Trial Outcomes & Findings for A Study Evaluating the Safety and Efficacy of Lovo-cel in Severe Sickle Cell Disease (NCT NCT02140554)

Last Updated: 2025-03-14

Results Overview

VOE-CR was defined as complete resolution of adjudicated VOEs between 6 months and 18 months post lovo-cel infusion. All reported VOEs were also adjudicated by an independent Event Adjudication Committee for purposes of endpoint analysis. VOEs were determined by adjudication committee after referring to protocol VOE. The committee was responsible for VOE assessment and determining whether an event met criteria for a VOE for all reported events.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

54 participants

Primary outcome timeframe

From 6 months to 18 months post lovo-cel infusion

Results posted on

2025-03-14

Participant Flow

A total of 54 participants-initiated stem cell collection and included in Intent-to-Treat (ITT) population, and of those 45 participants treated with lovo-cel and included in the transplant population.

Participants were enrolled as Groups A, B (B1 and B2) and C (see Reporting Groups). Since B1 and B2 contained only 2 participants and due to other factors (eg, logistical considerations), results for B1 and B2 are reported as "Group B" throughout this summary.

Participant milestones

Participant milestones
Measure	Group A Participants who had rescue cells that were collected by bone marrow harvest method and had received treatment with lovo-cel which consists of autologous CD34+ hematopoietic stem cells (HSCs) and progenitor stem cells (PSCs) (collectively referred to as hematopoietic stem and progenitor cells or HSPCs) collected from patients with sickle cell disease (SCD) by bone marrow harvest transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene (the original drug product manufacturing process for this study).	Group B Group B included only 2 participants treated with drug product cells collected differently and with drug product manufactured using different processes (one participant in Group B1 and one participant in Group B2 as detailed below). Note that, due to the small size of Groups B1 and B2 and due to other factors (including logistical considerations), these intermediate groups are combined as "Group B" throughout this summary for results reporting purposes. Group B1 participant had rescue cells and drug product cells that were collected by bone marrow harvest method and drug product was manufactured with autologous CD34+ HSPCs collected by bone marrow harvest transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene. This participant's drug product was produced in 2 lots each using two different manufacturing processes (the original drug product manufacturing process and a refined drug product manufacturing process). Group B2 Plerixafor mobilization and apheresis were used for collection of rescue cells and exploratory manufacturing development. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by bone marrow harvest transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene (using only the refined drug product manufacturing process).	Group C Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
Overall Study STARTED	9	2	43
Overall Study Transplant Population (TP)	7	2	36
Overall Study Transplant Population for VOE (TPVOE)	6	2	32
Overall Study COMPLETED	7	2	35
Overall Study NOT COMPLETED	2	0	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Group A Participants who had rescue cells that were collected by bone marrow harvest method and had received treatment with lovo-cel which consists of autologous CD34+ hematopoietic stem cells (HSCs) and progenitor stem cells (PSCs) (collectively referred to as hematopoietic stem and progenitor cells or HSPCs) collected from patients with sickle cell disease (SCD) by bone marrow harvest transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene (the original drug product manufacturing process for this study).	Group C Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
Overall Study Withdrawal of consent	1	4
Overall Study Physician Decision	1	2
Overall Study Death	0	1
Overall Study Discontinued due to failure to mobilize	0	1

Baseline Characteristics

A Study Evaluating the Safety and Efficacy of Lovo-cel in Severe Sickle Cell Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group A n=9 Participants Participants who had rescue cells that were collected by bone marrow harvest method and had received treatment with lovo-cel which consists of autologous CD34+ hematopoietic stem cells (HSCs) and progenitor stem cells (PSCs) (collectively referred to as hematopoietic stem and progenitor cells or HSPCs) collected from patients with sickle cell disease (SCD) by bone marrow harvest transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene (the original drug product manufacturing process for this study).	Group B n=2 Participants Group B included only 2 participants treated with drug product cells collected differently and with drug product manufactured using different processes (one participant in Group B1 and one participant in Group B2 as detailed below). Note that, due to the small size of Groups B1 and B2 and due to other factors (including logistical considerations), these intermediate groups are combined as "Group B" throughout this summary for results reporting purposes. Group B1 participant had rescue cells and drug product cells that were collected by bone marrow harvest method and drug product was manufactured with autologous CD34+ HSPCs collected by bone marrow harvest transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene. This participant's drug product was produced in 2 lots each using two different manufacturing processes (the original drug product manufacturing process and a refined drug product manufacturing process). Group B2 Plerixafor mobilization and apheresis were used for collection of rescue cells and exploratory manufacturing development. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by bone marrow harvest transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene (using only the refined drug product manufacturing process).	Group C n=43 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.	Total n=54 Participants Total of all reporting groups
Age, Continuous	26.0 years n=5 Participants	24.5 years n=7 Participants	24.0 years n=5 Participants	25.0 years n=4 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	0 Participants n=7 Participants	18 Participants n=5 Participants	20 Participants n=4 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	2 Participants n=7 Participants	25 Participants n=5 Participants	34 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants	2 Participants n=7 Participants	39 Participants n=5 Participants	50 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	8 Participants n=5 Participants	1 Participants n=7 Participants	39 Participants n=5 Participants	48 Participants n=4 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	4 Participants n=4 Participants

PRIMARY outcome

Timeframe: From 6 months to 18 months post lovo-cel infusion

Population: TPVOE was subset of TP participants who had at least 4 protocol VOEs in the 24 months prior to Informed Consent.TP included participants who received lovo-cel. As per planned analysis in SAP, data was analyzed and reported for Group C participants. Analysis of efficacy endpoint for Group C was planned to be reported based on the adjudicated vaso-occlusive events (VOEs).

Outcome measures

Outcome measures
Measure	Group C n=32 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
Percentage of Group C Participants Who Achieved Complete Resolution of Vaso-occlusive Events (VOE-CR)	87.5 percentage of participants Interval 71.0 to 96.5

SECONDARY outcome

Timeframe: From 6 months to 18 months post lovo-cel infusion

sVOE-CR was defined as the complete resolution of sVOEs, in the 6 to 18 months post lovo-cel infusion. All reported VOEs (including sVOEs) were adjudicated by an independent Event Adjudication Committee for purposes of endpoint analysis (referred to as Adjudicated sVOEs). sVOE were determined by adjudication committee after referring to protocol definition of sVOE. The committee was responsible for VOE assessment and determining whether an event met criteria for an sVOE for all reported events.

Outcome measures

Outcome measures
Measure	Group C n=32 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
Percentage of Group C Participants With Complete Resolution of Severe VOEs (sVOE-CR)	93.8 percentage of participants Interval 79.2 to 99.2

SECONDARY outcome

Timeframe: From at least 60 days after last pRBC transfusion up to Month 24 post lovo-cel infusion

Population: TP included participants who received lovo-cel. As per planned analysis, data was analyzed and reported only for TP Group C participants.

Globin Response is defined as meeting the following criteria for a continuous period of at least 6 months post lovo-cel infusion (starting at least 60 days after last packed red blood cell \[pRBC\] transfusion): 1. Weighted average HbAT87Q percentage of non-transfused total Hb \>=30% AND 2. Weighted average non-transfused total Hb increase of \>=3 g/dL compared to baseline total Hb OR weighted average non-transfused total Hb \>=10 g/dL

Outcome measures

Outcome measures
Measure	Group C n=36 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
Percentage of Group C Participants Who Achieved Globin Response	86.1 percentage of participants Interval 70.5 to 95.3

SECONDARY outcome

Timeframe: From first date of Globin Response to Month 24 post lovo-cel infusion

Population: TP included participants who received lovo-cel. As per planned analysis, data was analyzed and reported only for TP Group C participants. Here, "Overall number of participants analyzed" signifies TP Group C participants who achieved Globin Response.

Globin Response at Month 24 was defined as continuously meeting the following criteria from the first date of globin response initiating to Month 24 assessment post lovo-cel infusion: 1. Weighted average HbAT87Q percentage of non-transfused total Hb \>=30% AND 2. Weighted average non-transfused total Hb increase of \>=3 g/dL compared to baseline total Hb OR weighted average non-transfused total Hb \>=10 g/dL

Outcome measures

Outcome measures
Measure	Group C n=31 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
Percentage of Group C Participants Who Meet the Definition of Globin Response at Month 24	96.8 percentage of participants Interval 83.3 to 99.9

SECONDARY outcome

Timeframe: From first date of Globin Response to Month 24 post lovo-cel infusion

Duration of Globin Response is the time period from the first date of Globin Response initiating to the date of last high pressure liquid chromatography (HPLC) assessment such that the weighted average HbAT87Q (%) in non-transfused total Hb and non-transfused total Hb continuously meet Globin Response criteria. 1. Weighted average HbAT87Q percentage of non-transfused total Hb \>=30% AND 2. Weighted average non-transfused total Hb increase of \>=3 g/dL compared to baseline total Hb OR weighted average non-transfused total Hb \>=10 g/dL

Outcome measures

Outcome measures
Measure	Group C n=31 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
Duration of Globin Response in Group C Participants	20.47 months Interval 14.7 to 23.5

SECONDARY outcome

Timeframe: From Baseline up to 24 months post lovo-cel infusion

Change from baseline in the annualized number of VOEs was assessed from 24 months post lovo-cel infusion compared to the 24 months prior to Informed Consent. All reported VOEs were also adjudicated by an independent event adjudication committee for purposes of outcome analysis. VOEs were determined by adjudication committee after referring to protocol definition of VOE. The committee was responsible for VOE assessment and determining whether an event met criteria for a VOE for all reported events.

Outcome measures

Outcome measures
Measure	Group C n=32 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
Change From Baseline in the Annualized Number of VOEs in Group C Participants	-3.50 Number of VOEs/year Interval -14.6 to -1.1

SECONDARY outcome

Timeframe: From Baseline up to 24 months post lovo-cel infusion

Change from baseline in the annualized number of sVOEs was assessed from 24 months post lovo-cel infusion compared to the 24 months prior to Informed Consent. All reported VOEs (including sVOEs) were adjudicated by an independent Event Adjudication Committee for purposes of endpoint analysis. sVOE were determined by adjudication committee after referring to protocol definition of sVOE. The committee was responsible for VOE assessment and determining whether an event met criteria for an sVOE for all reported events.

Outcome measures

Outcome measures
Measure	Group C n=32 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
Change From Baseline in the Annualized Number of sVOEs in Group C Participants	-3.00 Number of sVOEs/year Interval -13.0 to -0.5

SECONDARY outcome

Timeframe: From 6 months to 24 months post lovo-cel infusion

VOE-CR24, defined as complete resolution of VOE between 6 months and 24 months post lovo-cel infusion. All reported VOEs were also adjudicated by an independent Event Adjudication Committee for purposes of outcome analysis. VOEs were determined by adjudication committee after referring to protocol definition of VOE. The committee was responsible for VOE assessment and determining whether an event met criteria for a VOE for all reported events.

Outcome measures

Outcome measures
Measure	Group C n=32 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
Percentage of Group C Participants With Complete Resolution of VOE Between 6 and 24 Months Post Lovo-cel Infusion (VOE-CR24)	84.4 percentage of participants Interval 67.2 to 94.7

SECONDARY outcome

Timeframe: From 6 months to 24 months post lovo-cel infusion

sVOE-CR24, defined as complete resolution of sVOEs in 6 to 24 months post lovo-cel infusion compared to the 24 months prior to Informed Consent. All reported VOEs (including sVOEs) were adjudicated by an independent Event Adjudication Committee for purposes of outcome analysis. sVOE were determined by adjudication committee after referring to protocol definition of sVOE. The committee was responsible for VOE assessment and determining whether an event met criteria for an sVOE for all reported events.

Outcome measures

Outcome measures
Measure	Group C n=32 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
Percentage of Group C Participants With Complete Resolution of sVOEs Between 6 and 24 Months Post Lovo-cel Infusion (sVOE-CR24)	90.6 percentage of participants Interval 75.0 to 98.0

SECONDARY outcome

Timeframe: Up to 24 months post lovo-cel infusion

sVOE-75, defined as at least a 75% reduction in annualized sVOEs in the 24 months post lovo-cel infusion compared to the 24 months prior to Informed Consent. All reported VOEs (including sVOEs) were adjudicated by an independent Event Adjudication Committee for purposes of outcome analysis. sVOE were determined by adjudication committee after referring to protocol definition of sVOE. The committee was responsible for VOE assessment and determining whether an event met criteria for an sVOE for all reported events.

Outcome measures

Outcome measures
Measure	Group C n=32 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
Percentage of Group C Participants With At Least 75% Reduction in Annualized sVOEs (sVOE-75)	93.8 percentage of participants Interval 79.2 to 99.2

SECONDARY outcome

Timeframe: From post hospital discharge to Month 24

Change from baseline was calculated as annualized number of VOE-related hospital admissions during post-drug product infusion discharge through the last study visit minus annualized number of VOE related hospital admissions at baseline. Baseline was annualized number of VOE-related hospital admissions in 24 months prior to the Informed Consent.

Outcome measures

Outcome measures
Measure	Group C n=32 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
Change From Baseline in Annualized VOE-related Hospital Admissions in Group C Participants	-3.00 hospital admissions per year Interval -13.5 to -0.5

SECONDARY outcome

Timeframe: From post hospital discharge to Month 24

Change from baseline was calculated as annualized number of VOE-related hospital days during post-drug product infusion discharge through the last study visit minus annualized number of VOE related hospital days at baseline. Baseline was annualized number of VOE-related hospital days in 24 months prior to the Informed Consent.

Outcome measures

Outcome measures
Measure	Group C n=32 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
Change From Baseline in Annualized VOE-related Total Days Hospitalized in Group C Participants	-16.75 hospitalized days per year Interval -136.0 to -1.5

SECONDARY outcome

Timeframe: At Month 6, 12, 18, and 24 post lovo-cel infusion

Population: TP included participants who received lovo-cel. As per planned analysis data was analyzed and reported for TP Group C participants. Here, "number analyzed" refer to the participants who were evaluable at specified time points. Evaluable participants are defined as participants who have weighted average of non-transfused total Hb at Month 6, 12, 18 and 24.

Non-transfused total Hb was the total g/dL of HbS + HbF + HbA2 + HbAT87Q for participants without beta + allele or HbS + HbF + HbA2 + HbAT87Q + HbA for participants with beta + allele.

Outcome measures

Outcome measures
Measure	Group C n=36 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
Weighted Average of Non-transfused Total Hb in Group C Participants At Month 6	10.73 gram per deciliter (g/dL) Interval 5.1 to 13.1
Weighted Average of Non-transfused Total Hb in Group C Participants At Month 12	11.53 gram per deciliter (g/dL) Interval 5.1 to 14.4
Weighted Average of Non-transfused Total Hb in Group C Participants At Month 18	11.70 gram per deciliter (g/dL) Interval 9.6 to 15.1
Weighted Average of Non-transfused Total Hb in Group C Participants At Month 24	11.53 gram per deciliter (g/dL) Interval 9.2 to 15.4

SECONDARY outcome

Timeframe: At Month 6, 12, 18, and 24 post lovo-cel infusion

HbS % in non-transfused total Hb = (HbS/ non-transfused total Hb)\*100.

Outcome measures

Outcome measures
Measure	Group C n=36 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
Weighted Average of HbS Percentage (%) in Non-transfused Total Hb in Group C Participants At Month 6	50.17 percentage of non-transfused total HbS Interval 31.4 to 66.2
Weighted Average of HbS Percentage (%) in Non-transfused Total Hb in Group C Participants At Month 12	50.77 percentage of non-transfused total HbS Interval 31.4 to 68.1
Weighted Average of HbS Percentage (%) in Non-transfused Total Hb in Group C Participants At Month 18	50.51 percentage of non-transfused total HbS Interval 39.2 to 68.1
Weighted Average of HbS Percentage (%) in Non-transfused Total Hb in Group C Participants At Month 24	51.16 percentage of non-transfused total HbS Interval 37.8 to 61.7

SECONDARY outcome

Timeframe: At Month 6, 12, 18, and 24 post lovo-cel infusion

Population: TP included participants who received lovo-cel. As per planned analysis data was analyzed and reported for TP Group C participants. Here, "number analyzed" refer to the participants who were evaluable at specified time points. Evaluable participants are defined as participants who achieved \<= 70%, \<= 60%, and \<= 50% HbS at Month 6, 12, 18 and 24.

HbS % in non-transfused total Hb = (HbS/ non-transfused total Hb)\*100. The denominator of the percentage is based on the total number of participants who have non-missing value at the Visit.

Outcome measures

Outcome measures
Measure	Group C n=36 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
Percentage of Group C Participants Who Achieved <= 70%, <= 60%, and <= 50% Weighted Average of HbS % in Non-transfused Total Hb At Month 6:<=70% Weighted Average HbS	100.0 Percentage of participants
Percentage of Group C Participants Who Achieved <= 70%, <= 60%, and <= 50% Weighted Average of HbS % in Non-transfused Total Hb At Month 6:<=60% Weighted Average HbS	94.4 Percentage of participants
Percentage of Group C Participants Who Achieved <= 70%, <= 60%, and <= 50% Weighted Average of HbS % in Non-transfused Total Hb At Month 6:<=50% Weighted Average HbS	47.2 Percentage of participants
Percentage of Group C Participants Who Achieved <= 70%, <= 60%, and <= 50% Weighted Average of HbS % in Non-transfused Total Hb At Month 12:<=70% Weighted Average HbS	100 Percentage of participants
Percentage of Group C Participants Who Achieved <= 70%, <= 60%, and <= 50% Weighted Average of HbS % in Non-transfused Total Hb At Month 12:<=60% Weighted Average HbS	94.4 Percentage of participants
Percentage of Group C Participants Who Achieved <= 70%, <= 60%, and <= 50% Weighted Average of HbS % in Non-transfused Total Hb At Month 12:<=50% Weighted Average HbS	41.7 Percentage of participants
Percentage of Group C Participants Who Achieved <= 70%, <= 60%, and <= 50% Weighted Average of HbS % in Non-transfused Total Hb At Month 18:<=70% Weighted Average HbS	100 Percentage of participants
Percentage of Group C Participants Who Achieved <= 70%, <= 60%, and <= 50% Weighted Average of HbS % in Non-transfused Total Hb At Month 18:<=60% Weighted Average HbS	94.3 Percentage of participants
Percentage of Group C Participants Who Achieved <= 70%, <= 60%, and <= 50% Weighted Average of HbS % in Non-transfused Total Hb At Month 18:<=50% Weighted Average HbS	45.7 Percentage of participants
Percentage of Group C Participants Who Achieved <= 70%, <= 60%, and <= 50% Weighted Average of HbS % in Non-transfused Total Hb At Month 24:<=70% Weighted Average HbS	100 Percentage of participants
Percentage of Group C Participants Who Achieved <= 70%, <= 60%, and <= 50% Weighted Average of HbS % in Non-transfused Total Hb At Month 24:<=60% Weighted Average HbS	94.1 Percentage of participants
Percentage of Group C Participants Who Achieved <= 70%, <= 60%, and <= 50% Weighted Average of HbS % in Non-transfused Total Hb At Month 24:<=50% Weighted Average HbS	44.1 Percentage of participants

SECONDARY outcome

Timeframe: At Month 6, 12, 18, and 24 post lovo-cel infusion

HbAT87Q % in non-transfused total Hb was calculated as: HbAT87Q / non-transfused total Hb \*100.

Outcome measures

Outcome measures
Measure	Group C n=36 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
Weighted Average of HbAT87Q % in Non-transfused Total Hb in Group C Participants At Month 6	46.33 percentage of non-transfused total Hb Interval 25.9 to 63.0
Weighted Average of HbAT87Q % in Non-transfused Total Hb in Group C Participants At Month 12	46.25 percentage of non-transfused total Hb Interval 24.5 to 63.0
Weighted Average of HbAT87Q % in Non-transfused Total Hb in Group C Participants At Month 18	45.99 percentage of non-transfused total Hb Interval 24.5 to 59.0
Weighted Average of HbAT87Q % in Non-transfused Total Hb in Group C Participants At Month 24	45.05 percentage of non-transfused total Hb Interval 26.9 to 58.9

SECONDARY outcome

Timeframe: At Month 6, 12, 18, and 24 post lovo-cel infusion

Non-HbS percentage in non-transfused total Hb = \[(HbF + HbA2 + HbAT87Q)/ non-transfused total Hb\] \*100. For participants with beta + allele, HbA was also included in the calculated for "non-HbS" for samples taken \>= 60 days after last pRBC transfusion.

Outcome measures

Outcome measures
Measure	Group C n=36 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
Weighted Average of Non-HbS % in Non-transfused Total Hb in Group C Participants Month 6	49.83 percentage of non-HbS in total Hb Interval 33.8 to 68.6
Weighted Average of Non-HbS % in Non-transfused Total Hb in Group C Participants Month 12	49.23 percentage of non-HbS in total Hb Interval 31.9 to 68.6
Weighted Average of Non-HbS % in Non-transfused Total Hb in Group C Participants Month 18	49.49 percentage of non-HbS in total Hb Interval 31.9 to 60.8
Weighted Average of Non-HbS % in Non-transfused Total Hb in Group C Participants Month 24	48.84 percentage of non-HbS in total Hb Interval 38.3 to 62.2

SECONDARY outcome

Timeframe: From infusion up to Month 24

Population: TP included participants who received lovo-cel. As per planned analysis data was analyzed and reported for TP Group C participants.

Non-transfused total Hb was the total g/dL of HbS + HbF + HbA2 + HbAT87Q for participants without beta + allele or HbS + HbF + HbA2 + HbAT87Q + HbA for participants with beta + allele.

Outcome measures

Outcome measures
Measure	Group C n=36 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
Non-transfused Total Hb (g/dL) Over Time	11.80 g/dL Interval 6.6 to 16.2

SECONDARY outcome

Timeframe: From infusion up to Month 24

Population: TP included participants who received lovo-cel. As per planned analysis data was analyzed and reported for TP Group C participants.

HbS (%) in non-transfused total Hb = (HbS / non-transfused total Hb)\*100.

Outcome measures

Outcome measures
Measure	Group C n=36 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
HbS % in Non-transfused Total Hb Over Time	51.47 Percent Interval 29.1 to 62.0

SECONDARY outcome

Timeframe: From infusion up to Month 24

Population: TP included participants who received lovo-cel. As per planned analysis data was analyzed and reported for TP Group C participants.

HbAT87Q (%) in Non-transfused total Hb = (HbAT87Q / non-transfused total Hb)\*100.

Outcome measures

Outcome measures
Measure	Group C n=36 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
HbAT87Q % in Non-transfused Total Hb Over Time	46.01 Percent Interval 26.9 to 63.2

SECONDARY outcome

Timeframe: From infusion up to Month 24

Population: TP included participants who received lovo-cel. As per planned analysis data was analyzed and reported for TP Group C participants.

Non-HbS % in non-transfused total Hb = \[(HbF + HbA2 + HbAT87Q)/ non-transfused total Hb\] \*100.

Outcome measures

Outcome measures
Measure	Group C n=36 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
Non-HbS % of Non-transfused Total Hb Over Time	48.53 Percent Interval 38.0 to 70.9

SECONDARY outcome

Timeframe: Baseline, Month 12 and Month 24

Population: TP included participants who received lovo-cel. As per planned analysis data was analyzed and reported for TP Group C participants. Here, "number analyzed" refers to the participants who have absolute reticulocyte count at Baseline and at Months 12 and 24.

Reticulocytes are immature RBCs that develop in the bone marrow and circulate in the bloodstream for about a day before developing into mature RBCs. Due to the loss of mature RBCs during hemolysis, there is usually a high demand to produce new RBCs in subjects with SCD, resulting in higher than normal absolute reticulocyte counts. For this outcome Baseline is the first assessment on or after Informed Consent but before initiation of stem cell collection.

Outcome measures

Outcome measures
Measure	Group C n=36 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
Change From Baseline in Absolute Reticulocyte Count in Group C Participants Change at Month 12	-86.52 cells10^9 per liter (cells10^9/L) Interval -425.7 to 154.0
Change From Baseline in Absolute Reticulocyte Count in Group C Participants Change at Month 24	-77.95 cells10^9 per liter (cells10^9/L) Interval -344.8 to 91.0

SECONDARY outcome

Timeframe: Baseline, Month 12 and Month 24

Population: TP included participants who received lovo-cel. As per planned analysis data was analyzed and reported for TP Group C participants. Here, "number analyzed" refers to the participants who achieved % Reticulocyte/Erythrocytes at Baseline and at Months 12 and 24.

Reticulocytes are immature RBCs that develop in the bone marrow and circulate in the bloodstream for about a day before developing into mature RBCs. The fraction of reticulocytes/erythrocytes in the blood is normally 0.5% to 2.5%, and is increased when there is peripheral hemolytic anemia. Due to the loss of mature RBCs during hemolysis, there is usually a high demand to produce new RBCs in subjects with SCD, resulting in higher than normal reticulocyte counts. For this outcome, Baseline is the first assessment on or after Informed Consent but before initiation of stem cell collection.

Outcome measures

Outcome measures
Measure	Group C n=36 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
Change From Baseline in Percent (%) Reticulocyte/Erythrocytes in Group C Participants Change at Month 12	-4.595 Percent Interval -20.9 to 4.905
Change From Baseline in Percent (%) Reticulocyte/Erythrocytes in Group C Participants Change at Month 24	-4.847 Percent Interval -18.151 to 3.077

SECONDARY outcome

Timeframe: Baseline, Month 12 and Month 24

Population: TP included participants who received lovo-cel. As per planned analysis data was analyzed and reported for TP Group C participants. Here, "number analyzed" refers to the participants who achieved total bilirubin count at Baseline and at Months 12 and 24.

Reduction of red blood cell sickling with lovo-cel has the potential to reduce or eliminate downstream complications, including hemolysis. Total Bilirubin is a marker of RBC hemolysis and so increases in Total Bilirubin levels suggests increased hemolysis. For this outcome, Baseline is the first assessment on or after Informed Consent but before initiation of stem cell collection.

Outcome measures

Outcome measures
Measure	Group C n=36 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
Change From Baseline in Total Bilirubin in Group C Participants Change at Month 12	-1.850 milligram per deciliter (mg/dL) Interval -6.6 to 1.1
Change From Baseline in Total Bilirubin in Group C Participants Change at Month 24	-1.800 milligram per deciliter (mg/dL) Interval -5.8 to 0.7

SECONDARY outcome

Timeframe: Baseline, Month 12 and Month 24

Population: TP included participants who received lovo-cel. As per planned analysis data was analyzed and reported for TP Group C participants. Here, "number analyzed" refers to the participants who achieved haptoglobin count at Baseline and at Months 12 and 24.

Reduction of red blood cell sickling with lovo-cel has the potential to reduce or eliminate downstream complications, including hemolysis. Haptoglobin is a marker of RBC hemolysis and so increases in Haptoglobin levels suggests increased hemolysis. For this outcome, Baseline is the first assessment on or after Informed Consent but before initiation of stem cell collection. It should be noted that Baseline haptoglobin levels may be impacted by a range of factors that result in variability, including (but not limited to) other therapies that a participant receives (such as blood transfusions or hydroxyurea), which limit interpretability of these data.

Outcome measures

Outcome measures
Measure	Group C n=36 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
Change From Baseline in Haptoglobin in Group C Participants Change at Month 12	0.0 mg/dL Interval -26.0 to 110.0
Change From Baseline in Haptoglobin in Group C Participants Change at Month 24	0.0 mg/dL Interval -69.0 to 174.0

SECONDARY outcome

Timeframe: Baseline, Month 12 and Month 24

Population: TP included participants who received lovo-cel. As per planned analysis data was analyzed and reported for TP Group C participants. Here, "number analyzed" refers to the participants who achieved lactate dehydrogenase count at Baseline and at Months 12 and 24.

Reduction of red blood cell sickling with lovo-cel has the potential to reduce or eliminate downstream complications, including hemolysis. Lactate Dehydrogenase is a marker of RBC hemolysis and so increases in LDH levels suggests increased hemolysis, For this outcome, Baseline is the first assessment on or after Informed Consent but before initiation of stem cell collection.

Outcome measures

Outcome measures
Measure	Group C n=36 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
Change From Baseline in Lactate Dehydrogenase (LDH) in Group C Participants Change at Month 12	-147.0 units per liter (U/L) Interval -873.0 to 102.0
Change From Baseline in Lactate Dehydrogenase (LDH) in Group C Participants Change at Month 24	-145.0 units per liter (U/L) Interval -846.0 to 218.0

SECONDARY outcome

Timeframe: Baseline, Month 24

Particulate intracellular iron causes shortening of the magnetic resonance relaxation parameter T2 due to microscopic magnetic field inhomogeneity. A myocardial T2 value of 40 msec, which equates to 0.50 mg/g of dry weight iron has widely been used as the normal mean. Myocardial T2. Values below 20 msec are considered abnormal, and values below 10 msec indicate high risk of cardiac morbidity and mortality. For this outcome, Baseline was defined as the first assessment on or after Informed Consent but before initiation of stem cell collection. If no records at screening, the last assessment prior to Informed Consent was used. Note: while data are provided for this outcome measure, the results for this outcome are not anticipated to be fully mature until extended participant long-term follow-up in Study LTF-307 has been achieved. The results presented below should be interpreted in that context.

Outcome measures

Outcome measures
Measure	Group C n=18 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
Change From Baseline in Cardiac T2* on MRI in Group C Participants	0.00 milliseconds (msec) Interval -18.0 to 13.0

SECONDARY outcome

Timeframe: Baseline, Month 12 and Month 24

Population: TP included participants who received lovo-cel. As per planned analysis data was analyzed and reported for TP Group C participants. Here, "number analyzed" refers to the participants who achieved serum ferritin count at Baseline and at Months 12 and 24.

Serum ferritin is commonly used for an indirect estimation of body iron stores. Although sensitive, it is not specific for iron overload as it can be elevated in a variety of infectious and inflammatory states, and in the presence of cytolysis. For this outcome, Baseline was the first assessment on or after Informed Consent but before initiation of stem cell collection. Note: while data are provided for this outcome measure, the results for this outcome are not anticipated to be fully mature until extended participant long-term follow-up in Study LTF-307 has been achieved. The results presented below should be interpreted in that context.

Outcome measures

Outcome measures
Measure	Group C n=36 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
Change From Baseline in Serum Ferritin in Group C Participants Change at Month 12	1133.9 nanogram per milliliter (ng/mL) Interval -927.0 to 9596.0
Change From Baseline in Serum Ferritin in Group C Participants Change at Month 24	604.6 nanogram per milliliter (ng/mL) Interval -1328.0 to 7498.0

SECONDARY outcome

Timeframe: Baseline, Month 24

Population: TP included participants who received lovo-cel. As per planned analysis data was analyzed and reported for TP Group C participants. Here, "Overall number of participants analyzed" signifies participants who achieved liver iron concentration at Month 24.

Liver Iron Concentration of greater than 15 mg per gram dry weight (mg/g) is associated with an increased risk of hepatic disease and cardiac toxicity, whereas levels between 7 to 15 mg/g enhance the risk of hepatic fibrosis and endocrine complications. Liver Iron Concentration of greater than 1.8 mg/g dry weight is considered abnormal; however, organ damage generally does not occur with levels less than 7 mg/g. For this outcome, Baseline was defined as the first assessment on or after Informed Consent but before initiation of stem cell collection. If no records at screening, the last assessment prior to Informed Consent was used. Note: while data are provided for this outcome measure, the results for this outcome are not anticipated to be fully mature until extended participant long-term follow-up in Study LTF-307 has been achieved. The results presented below should be interpreted in that context.

Outcome measures

Outcome measures
Measure	Group C n=21 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
Change From Baseline in Liver Iron Concentration (LIC) by Magnetic Resonance Imaging (MRI) in Group C Participants	1.100 milligram per gram (mg/g) Interval -10.2 to 9.93

SECONDARY outcome

Timeframe: From 6 months through 24 months post lovo-cel infusion

Change from baseline was calculated as annualized volume of pRBC transfusions in 6 to 24 months post lovo-cel infusion - annualized volume of pRBC transfusions at baseline. Baseline was the annualized volume of pRBC transfusion in the 24 months prior to the Informed Consent.

Outcome measures

Outcome measures
Measure	Group C n=34 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
Change From Baseline in Annualized Volume of pRBC Transfusions in Group C Participants	-23.60 mL/kg/year Interval -522.1 to 43.3

SECONDARY outcome

Timeframe: From 6 months through 24 months post lovo-cel infusion

Change from baseline was calculated as annualized number of pRBC transfusions in 6 to 24 months post lovo-cel infusion - annualized number of pRBC transfusions at baseline. Baseline was the annualized number of pRBC transfusion in the 24 months prior to the Informed Consent.

Outcome measures

Outcome measures
Measure	Group C n=34 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
Change From Baseline in Annualized Number of Packed Red Blood Cell (pRBC) Transfusions in Group C Participants	-3.25 number of pRBC transfusions/year Interval -17.0 to 7.1

SECONDARY outcome

Timeframe: Baseline, Month 12 and Month 24

Erythropoietin is a hormone produced mainly by the kidneys in response to hypoxia, which can be caused by anemia. Patients with SCD typically produce higher than normal levels of serum erythropoietin. Baseline is the first assessment on or after Informed Consent but before initiation of stem cell collection.

Outcome measures

Outcome measures
Measure	Group C n=12 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
Change From Baseline in Erythropoietin Levels in Group C Participants Change at Month 12	-26.20 units per liter (U/L) Interval -286.0 to 3.0
Change From Baseline in Erythropoietin Levels in Group C Participants Change at Month 24	-16.55 units per liter (U/L) Interval -276.4 to 42.0

SECONDARY outcome

Timeframe: Baseline, Month 24

LVEF is the central measure of left ventricular systolic function. LVEF is the fraction of chamber volume ejected in systole (stroke volume) in relation to the volume of the blood in the ventricle at the end of diastole (end-diastolic volume). This was measured by ECHO. Baseline was the first assessment on or after Informed Consent but before initiation of stem cell collection. If no records at screening, the last assessment prior to Informed Consent was used. Note: while data are provided for this outcome measure, the results for this outcome are not anticipated to be fully mature until extended participant long-term follow-up in Study LTF-307 has been achieved. The results presented below should be interpreted in that context.

Outcome measures

Outcome measures
Measure	Group C n=35 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
Change From Baseline in Cardiac-pulmonary Function Via Left Ventricular Ejection Fraction (LVEF) in Group C Participants	-0.50 percent Interval -25.9 to 11.0

SECONDARY outcome

Timeframe: Baseline, Month 12 and Month 24

Population: TP included participants who received lovo-cel. As per planned analysis data was analyzed and reported for TP Group C participants. Here, "number analyzed" refers to the participants who had serum transferrin receptor count at Baseline and at Months 12 and 24.

Transferrin is a circulating iron carrier protein, delivering iron to cells via the transferrin receptor, and levels of serum transferrin receptor have been used as an indicator of excess iron in the body. Additionally, the transferrin receptor is highly expressed in erythroblasts, and increased levels of the soluble form (serum transferrin receptor) have been shown to be associated with increased levels of erythropoiesis. Baseline is the first assessment on or after Informed Consent but before initiation of stem cell collection.

Outcome measures

Outcome measures
Measure	Group C n=36 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
Change From Baseline in Serum Transferrin Receptor in Group C Participants Change at Month 12	-0.409 milligrams per deciliter (mg/dL) Interval -3.35 to 0.09
Change From Baseline in Serum Transferrin Receptor in Group C Participants Change at Month 24	-0.422 milligrams per deciliter (mg/dL) Interval -1.64 to 0.13

SECONDARY outcome

Timeframe: Baseline, Month 12 and Month 24

Population: TP included participants who received lovo-cel. As per planned analysis data was analyzed and reported for TP Group C participants. Here, "number analyzed" refers to the participants who had renal function at Baseline and at Months 12 and 24.

eGFR was calculated by chronic kidney disease epidemiology collaboration (CKD-EPI) formula for participants \>=18 years of age and Schwartz formula was used for participants \<18 years of age. Baseline is the first assessment on or after Informed Consent but before initiation of stem cell collection. If no records at screening, the last assessment prior to Informed Consent was used. Note: while data are provided for this outcome measure, the results for this outcome are not anticipated to be fully mature until extended participant long-term follow-up in Study LTF-307 has been achieved. The results presented below should be interpreted in that context.

Outcome measures

Outcome measures
Measure	Group C n=36 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
Change From Baseline in Renal Function as Measured by Estimated Glomerular Filtration Rate (eGFR) in Group C Participants Change at Month 24	-7.71 milliliter/minute/1.73 square meter Interval -58.7 to 43.8
Change From Baseline in Renal Function as Measured by Estimated Glomerular Filtration Rate (eGFR) in Group C Participants Change at Month 12	-2.20 milliliter/minute/1.73 square meter Interval -34.8 to 55.7

SECONDARY outcome

Timeframe: Baseline, Month 24

Population: TP included participants who received lovo-cel. As per planned analysis data was analyzed and reported for TP Group C participants. Here, "Overall number of participants analyzed" refers to the participants who had shift at baseline for TRJV at Month 24

TRJV over time for each participant was classified into 2 categories: \<2.5 m/sec versus \>=2.5 m/sec. Higher value of TRJV indicates worse result. A TRJV value of \>2.5 m/s was associated with a higher risk of complications, especially in participants with Sickle Cell Disease due to hemolysis and pulmonary hypertension. Baseline was the first assessment on or after Informed Consent but before initiation of stem cell collection. If no records at screening, the last assessment prior to Informed Consent was used. Note: while data are provided for this outcome measure, the results for this outcome are not anticipated to be fully mature until extended participant long-term follow-up in Study LTF-307 has been achieved. The results presented below should be interpreted in that context.

Outcome measures

Outcome measures
Measure	Group C n=13 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
Number of Participants With Shift From Baseline in Cardiac-pulmonary Function Via Echocardiogram (Tricuspid Regurgitant Jet Velocity [TRJV]) in Group C Participants TRJV at Baseline (<2.5 m/sec) to TRJV at Month 24 (<2.5 m/sec)	5 Participants
Number of Participants With Shift From Baseline in Cardiac-pulmonary Function Via Echocardiogram (Tricuspid Regurgitant Jet Velocity [TRJV]) in Group C Participants TRJV at Baseline (>=2.5 m/sec) to TRJV at Month 24 (<2.5 m/sec)	4 Participants
Number of Participants With Shift From Baseline in Cardiac-pulmonary Function Via Echocardiogram (Tricuspid Regurgitant Jet Velocity [TRJV]) in Group C Participants TRJV at Baseline (<2.5 m/sec) to TRJV at Month 24 (>=2.5 m/sec)	0 Participants
Number of Participants With Shift From Baseline in Cardiac-pulmonary Function Via Echocardiogram (Tricuspid Regurgitant Jet Velocity [TRJV]) in Group C Participants TRJV at Baseline (>=2.5 m/sec) to TRJV at Month 24 (>=2.5 m/sec)	4 Participants

SECONDARY outcome

Timeframe: Baseline, Month 24

Population: TP included participants who received lovo-cel. As per planned analysis data was analyzed and reported for TP Group C participants. Here, "Overall number of participants analyzed" refers to the participants who had shift from baseline in PFTs at Month 24

PFTs over time of each participant were classified into one of the five categories: normal, obstructive, restrictive, mixed obstructive and restrictive and isolated low DLco (carbon monoxide diffusing capacity). Only non-zero values are reported here. Baseline was the first assessment on or after Informed Consent but before initiation of stem cell collection. If no records at screening, the last assessment prior to Informed Consent was used. Note: while data are provided for this outcome measure, the results for this outcome are not anticipated to be fully mature until extended participant long-term follow-up in Study LTF-307 has been achieved. The results presented below should be interpreted in that context.

Outcome measures

Outcome measures
Measure	Group C n=32 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
Number of Participant With Shift From Baseline in Cardiac-pulmonary Function Via Pulmonary Function Tests (PFTs) in Group C Participants Restrictive at Baseline to Normal at Month 24	2 Participants
Number of Participant With Shift From Baseline in Cardiac-pulmonary Function Via Pulmonary Function Tests (PFTs) in Group C Participants Restrictive at Baseline to Restrictive at Month 24	12 Participants
Number of Participant With Shift From Baseline in Cardiac-pulmonary Function Via Pulmonary Function Tests (PFTs) in Group C Participants Restrictive at Baseline to Isolated low DLco at Month 24	1 Participants
Number of Participant With Shift From Baseline in Cardiac-pulmonary Function Via Pulmonary Function Tests (PFTs) in Group C Participants Restrictive at Baseline to Not Specified at Month 24	3 Participants
Number of Participant With Shift From Baseline in Cardiac-pulmonary Function Via Pulmonary Function Tests (PFTs) in Group C Participants Isolated low DLco at Baseline to Restrictive at Month 24	1 Participants
Number of Participant With Shift From Baseline in Cardiac-pulmonary Function Via Pulmonary Function Tests (PFTs) in Group C Participants Isolated low DLco at Baseline to Isolated low DLco at Month 24	2 Participants
Number of Participant With Shift From Baseline in Cardiac-pulmonary Function Via Pulmonary Function Tests (PFTs) in Group C Participants Not Specified at Baseline to Normal at Month 24	2 Participants
Number of Participant With Shift From Baseline in Cardiac-pulmonary Function Via Pulmonary Function Tests (PFTs) in Group C Participants Not Specified at Baseline to Restrictive at Month 24	1 Participants
Number of Participant With Shift From Baseline in Cardiac-pulmonary Function Via Pulmonary Function Tests (PFTs) in Group C Participants Not Specified at Baseline to Isolated low DLco at Month 24	1 Participants
Number of Participant With Shift From Baseline in Cardiac-pulmonary Function Via Pulmonary Function Tests (PFTs) in Group C Participants Not Specified at Baseline to Not Specified at Month 24	7 Participants

SECONDARY outcome

Timeframe: Baseline, Month 12 and Month 24

The 6-minute walk test measures the distance in meters walked during 6 minutes and can be used to assess pulmonary function. Baseline was the first assessment on or after Informed Consent but before initiation of stem cell collection.

Outcome measures

Outcome measures
Measure	Group C n=25 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
Change From Baseline in Meters Walked During 6-minute Walk Test in Group C Participants Change at Month 12: Distance Walked in 6 Minutes	-7.13 meters Interval -62.6 to 44.4
Change From Baseline in Meters Walked During 6-minute Walk Test in Group C Participants Change at Month 24: Distance Walked in 6 Minutes	-0.65 meters Interval -46.9 to 91.0

SECONDARY outcome

Timeframe: Baseline, Month 24

The PROMIS-57 profile was a self-reported questionnaire assessing quality of life in various 7 domains (pain interference, physical function, sleep disturbance, Ability to participate in social roles and activities, anxiety, depression, and fatigue) in participants \>=18 years old.These 7 domains are scored on a 5-point Likert scale and converted into standardized T-scores with a mean of 50 and a standard deviation of 10 based on a US general population. The higher of the T-score: the better of physical function, satisfaction with participation in social roles, and ability of participate in social roles in activities; The higher of the T-score: the worse of anxiety, depression, fatigue, sleep disturbance, and pain interference. A negative value indicates improvement, and a positive value indicates no improvement in condition. Baseline was the first assessment on or after Informed Consent but before initiation of stem cell collection.

Outcome measures

Outcome measures
Measure	Group C n=28 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
Change From Baseline in Patient-reported Quality of Life as Measured by Patient Reported Outcomes Measurement Information System-57 (PROMIS-57): Domain (T- Score) in Group C Participants Change at Month 24 (T-score): Pain Interference	-7.40 T-score Interval -25.5 to 13.5
Change From Baseline in Patient-reported Quality of Life as Measured by Patient Reported Outcomes Measurement Information System-57 (PROMIS-57): Domain (T- Score) in Group C Participants Change at Month 24 (T-score): Physical Function	5.10 T-score Interval -6.5 to 17.7
Change From Baseline in Patient-reported Quality of Life as Measured by Patient Reported Outcomes Measurement Information System-57 (PROMIS-57): Domain (T- Score) in Group C Participants Change at Month 24 (T-score): Sleep Disturbance	-4.15 T-score Interval -18.8 to 16.2
Change From Baseline in Patient-reported Quality of Life as Measured by Patient Reported Outcomes Measurement Information System-57 (PROMIS-57): Domain (T- Score) in Group C Participants Change at Month 24 (T-score): Ability to participate in social roles and activities	10.60 T-score Interval 7.8 to 20.9
Change From Baseline in Patient-reported Quality of Life as Measured by Patient Reported Outcomes Measurement Information System-57 (PROMIS-57): Domain (T- Score) in Group C Participants Change at Month 24 (T-score): Anxiety	0.00 T-score Interval -24.3 to 20.4
Change From Baseline in Patient-reported Quality of Life as Measured by Patient Reported Outcomes Measurement Information System-57 (PROMIS-57): Domain (T- Score) in Group C Participants Change at Month 24 (T-score): Depression	0.00 T-score Interval -20.3 to 17.4
Change From Baseline in Patient-reported Quality of Life as Measured by Patient Reported Outcomes Measurement Information System-57 (PROMIS-57): Domain (T- Score) in Group C Participants Change at Month 24 (T-score): Fatigue	-7.70 T-score Interval -30.2 to 8.5

SECONDARY outcome

Timeframe: Baseline, Month 24

The PROMIS-57 profile was a self-reported questionnaire assessing quality of life in various domains in participants \>=18 years old. Pain intensity was scored from 0 to 10, with higher scores indicating greater pain intensity. A negative value indicates improvement in pain intensity and a positive value indicates no improvement or worsening in pain intensity. Baseline was the first assessment on or after Informed Consent but before initiation of stem cell collection.

Outcome measures

Outcome measures
Measure	Group C n=26 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
Change From Baseline in Patient-reported Quality of Life as Measured by PROMIS-57: Pain Intensity Score in Group C Participants	-2.0 Score on a scale Interval -6.0 to 4.0

SECONDARY outcome

Timeframe: Baseline, Month 24

The PROMIS-49 profile was a self-reported questionnaire assessing quality of life in various 6 domains (physical function mobility, peer relationships, pain interference, anxiety, depression, and fatigue) in participants \<=18 years old. These 6 domains are scored on a 5-point Likert scale and converted into standardized T-scores with a mean of 50 and a standard deviation of 10 based on a US general population. The higher of the T-score, the better of physical function mobility, and peer relationships; The higher of the T-score, the worse of anxiety, depression symptoms, fatigue, and pain interference. A negative value indicates improvement, and a positive value indicates no improvement in condition. Baseline was the first assessment on or after Informed Consent but before initiation of stem cell collection.

Outcome measures

Outcome measures
Measure	Group C n=4 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
Change From Baseline in Patient-reported Quality of Life as Measured by Patient Reported Outcomes Measurement Information System- 49 (PROMIS-49)): Domain (T- Score) in Group C Participants Change at Month 24 (T-score): Physical Function Mobility	7.15 T-score Interval -10.1 to 13.0
Change From Baseline in Patient-reported Quality of Life as Measured by Patient Reported Outcomes Measurement Information System- 49 (PROMIS-49)): Domain (T- Score) in Group C Participants Change at Month 24 (T-score): Anxiety	-0.40 T-score Interval -9.1 to 9.4
Change From Baseline in Patient-reported Quality of Life as Measured by Patient Reported Outcomes Measurement Information System- 49 (PROMIS-49)): Domain (T- Score) in Group C Participants Change at Month 24 (T-score): Depressive Symptoms	0.95 T-score Interval -5.1 to 8.5
Change From Baseline in Patient-reported Quality of Life as Measured by Patient Reported Outcomes Measurement Information System- 49 (PROMIS-49)): Domain (T- Score) in Group C Participants Change at Month 24 (T-score): Fatigue	-5.70 T-score Interval -24.5 to 0.0
Change From Baseline in Patient-reported Quality of Life as Measured by Patient Reported Outcomes Measurement Information System- 49 (PROMIS-49)): Domain (T- Score) in Group C Participants Change at Month 24 (T-score): Peer Relationships	2.45 T-score Interval -2.2 to 10.6
Change From Baseline in Patient-reported Quality of Life as Measured by Patient Reported Outcomes Measurement Information System- 49 (PROMIS-49)): Domain (T- Score) in Group C Participants Change at Month 24 (T-score): Pain Interference	-2.95 T-score Interval -13.6 to 2.9

SECONDARY outcome

Timeframe: Baseline, Month 24

The PROMIS-49 profile was a self-reported questionnaire assessing quality of life in various domains in participants \<=18 years old. Pain intensity was scored from 0 to 10, with higher scores indicating greater pain intensity. A negative value indicates improvement in pain intensity and a positive value indicates no improvement or worsening in pain intensity. Baseline was the first assessment on or after Informed Consent but before initiation of stem cell collection.

Outcome measures

Outcome measures
Measure	Group C n=4 Participants Plerixafor mobilization and apheresis were used for collection of rescue cells, and drug product. Participants received treatment of lovo-cel manufactured with autologous CD34+ HSPCs collected by plerixafor mobilization and apheresis transduced with BB305 lentiviral vector encoding the human beta-A-T87Q globin gene using a further refined manufacturing process similar to commercial manufacturing.
Change From Baseline in Patient-reported Quality of Life as Measured by PROMIS-49: Pain Intensity Score in Group C Participants	-4.0 Score on a Scale Interval -7.0 to 0.0

Adverse Events

Group A

Serious events: 9 serious events

Other events: 9 other events

Deaths: 0 deaths

Group B

Serious events: 2 serious events

Other events: 2 other events

Deaths: 0 deaths

Group C

Serious events: 33 serious events

Other events: 43 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Study Medical Director

bluebird bio, Inc

Phone: 339-499-9300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place