A Phase 3 Study to Evaluate Efficacy and Safety of a Single Dose of Exa-cel in Subjects with Severe Sickle Cell Disease, βS/βC Genotype

Prior treatment

• Prior hematopoietic stem cell transplant (HSCT).
• HbF level >15.0%, irrespective of concomitant treatment with HbF-inducing treatments such as HU.
• Any prior or current malignancy or myeloproliferative disorder or a significant immunodeficiency disorder.

Other illness

• Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the investigator.
• Subjects with history of alloimmunization to RBC antigens and for whom the investigator anticipates that there will be insufficient RBC units available for the duration of the study.
• History of any illness or any clinical condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk to the subject.
• Advanced liver disease (as defined in the protocol)

Lab values

• A willing and healthy 10/10 Human Leukocyte Antigen (HLA)-matched related donor is available per investigator’s judgement.
• White blood cell (WBC) count <3 × 109 /L or platelet count <50 × 109 /L, not related to hypersplenism per investigator judgment.

Other

• Intolerance, contraindication, or known sensitivity to plerixafor or busulfan. Subject must not have any risk factors in the opinion of the investigator that would increase the likelihood of busulfan-related toxicities.
• Pregnancy or breastfeeding

• Documented βS/βC (HbSC) genotype. Subject can be enrolled based on historical genotype results, but confirmation of genotype is required before start of busulfan conditioning.
• Subjects with severe SCD. Severe SCD is defined by the occurrence of at least 2 of the following events per year during the 2-year period before screening, while receiving appropriate supportive care: • Acute pain event that requires a visit to a medical facility and administration of pain medications or RBC transfusions • Acute chest syndrome, as indicated by the presence of a new pulmonary infiltrate associated with pneumonia-like symptoms, pain, or fever • Priapism lasting >2 hours and requiring a visit to a medical facility • Splenic sequestration, as defined by an enlarged spleen, left upper quadrant pain, and an acute decrease in Hb concentration of ≥2 g/dL.
• Karnofsky performance status of ≥80% for subjects ≥16 years of age or Lansky performance status of ≥80% for subjects <16 years of age.
• Eligible for autologous stem cell transplant as per investigator’s judgment.
• Willing to participate in either a long-term follow-up study (VX18-CTX001- 131) or registry study (if available) for a total of 15 years follow-up post-exa-cel infusion.