PARAMETER

DATA

Manufacturer

Bluebird bio (Netherlands) B.V.

Transgene

βA-T87Q-globin gene

Indication

Zynteglo is indicated for the treatment of patients 12 years and older with transfusion-dependent β-thalassaemia (TDT) who do not have a β0/β0 genotype, for whom haematopoietic stem cell (HSC) transplantation is appropriate but a human leukocyte antigen (HLA)-matched related HSC donor is not available.

Virus and Serotype

 Lentiviral vector (LVV)

Cell Substrate

Hematopoietic stem cells (HSCs)

Manufacturing platform

Lentiviral vector: BB305 LVV is produced by transient transfection. BB305 LVV buds from the production cells, is harvested, purified via chromatography, and formulated prior to frozen storage. The LVV manufacturing process begins with thawing HEK293T cells from the working cell bank (WCB). These cells are transfected with plasmid BB305 and packaging plasmids and incubated at a specified temperature and duration. Subsequently, the supernatants containing the LVV are collected. This crude harvest is clarified by filtration, purified by chromatography, concentrated and formulated. The sterile filtered BB305 LVV is filled in vials.

Transduced autologous cells: The manufacturing process starts from the starting material, the hematopoietic progenitor cells obtained by apheresis (HPC-A) and follows a continuous process up to formulation and filling of the FP. HPC-A is subject to a platelet wash and CD34+ cell enrichment. The purpose of the CD34+ cell enrichment step is to separate CD34+ cells from other cells. After enrichment, a pre-transduction stimulation is performed. The purpose of the Pre-Transduction Stimulation Culture process step is to make cells receptive to transduction. The cells are then transduced with BB305 LVV. Cells are then washed and re-suspended. These washed cells constitute the active substance. The process is continuous until formulation of the FP.

Dose in vial/final container

1.2-20 × 10⁶ cells/mL dispersion for infusion

Dose/patient

Dose: {N.N} × 10⁶ CD34+ cells/kg

The minimum recommended dose of Zynteglo is 5.0 × 10⁶ CD34+ cells/kg. In clinical studies doses up to 20 × 10⁶ CD34+ cells/kg have been administered.

NCT

TRIAL PHASE

SUBJECTS ENROLLED

STUDY TITLE

COUNTRIES

NCT02151526

1, 2

7

A study evaluating the safety and efficacy of lentiglobin BB305 drug product in β-Thalassemia major (also referred to as Transfusion-dependent β-Thalassemia [TDT]) and Sickle Cell Disease         

France

NCT01745120

1, 2

19

A study evaluating the safety and efficacy of the LentiGlobin BB305 drug product in β-Thalassemia major participants     

United States, Australia, Thailand

NCT02906202

3

23

A study evaluating the efficacy and safety of the LentiGlobin® BB305 drug product in subjects with transfusion-dependent β-Thalassemia, who do not have a β0/β0 genotype          

United States, France, Germany, Italy, Thailand, United Kingdom

NCT03207009

3

18

A study evaluating the efficacy and safety of the LentiGlobin® BB305 drug product in subjects with transfusion-dependent β-thalassemia

United States, France, Germany,  Greece, Italy, United Kingdom

NCT02633943

-

94

Long-term follow-up of subjects with hemoglobinopathies treated with ex vivo gene therapy     

United States, Australia, France, Thailand, Italy, Germany, United Kingdom