Evaluation of Efficacy and Safety of a Single Dose of CTX001 in Participants With Transfusion-Dependent β-Thalassemia and Severe Sickle Cell Disease

• CTX001 (Biological), also known as Exagamglogene autotemcel, Exa-cel: Administered by intravenous (IV) infusion following myeloablative conditioning with busulfan

Primary outcomes

• Fetal Hemoglobin (HbF) Concentration Over Time [Up to 12 Months After CTX001 Infusion]
• Total Hemoglobin (Hb) Concentration Over Time [Up to 12 Months After CTX001 Infusion]

Secondary outcomes

• TDT and SCD: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [From Signing of Informed Consent up to 12 Months After CTX001 Infusion]
• TDT and SCD: Proportion of Participants With Engraftment (First day of 3 Consecutive Measurements of Absolute Neutrophil Count (ANC) >=500 per Microliter [mcgL] on 3 Different Days) [Within 42 Days After CTX001 Infusion]
• TDT and SCD: Time to Engraftment [Up to 12 Months After CTX001 Infusion]
• TDT and SCD: Incidence of Transplant-Related Mortality (TRM) Within 100 Days After CTX001 Infusion [Within 100 Days After CTX001 Infusion]
• TDT and SCD: Incidence of TRM Within 12 Months After CTX001 Infusion [Within 12 Months After CTX001 Infusion]
• TDT and SCD: Incidence of All-cause Mortality [From Signing of Informed Consent up to 12 Months After CTX001 Infusion]
• TDT and SCD: Relative Reduction in Annualized Volume of RBC Transfusions [From Day 60 up to 12 Months After CTX001 Infusion]
• TDT and SCD: Proportion of Alleles With Intended Genetic Modification Present in Peripheral Blood Over Time [Up to 12 Months After CTX001 Infusion]
• TDT and SCD: Proportion of Alleles With Intended Genetic Modification Present in CD34+ Cells of the Bone Marrow Over Time [Up to 12 Months After CTX001 Infusion]
• TDT: Duration Transfusion Free in Participants [Up to 12 Months After CTX001 Infusion]
• SCD: Relative Reduction in Annualized Rate of Severe Vaso-Occlusive Crises (VOCs) [From Baseline up to 12 Months After CTX001 Infusion]
• SCD: Relative Reduction in Annualized Rate of Inpatient Hospitalizations for Severe VOCs [From Baseline up to 12 Months After CTX001 Infusion]
• SCD: Relative Reduction in Annualized Duration of Hospitalization for Severe VOCs [From Baseline up to 12 Months After CTX001 Infusion]
• SCD: Relative Reduction in Haptoglobin [From Baseline up to 12 Months After CTX001 Infusion]
• SCD: Relative Reduction in Lactate dehydrogenase [From Baseline up to 12 Months After CTX001 Infusion]
• SCD: Relative Reduction in Total Bilirubin [From Baseline up to 12 Months After CTX001 Infusion]
• SCD: Relative Reduction in Indirect Bilirubin [From Baseline up to 12 Months After CTX001 Infusion]

Sex: All, ages: 12 Years to 35 Years

Key Inclusion Criteria:

* Participants with TDT and SCD:
* Eligible for autologous stem cell transplant as per investigator's judgment.
* Participants with TDT:
* Diagnosis of TDT as defined by:
* Documented homozygous β-thalassemia or compound heterozygous β-thalassemia including β-thalassemia/hemoglobin E (HbE). Participants can be enrolled based on historical data, but a confirmation of the genotype using the study central laboratory will be required before busulfan conditioning
* History of at least 100 milliliter (mL)/kilograms (kg)/year or 10 units/year of packed red blood cells (RBC) transfusions in the prior 2 years before signing the consent or the last rescreening for patients going through re-screening
* Participants with SCD:
* Diagnosis of severe SCD as defined by:
* Documented SCD genotypes
* History of at least two severe VOCs events per year for the previous two years prior to enrollment

Key Exclusion Criteria:

* Participants with TDT and SCD:
* A willing and healthy 10/10 human leukocyte antigen (HLA)-matched related donor is available per investigator's judgement
* Prior hematopoietic stem cell transplant (HSCT)
* Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the investigator
* Participants with TDT:
* Participants with associated α-thalassemia and >1 alpha deletion, or alpha multiplications
* Participants with sickle cell β-thalassemia variant
* Participants with SCD:
* History of untreated moyamoya syndrome or presence of moyamoya syndrome at screening

Other protocol defined Inclusion/Exclusion criteria may apply.