Each person inherits features in the form of genes, which are made up of a molecule called DNA. Genetic diseases involve problems with the functioning genes. Our gene therapy technology intends to make up for genetic defects by creating a functioning copy of the genes that express functional proteins and correct or address the underlying cause of the disease. We believe gene therapy has the potential to provide transformative, disease-modifying effects – potentially with life-long clinical benefits, based on a single administration.
leading the revolution –
how our gene therapy works
Our gene therapy process works by genetically modifying a patient’s own cells by adding a functional copy of the gene of interest. We have extensive expertise in viral vector design and manufacturing and transduction, which we have developed into a potent gene therapy platform with potentially broad applications in a wide variety of indications with significant medical needs.
Adrenoleukodystrophy (ALD) is a rare X-linked metabolic disorder caused by mutations in the ABCD1 gene which result in a deficiency in adrenoleukodystrophy protein (ALDP) and subsequent accumulation of very long chain fatty acids (VLCFA). VLCFA accumulation occurs in plasma and all tissue types but primarily affects the adrenal cortex and white matter of the brain and spinal cord, leading to a range of clinical outcomes. The most severe form of ALD, the inflammatory cerebral phenotype known as cerebral ALD (CALD), involves a progressive destruction of myelin, the protective sheath of the nerve cells in the brain that are responsible for thinking and muscle control. Symptoms of CALD usually occur in early childhood and progress rapidly if untreated, leading to severe loss of neurological function and eventual death in most patients.
bluebird bio is developing the investigational gene therapy Lenti-D drug product for the treatment of CALD. The Phase 2/3 Starbeam Clinical Study (ALD-102) is assessing the efficacy and safety of Lenti-D in boys up to 17 years of age with CALD. The study involves transplantation with a patient’s own stem cells, which are modified to contain a functioning copy of the ABCD1 gene. This gene addition should result in the production of functional ALDP, a protein critical for the breakdown of VLCFAs. Buildup of VLCFAs in the central nervous system contributes to neurodegeneration in CALD.
The primary efficacy endpoint for the Starbeam Clinical Study (ALD-102) is the proportion of patients who are alive and have none of six major functional disabilities (MFDs) at 24 months post treatment. MFDs are the six most severe disabilities from the Neurologic Function Score (NFS) and are of particular clinical importance, because they severely compromise a patient’s ability to function independently. They are: loss of communication, cortical blindness, tube feeding, total incontinence, wheelchair dependence, and complete loss of voluntary movement.
We presented the first, interim data from 17 treated patients in the Starbeam study at the American Academy of Neurology (AAN) Annual Meeting 2016.
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encouraging clinical data support our gene therapy’s potential
Our LentiGlobin® BB305 product candidate aims to treat transfusion-dependent β-thalassemia (also known as β-thalassemia major) and severe sickle cell disease (SCD). LentiGlobin works by inserting a functional human beta-globin gene into a patient’s own hematopoietic stem cells outside the body (ex vivo) and then transplanting those modified cells into the patient’s blood stream through infusion, also known as autologous stem cell transplantation.
A unique amino acid substitution in the beta-globin gene in LentiGlobin confers important anti-sickling properties to help potentially address the most severe forms of sickle cell disease. Promising results from a preclinical proof-of-concept study using gene therapy to treat sickle cell disease were published in Science.
We currently have three ongoing studies evaluating our LentiGlobin therapy for the treatment of transfusion-dependent β-thalassemia and severe SCD – the Northstar Study in transfusion-dependent β-thalassemia, the HGB-205 study in transfusion-dependent β-thalassemia or severe SCD and the HGB-206 study in severe SCD. As we continue to gather a growing body of data for LentiGlobin, we are learning and better understanding the potential clinical benefit our therapy can have on patients suffering from these diseases.
transfusion-dependent β-thalassemia (β-thalassemia major)
At the 57th American Society of Hematology (ASH) 2015 Annual Meeting, we presented data on 17 patients with transfusion-dependent β-thalassemia from the Northstar and HGB-205 studies. Findings include:
The data presented at the 2015 ASH Annual Meeting build on the data previously presented at the 20th Annual Congress of the European Hematology Association (EHA) and the 2014 American Society of Hematology Annual Meeting.
severe sickle cell disease
Also at the 2015 ASH Annual Meeting, we presented updated data on the first ever patient with severe SCD treated with gene therapy from our HGB-205 study and the first data on patients with severe SCD from our HGB-206 study.
The safety profile in the infused patients is consistent with autologous transplantation and no drug product-related grade >3 adverse events have been reported.
learn how gene therapy works to potentially treat β-thalassemialearn more about β-thalassemia learn more about Sickle cell disease