologic patent
- A patent the reference product’s maker has publicly listed. A biosimilar generally can’t launch until these expire — unless they’re invalidated or resolved in a settlement.
- Reference-product exclusivity
- A flat 12 years of FDA market protection from the biologic’s first licensure (the BPCIA). No biosimilar can be licensed before it ends, regardless of patents.
- Interchangeable exclusivity
- The first interchangeable biosimilar can earn a period as the only interchangeable version (pharmacists can substitute it without the prescriber).
- Earliest biosimilar (LOE)
- The latest of all the dates above — the soonest a biosimilar can realistically reach the market. Litigation and settlements can move it earlier.
Biologics have no small-molecule “generics” — competition comes from FDA-licensed biosimilars, tracked in the FDA Purple Book.
| Code | What it grants | Expires |
|---|---|---|
| RefProduct | Reference-product exclusivity (12-year, BPCIA) — no biosimilar can be licensed before this date | Dec 8, 2035 |
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 51167-0290-09 You're viewing this | 9 VIAL in 1 CARTON (51167-290-09) / 20 mL in 1 VIAL (51167-290-01) | 2023-12-08 | Active |
🧭 About this NDC listing & data coverage
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| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | — Not published for this NDC No photo available yet for this listing. |
| Inactive ingredients (structured) | — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is available. |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | ✓ Available |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
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📄 Full FDA label FDA SPL
🎯 Indications and Usage ▾
1. INDICATIONS AND USAGE CASGEVY is indicated for the treatment of patients aged 2 years and older with: sickle cell disease (SCD) with recurrent vaso-occlusive crises transfusion-dependent β - thalassemia (TDT) CASGEVY is an autologous genome edited hematopoietic stem cell-based gene therapy indicated for the treatment of patients aged 2 years and older with: sickle cell disease (SCD) with recurrent vaso-occlusive crises (VOCs). ( 1 ) transfusion-dependent β-thalassemia (TDT).
( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION For autologous use only. For intravenous use only. Patients are required to undergo hematopoietic stem cell (HSC) mobilization followed by apheresis to obtain CD34 + cells for CASGEVY manufacturing.
( 2.2 ) Dosing of CASGEVY is based on body weight. The minimum recommended dose is 3 × 10 6 CD34 + cells/kg. ( 2.1 , 2.3 ) Full myeloablative conditioning must be administered between 48 hours and 7 days before infusion of CASGEVY.
( 2.2 ) Prophylaxis for seizures should be considered prior to initiating myeloablative conditioning. ( 2.2 ) Prophylaxis for hepatic veno-occlusive disease (VOD) should be considered prior to initiating myeloablative conditioning. ( 2.2 ) Verify that the patient's identity matches the unique patient identification information on the product labels and Lot Information Sheet prior to thaw and infusion.
( 2.2 ) Do not sample, alter, or irradiate CASGEVY. ( 2.2 ) Do not use an in-line blood filter when infusing CASGEVY. ( 2.3 ) Administer each vial of CASGEVY via intravenous infusion within 20 minutes of thaw.
( 2.3 )
2.1Dose For autologous use only. For one-time, single dose intravenous use only. The minimum recommended dose of CASGEVY is 3 × 10 6 CD34 + cells/kg. CASGEVY is provided as a single dose for infusion containing a suspension of CD34 + cells in one or more vials. See the Lot Information Sheet provided with the product shipment for additional information pertaining to the number of vials required to achieve the patient-specific dose. Administer all vials.
2.2Preparation Before CASGEVY Infusion Confirm that autologous hematopoietic stem cell (HSC) transplantation is appropriate for the patient before mobilization, apheresis and myeloablative conditioning are initiated. It is recommended that patients with SCD weigh at least 12 kg prior to start of mobilization since patients below this weight may experience difficulty in achieving the minimum target cell dose. Screen patients for HIV-1, HIV-2, HBV, HCV, and any other infectious agents in accordance with local guidelines before collection of cells for manufacturing.
CASGEVY should not be used in patients with active HIV-1, HIV-2, HBV or HCV. Discontinue disease modifying therapies (e.g., hydroxyurea, crizanlizumab) 8 weeks before the planned start of mobilization and conditioning [see Drug Interactions (7.2 , 7.3) ] . Preparation for Mobilization and Apheresis Sickle Cell Disease : Prior to planned start of mobilization, it is recommended to transfuse red blood cells (RBCs) (simple or exchange) as needed, for a minimum of 8 weeks and continue until initiation of myeloablation or reinitiate transfusion for a minimum of 8 weeks prior to start of myeloablation with a goal to maintain hemoglobin S (HbS) levels < 30% of total hemoglobin (Hb) while keeping total Hb concentration ≤ 11 g/dL.
Transfusion-dependent β thalassemia : Prior to planned start of mobilization, it is recommended to transfuse RBCs as needed, with a goal to maintain hemoglobin (Hb) ≥ 11 g/dL and continue until start of myeloablation or reinitiate transfusion for at least 60 days prior to start of myeloablation. Mobilization and Apheresis HSC mobilization followed by apheresis to isolate the CD34 + cells is required to manufacture CASGEVY. Refer to the prescribing information for the mobilization agent(s) used, prior to treatment.
See Clinical Studies (14) for description of the mobilization agents used in the clinical trials. Alternative mobilization regimens may be considered if clinically indicated. Sickle Cell Disease : Administer plerixafor 0.24 mg/kg/day via subcutaneous injection 2 to 3 hours prior to planned apheresis for a maximum of 3 days.
Do not use Granulocyte Colony-Stimulating Factor (G-CSF) for mobilization in patients with SCD. Transfusion-dependent β thalassemia : Administer G-CSF for 5 to 6 days, starting 4 days prior to plerixafor administration. In non-splenectomized patients, administer 5 μg/kg G-CSF every 12 hours intravenously or su…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS CASGEVY is a cell suspension for intravenous infusion. A single dose of CASGEVY is composed of one or more vials. Each vial contains 4 to 13 × 10 6 CD34 + cells/mL suspended in 1.5 to 20 mL cryopreservation medium [see How Supplied/Storage and Handling (16) ] .
The minimum recommended dose of CASGEVY is 3 × 10 6 CD34 + cells per kg of body weight. See the Lot Information Sheet(s) for actual strength and dose. The Lot Information Sheet is included inside the lid of each liquid nitrogen dry shipper used to transport CASGEVY.
CASGEVY is a cell suspension for intravenous infusion. ( 3 ) The minimum recommended dose of CASGEVY is 3 × 10 6 CD34 + cells per kg of body weight, which may be composed of multiple vials. ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS None. None. ( 4 )
⚠️ 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 )
5.1Neutrophil 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.
5.2Delayed 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.
5.3Hypersensitivity 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.
5.4Off-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.
🤒 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.
6.1Clinical 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 administered CASGEVY was 16.9 (7.6, 24.3) months [see Use in Specific Populations (8.4) , Clinical Pharmacology (12.3) , and Clinical Studies (14) ] . Serious adverse reactions after myeloablative conditioning and CASGEVY infusion were observed in 46% of patients with SCD. The most common serious adverse reactions (all in 1 patient each) were enterococcal sepsis, platelet count decreased, and viral abdominal infection.
Table 2 presents the Grade 3 or 4 non-laboratory adverse reactions observed after myeloablative conditioning and CASGEVY infusion in at least 10% of patients in Trial 1 with corresponding incidences for Trial 4. Table 3 presents the Grade 3 or 4 laboratory abnormalities that occurred in at least 10% of patients with SCD. 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 term Trial 1 (N=44) n (%) Trial 4 (N=11) n (%) Blood and lymphatic system disorders Febrile neutropenia 21 (48) 8 (73) Gastrointestinal disorders Mucositis 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) 0 Hepatobiliary disorders Cholelithiasis 5 (11) 0 Metabol…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS 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. Granulocyte Colony-Stimulating Factor: Granulocyte Colony-Stimulating Factor (G-CSF) must not be used for CD34 + HSC mobilization of patients with SCD.
( 7.1 ) Hydroxyurea: Discontinue hydroxyurea at least 8 weeks prior to start of mobilization and conditioning. ( 7.2 ) Crizanlizumab: Discontinue the use of crizanlizumab at least 8 weeks prior to start of mobilization and conditioning. ( 7.3 ) Iron Chelators: Discontinue iron chelators at least 7 days prior to initiation of myeloablative conditioning.
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. ( 7.4 )
7.1Use of Granulocyte Colony-Stimulating Factor (G-CSF) Granulocyte Colony - Stimulating Factor (G-CSF) must not be used for CD34 + HSC mobilization of patients with SCD [ see Warnings and Precautions (5.1) ] .
7.2Use 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.
7.3Use of Crizanlizumab Discontinue the use of crizanlizumab at least 8 weeks prior to start of mobilization and conditioning, as its interaction potential with mobilization and myeloablative conditioning agents is not known.
7.4Use 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.
7.5Live Vaccines The safety of immunization with live viral vaccines during or following CASGEVY treatment has not been studied.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Consider the risks of mobilization and myeloablative conditioning agents in patients with reproductive potential and patients that are pregnant or breastfeeding.
8.1Pregnancy Risk Summary There are no clinical data from the use of exagamglogene autotemcel during pregnancy. No animal reproductive and developmental toxicity studies have been conducted with exagamglogene autotemcel to assess whether it can cause fetal harm when administered to a pregnant patient. CASGEVY must not be administered during pregnancy because of the risks associated with myeloablative conditioning.
Pregnancy after CASGEVY infusion should be discussed with the treating physician(s). In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
8.2Lactation Risk Summary There are no data on the presence of exagamglogene autotemcel in human or animal milk, the effects on the breastfed child, or the effects on milk production. Because of the potential risks associated with myeloablative conditioning, breastfeeding should be discontinued during conditioning. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for CASGEVY and any potential adverse effects on the breastfed child from CASGEVY or from the underlying maternal condition.
Breastfeeding after CASGEVY infusion should be discussed with the treating physician(s).
8.3Females and Males of Reproductive Potential Pregnancy Testing A negative serum pregnancy test must be confirmed prior to the start of each mobilization cycle and re-confirmed prior to myeloablative conditioning. Contraception There are insufficient exposure data to provide a precise recommendation on duration of contraception following treatment with CASGEVY. Females of childbearing potential and males capable of fathering a child should use an effective method 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 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.
Infertility has been observed with myeloablative conditioning therefore, advise patients of fertility preservation options before treatment, if appropriate.
8.4Pediatric Use Sickle Cell Disease The safety and effectiveness of CASGEVY have been established in pediatric patients with SCD aged 5 years and older and are supported by 2 adequate and well-controlled clinical studies (Trials 1 and 4). Trial 1 included 12 patients aged 12 years to less than 18 years and Trial 4 included 11 patients aged 5 years to less than 12 years. The primary efficacy outcome of VF12 was 86% in patients aged 12 years to less than 18 years and 100% in patients aged 5 years to less than 12 years [see Adverse Reactions (6.1) and Clinical Studies (14.1) ] .
CASGEVY has not been studied in patients less than 5 years of age in clinical trials. The use of CASGEVY in pediatric patients aged 2 years to less than 5 years of age with SCD is supported by extrapolation of data from 2 adequate and well-controlled studies (Trials 1 and 4). The safety and efficacy of CASGEVY in pediatric patients aged less than 2 years have not been established.
Transfusion dependent β-thalassemia The safety and effectiveness of CASGEVY have been established in pediatric patients with TDT aged 5 years and older and are supported by 2 adequate and well-controlled clinical studies (Trials 2 and 5). Trial 2 included 18 patients aged 12 years to less than 18 years and Trial 5 included 15 patients aged 5 years to less than 12 years. The primary efficacy outcome of TI12 was 91% in patients aged 12 years to less than 18 years and 89% in patients aged 5 years to less than 12 years [see Adverse Reactions (6.1…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary There are no clinical data from the use of exagamglogene autotemcel during pregnancy. No animal reproductive and developmental toxicity studies have been conducted with exagamglogene autotemcel to assess whether it can cause fetal harm when administered to a pregnant patient. CASGEVY must not be administered during pregnancy because of the risks associated with myeloablative conditioning.
Pregnancy after CASGEVY infusion should be discussed with the treating physician(s). In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
🧒 Pediatric Use ▾
8.4Pediatric Use Sickle Cell Disease The safety and effectiveness of CASGEVY have been established in pediatric patients with SCD aged 5 years and older and are supported by 2 adequate and well-controlled clinical studies (Trials 1 and 4). Trial 1 included 12 patients aged 12 years to less than 18 years and Trial 4 included 11 patients aged 5 years to less than 12 years. The primary efficacy outcome of VF12 was 86% in patients aged 12 years to less than 18 years and 100% in patients aged 5 years to less than 12 years [see Adverse Reactions (6.1) and Clinical Studies (14.1) ] .
CASGEVY has not been studied in patients less than 5 years of age in clinical trials. The use of CASGEVY in pediatric patients aged 2 years to less than 5 years of age with SCD is supported by extrapolation of data from 2 adequate and well-controlled studies (Trials 1 and 4). The safety and efficacy of CASGEVY in pediatric patients aged less than 2 years have not been established.
Transfusion dependent β-thalassemia The safety and effectiveness of CASGEVY have been established in pediatric patients with TDT aged 5 years and older and are supported by 2 adequate and well-controlled clinical studies (Trials 2 and 5). Trial 2 included 18 patients aged 12 years to less than 18 years and Trial 5 included 15 patients aged 5 years to less than 12 years. The primary efficacy outcome of TI12 was 91% in patients aged 12 years to less than 18 years and 89% in patients aged 5 years to less than 12 years [see Adverse Reactions (6.1) and Clinical Studies (14.2) ] .
CASGEVY has not been studied in patients less than 5 years of age in clinical trials. The use of CASGEVY in pediatric patients 2 years to less than 5 years of age with TDT is supported by extrapolation of data from 2 adequate and well-controlled studies (Trials 2 and 5). The safety and efficacy of CASGEVY in pediatric patients aged less than 2 years have not been established.
🧓 Geriatric Use ▾
8.5Geriatric Use CASGEVY has not been studied in patients > 65 years of age. Autologous HSC transplantation must be appropriate for a patient to be treated with CASGEVY.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action After CASGEVY infusion, the edited CD34 + cells engraft in the bone marrow and differentiate to erythroid lineage cells with reduced BCL11A expression. Reduced BCL11A expression results in an increase in γ-globin expression and HbF protein production in erythroid cells. In patients with severe sickle cell disease, HbF expression reduces intracellular hemoglobin S (HbS) concentration, preventing the red blood cells from sickling and addressing the underlying cause of disease, thereby eliminating VOCs.
In patients with transfusion-dependent β-thalassemia, γ-globin production improves the α-globin to non-α-globin imbalance thereby reducing ineffective erythropoiesis and hemolysis and increasing total hemoglobin levels, addressing the underlying cause of disease, and eliminating the dependence on regular red blood cell (RBC) transfusions.
12.2Pharmacodynamics Sickle Cell Disease Fetal Hemoglobin and Total Hemoglobin Trial 1 (patients 12 years and older) HbF and total Hb over time are provided in Table 10 for all patients administered CASGEVY in Trial 1 for the treatment of sickle cell disease (full analysis set). HbF and total Hb over time for the subset of patients included in the primary efficacy analysis were consistent with full analysis set. Table 10: Proportion of hemoglobin comprised by HbF (%) and total Hb (g/dL) over time in patients with SCD in Trial 1 CASGEVY Full Analysis Set (FAS) (N=44) Proportion of total Hb comprised by HbF (%) %HbF/Hb data not available for all patients at all timepoints.
SD: Standard Deviation. Total Hb (g/dL) Month 3 n 43 43 Mean (SD) 36.9 (9.0) 11.9 (1.5) Median (min, max) 36.2 (17.8, 59.6) 11.9 (8.2, 15.4) Month 6 n 38 38 Mean (SD) 43.9 (8.6) 12.5 (1.8) Median (min, max) 44.3 (14.9, 68.4) 12.3 (7.2, 15.9) Month 12 n 32 31 Mean (SD) 43.4 (4.6) 13.0 (1.5) Median (min, max) 42.9 (35.1, 52.1) 12.9 (10.3, 15.7) Month 18 n 27 27 Mean (SD) 42.3 (5.8) 13.3 (1.9) Median (min, max) 43.1 (27.5, 53.3) 12.7 (11.0, 17.3) Month 24 n 17 17 Mean (SD) 42.1 (5.2) 13.1 (1.8) Median (min, max) 42.2 (33.3, 49.1) 13.0 (10.5, 17.3) The mean (SD) proportion of Hb comprised by HbF was 43.9% (8.6%) at Month 6 and was maintained thereafter.
Increases in mean (SD) total Hb levels were observed as early as Month 3 after CASGEVY infusion, continued to increase to 12.5 (1.8) g/dL at Month 6, and was maintained thereafter. Of the 44 patients infused with CASGEVY, three male patients reached total Hb levels of at least 16.5 g/dL at one or more time points after Month 9. Consistent with the increase in HbF levels, the mean (SD) proportion of circulating erythrocytes expressing HbF (F-cells) at Month 3 was 70.1% (13.8%) and continued to increase over time to 94.0% (12.4%) at Month 6, with levels remaining stable thereafter, indicating sustained pan-cellular expression of HbF.
Trial 4 (patients 5 years to less than 12 years of age) Of the 11 patients with SCD treated with CASGEVY in Trial 4, the median (min, max) duration of follow up after infusions was 16.9 (7.6, 24.3) months. Increases in mean (SD) total Hb and HbF levels were observed by Month 3 after CASGEVY infusion. Mean total Hb (SD) continued to increase to 12.2 (1.4) g/dL at Month 6 and was maintained at normal values for age (≥ 11.5 g/dL) through the duration of follow-up.
The mean (SD) proportion of Hb comprised by HbF was 49.5% (6.4%) at Month 6 and was maintained at ≥ 40% through the duration of follow-up. Consistent with the increase in HbF levels, the mean (SD) proportion of circulating erythrocytes expressing HbF (F-cells) at Month 6 was 98.8% (0.9%) with levels remaining stable through the duration of follow-up, indicating sustained pan-cellular expression of HbF. Proportion of Alleles with Intended Genetic Modification Trial 1 (patients 12 years and older) The mean (SD) proportion of alleles with intended genetic modification in the bone marrow and in peripheral blood is shown in Table 11 for all patients admin…
🧬 Mechanism of Action ▾
12.1Mechanism of Action After CASGEVY infusion, the edited CD34 + cells engraft in the bone marrow and differentiate to erythroid lineage cells with reduced BCL11A expression. Reduced BCL11A expression results in an increase in γ-globin expression and HbF protein production in erythroid cells. In patients with severe sickle cell disease, HbF expression reduces intracellular hemoglobin S (HbS) concentration, preventing the red blood cells from sickling and addressing the underlying cause of disease, thereby eliminating VOCs.
In patients with transfusion-dependent β-thalassemia, γ-globin production improves the α-globin to non-α-globin imbalance thereby reducing ineffective erythropoiesis and hemolysis and increasing total hemoglobin levels, addressing the underlying cause of disease, and eliminating the dependence on regular red blood cell (RBC) transfusions.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING CASGEVY is supplied in one or more vials containing a frozen suspension of genome edited autologous CD34 + cells in a cryopreservation medium containing 5% DMSO and dextran 40. CASGEVY is stored in the vapor phase of liquid nitrogen and is shipped from the manufacturing facility to the treatment center storage facility in one or more cryoshipper(s). CASGEVY is supplied in vial(s) packaged in carton(s).
One carton contains a single lot of CASGEVY consisting of 1 to 9 vials. A single dose of CASGEVY may consist of multiple CASGEVY lots, and therefore may consist of multiple cartons. A Lot Information Sheet listing the total dose of CASGEVY is affixed inside each shipper.
NDC 51167-290-09 Match the identity of the patient with the patient identifiers on each carton, vial, and Lot Information Sheet upon receipt. Store the vial(s) in the vapor phase of liquid nitrogen at ≤ -135 °C (≤ -211 °F) until ready for thaw and administration. Thaw CASGEVY prior to administration.
Thaw and infuse one vial of CASGEVY at a time [see Dosage and Administration (2.2 , 2.3) ] . Once thawed, CASGEVY must be administered within 20 minutes [see Dosage and Administration (2.2 , 2.3) ] . Do not re-freeze CASGEVY after thawing.
Do not irradiate CASGEVY.
📦 Storage and Handling ▾
NDC 51167-290-09 Match the identity of the patient with the patient identifiers on each carton, vial, and Lot Information Sheet upon receipt. Store the vial(s) in the vapor phase of liquid nitrogen at ≤ -135 °C (≤ -211 °F) until ready for thaw and administration. Thaw CASGEVY prior to administration.
Thaw and infuse one vial of CASGEVY at a time [see Dosage and Administration (2.2 , 2.3) ] . Once thawed, CASGEVY must be administered within 20 minutes [see Dosage and Administration (2.2 , 2.3) ] . Do not re-freeze CASGEVY after thawing.
Do not irradiate CASGEVY.
📋 Description ▾
11 DESCRIPTION CASGEVY (exagamglogene autotemcel) is a cellular gene therapy consisting of autologous CD34 + HSCs edited by CRISPR/Cas9-technology at the erythroid specific enhancer region of the BCL11A gene to reduce BCL11A expression in erythroid lineage cells, leading to increased fetal hemoglobin (HbF) protein production. CASGEVY is prepared from the patient's own HSCs, which are obtained via apheresis procedure(s). The autologous cells are enriched for CD34 + cells, and then genome edited ex vivo by introducing the CRISPR/Cas9 ribonucleoprotein (RNP) complex by electroporation.
The guide RNA included in the RNP complex enables CRISPR/Cas9 to make a precise DNA double-strand break at a critical transcription factor binding site (GATA1) in the erythroid specific enhancer region of the BCL11A gene. As a result of the editing, GATA1 binding is disrupted and BCL11A expression is reduced. This reduction in BCL11A expression conversely results in an increase in gamma-globin expression and downstream fetal hemoglobin formation.
The edited CD34 + cells are formulated into a suspension in a sterile cryopreservation medium and cryopreserved. CASGEVY is shipped as a frozen suspension in patient-specific vial(s). The product is thawed prior to infusion and administered as an autologous HSC transplant [see Dosage and Administration (2.2) and How Supplied/Storage and Handling (16) ] .
Due to the presence of cells, the thawed product may be clear to slightly cloudy and may contain small inherent proteinaceous particles or visible cell aggregates. The formulation contains 5% dimethyl sulfoxide (DMSO) and dextran 40.
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient or caregiver to read the FDA-approved patient labeling (Patient Information). Prior to treatment, advise patients or caregivers of the following: Risks of mobilization and conditioning agents - Advise patients of the risks associated with mobilization and myeloablative conditioning agents and to read the FDA-approved patient labeling (Patient Information) for these agents. Potential need for additional cell collection - Ensure patients understand that if the minimum dose of CASGEVY is not met after initial product manufacturing, additional cycles of mobilization and apheresis will be needed to collect additional cells for product manufacture [see Dosage and Administration (2.2) ] .
Concomitant medications - Advise patients of the need to avoid the following medications: Disease modifying therapies (e.g., hydroxyurea, crizanlizumab) should be discontinued 8 weeks before the planned start of mobilization and conditioning [see Drug Interactions (7.2 , 7.3) ] . Iron chelation should be stopped at least 7 days prior to myeloablative conditioning. If iron chelation is required, the use of non-myelosuppressive iron chelators should be avoided for at least 3 months after CASGEVY administration and use of myelosuppressive iron chelators should be avoided for at least 6 months after CASGEVY administration.
Phlebotomy can be used in lieu of iron chelation, when appropriate [see Drug Interactions (7.4) ] . After treatment, advise patients or caregivers of the following: Risk of neutrophil engraftment failure - Advise patients they will need to receive rescue treatment with their collection of unmodified CD34 + cells if they do not achieve neutrophil engraftment after CASGEVY administration [see Dosage and Administration (2.3) and Warnings and Precautions (5.1) ] . Risk of bleeding - There is an increased risk of bleeding from initiation of myeloablative conditioning until platelet engraftment is achieved.
Advise patients to monitor for signs and symptoms of new or worsening bleeding or bruising and have frequent blood draws for platelet counts, until platelet recovery has been achieved [see Warnings and Precautions (5.2) ] . Donation of blood products - Advise patients that they should not donate blood, organs, tissues, or cells at any time in the future.