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Exa-cel

Phase 2

Sickle Cell Disease | Cell therapy | Hematology |Vertex Pharmaceuticals Incorporated|Last Updated: Sep 16, 2026

Success Probability

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Trial Design

UNCONTROLLEDDMC
Total Trials1
Total Enrollment63

FDA Designations

PRIORITY_REVIEW

Clinical trial landscape

Exa-cel · 1 trial · 3 indications

Phase 2 1
NCT03745287A Safety and Efficacy Study Evaluating CTX001 in Subjects With Severe Sickle Cell DiseaseSickle Cell Disease
COMPLETED63 Analytics
PHASE2COMPLETED
A Safety and Efficacy Study Evaluating CTX001 in Subjects With Severe Sickle Cell Disease
Sickle Cell DiseaseUnlock trial analytics

Study Endpoints

Primary Endpoints

Percentage of Participants Who Have Not Experienced Any Severe Vaso-occlusive Crisis (VOC) for at Least 12 Consecutive Months (VF12) After Exa-cel Infusion
From 60 days after last RBC transfusion up to 2 years after exa-cel infusion

A VOC is a condition of SCD characterized by vaso-occlusion presenting as recurrent pain episodes. The percentage of participants who remain VOC free after achieving VF12 were data reported in the outcome measure.

Percentage of Participants Who Achieve Neutrophil Engraftment
Up to 24 months post exa-cel infusion.

Neutrophil engraftment is defined as the first day of 3 consecutive measurements of absolute neutrophil count (ANC)≥500/μL on 3 different days, within 42 days after exa-cel infusion without the use of unmodified CD34+ cells after reaching the nadir, defined as ANC \<500/µL.

Time to Neutrophil Engraftment for Participants Who Achieve Neutrophil Engraftment
Up to 24 months post exa-cel infusion.

Neutrophil engraftment is defined as the first day of 3 consecutive measurements of absolute neutrophil count (ANC)≥500/μL on 3 different days, without use of the unmodified CD34+ cells after reaching the nadir, defined as ANC\<500/μL. Time to neutrophil engraftment was calculated by the neutrophil engraftment date subtract exa-cel infusion date +1.

Time to Platelet Engraftment for Participants Who Achieve Platelet Engraftment
From Exa-cel infusion up to 2 years after exa-cel infusion

Platelet engraftment is defined as the first day of 3 consecutive measurements of unsupported (no platelet transfusions for the last 7 days) platelet ≥50,000/μL on 3 different days after Exa-cel infusion. For participants discharged early day 7 after the last platelet transfusion will be the day of platelet engraftment, as long as 3 subsequent and consecutive unsupported measurements on 3 different days are \>50,000/μL. For participants who have been discharged prior to platelet engraftment, it is recommended to collect blood every 2 to 3 days to obtain an accurate assessment of platelet engraftment. Time to platelet engraftment was defined as first of 3 consecutive measurements on 3 different days with platelet ≥50 × 109/L without a platelet transfusion for 7 consecutive days.

Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
From receiving exa-cel infusion up to 2 years
Transplant-related Mortality (TRM) Within 100 Days After Exa-cel Infusion
Within 100 days after exa-cel infusion

The transplant-related mortality is defined as death related to Busulfan and/or exa-cel infusion. The number and proportion of TRM participants who have died within 100 days, or with at least 100 days post exa-cel infusion.

Transplant-related Mortality Within 12 Months Post Exa-cel Infusion
Within 12 months post exa-cel infusion

The transplant-related mortality is defined as death related to Busulfan and/or exa-cel infusion. The number and proportion of TRM within 12 months will be summarized for participants who have died within 12 months, or with at least 12 months post exa-cel infusion.

All-cause Mortality
From exa-cel infusion up to 2 years

All-cause mortality from exa-cel infusion up to 2 years

Secondary Endpoints

Percentage of Participants Free From Inpatient Hospitalization for Severe VOCs Sustained for at Least 12 Months (HF12)
From 60 days after last RBC transfusion up to 2 years after exa-cel infusion
Relative Reduction From Baseline in Annualized Rate of Severe VOCs for Participants Who do Not Achieve VF12 up to 24 Months After Exa-cel Infusion
From 60 days after last RBC transfusion up to 2 years after exa-cel infusion
Percentage of Participants With at Least 90% Relative Reduction From Baseline in Annualized Rate of Severe VOCs for Participants Who do Not Achieve VF12 up to 24 Months After Exa-cel Infusion
From 60 days after last RBC transfusion up to 2 years after exa-cel infusion
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Study Design & Arms

AllocationNA
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Exa-celEXPERIMENTALExa-cel (autologous CD34+ hHSPCs modified with CRISPR-Cas9 at the erythroid lineage-specific enhancer of the BCL11A gene). Participants received a single infusion of exa-cel through a central venous catheter on Day 1.

Interventions

NameTypeDescription
Exa-celBIOLOGICALAdministered by IV infusion following myeloablative conditioning with busulfan.
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Eligibility Criteria

Age Range12 Years to 35 Years
SexALL
Healthy VolunteersNo
Study Sites17

Key Inclusion Criteria: * Diagnosis of severe sickle cell disease as defined by: * Documented severe sickle cell disease genotype * History of at least two severe vaso-occlusive crisis events per year for the previous two years prior to enrollment * Eligible for autologous stem cell transplant as p...

Countries:United StatesBelgiumCanadaFranceGermanyItalyUnited Kingdom
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