First gene therapy recommended for approval in the EU for TDT
Treatment with ZYNTEGLO has been shown to help eliminate the need for chronic blood transfusions in patients with TDT
ZYNTEGLO is bluebird bio’s first gene therapy submitted for regulatory approval
The CHMP’s positive opinion will now be reviewed by the
TDT is a severe genetic disease caused by mutations in the β-globin gene that result in reduced or absent hemoglobin. In order to survive, people with TDT maintain hemoglobin levels through lifelong chronic blood transfusions. These transfusions carry the risk of progressive multi-organ damage due to unavoidable iron overload.
“The goal of treatment with ZYNTEGLO is to enable patients with
transfusion-dependent β-thalassemia to produce hemoglobin at sufficient
levels to allow lifelong independence from blood transfusions,” said
“For many of my patients, living with TDT means a lifetime of chronic
blood transfusions, iron chelation therapy and supportive treatments to
manage anemia and other serious complications of this disease,” said
“The present management of TDT, including regular blood transfusions
every two to four weeks and daily iron chelation therapy has many
psychological and social consequences, including marginalization and
isolation. And in many patients TDT-related morbidities can lead to a
shortened life span. Therefore, it is with great anticipation and
eagerness that the international patient community has closely followed
the dynamic rejuvenation of scientific interest and research of gene
therapy in TDT over the last few years,” said Dr.
ZYNTEGLO adds functional copies of a modified form of the β-globin gene (β A-T87Q-globin gene) into a patient’s own hematopoietic (blood) stem cells (HSCs). This means there is no need for donor HSCs from another person as is required for allogeneic HSC transplantation (allo-HSCT). A patient’s HSCs are collected and removed from the body through a process called apheresis. These HSCs are taken to a lab where a lentiviral vector is used to insert the β A-T87Q-globin gene into the patient’s HSCs. This step is called transduction. Before their modified HSCs are returned, the patient receives chemotherapy to prepare their bone marrow for the modified HSCs, which are returned through an infusion. Once a patient has the β A-T87Q-globin gene they have the potential to produce HbAT87Q, which is gene therapy- derived-hemoglobin, at levels that significantly reduce or eliminate the need for transfusions.
“The EMA’s collaborative approach and innovative programs have been
instrumental in improving timely access of new medicines to patients
with significant unmet needs, like those who are living with TDT,” said
ZYNTEGLO was reviewed under an accelerated assessment timeline as part of the EMA’s Priority Medicines (PRIME) and Adaptive Pathways programs, which support medicines that may offer a major therapeutic advantage over existing treatments, or benefit patients without treatment options.
Data Supporting Clinical Profile of ZYNTEGLO
The positive CHMP opinion is supported by efficacy, safety and durability data from the Phase 1/2 HGB-205 study and the completed Phase 1/2 Northstar (HGB-204) study as well as available data from the ongoing Phase 3 Northstar-2 (HGB-207) and Northstar-3 (HGB-212) studies, and the long-term follow-up study LTF-303.
In the Phase 3 Northstar-2 and Northstar-3 studies, a refined
manufacturing process was used to produce ZYNTEGLO and was intended to
further improve the clinical results observed in the Northstar study. As
Non-serious adverse events (AEs) observed during clinical trials that were attributed to ZYNTEGLO were hot flush, dyspnoea, abdominal pain, pain in extremities and non-cardiac chest pain. One serious adverse event (SAE) of thrombocytopenia was considered possibly related to ZYNTEGLO.
Additional AEs observed in clinical studies were consistent with the known side effects of HSC and bone marrow ablation with busulfan including SAEs of veno-occlusive disease.
ZYNTEGLO continues to be evaluated in the ongoing Phase 3 Northstar-2 and Northstar-3 studies and the long-term follow-up study LTF-303.
About bluebird bio, Inc.
bluebird bio is pioneering gene therapy with purpose. From our Cambridge, Mass., headquarters, we’re developing gene therapies for severe genetic diseases and cancer, with the goal that people facing potentially fatal conditions with limited treatment options can live their lives fully. Beyond our labs, we’re working to positively disrupt the healthcare system to create access, transparency and education so that gene therapy can become available to all those who can benefit.
bluebird bio is a human company powered by human stories. We’re putting our care and expertise to work across a spectrum of disorders by researching cerebral adrenoleukodystrophy, sickle cell disease, transfusion-dependent β-thalassemia and multiple myeloma using three gene therapy technologies: gene addition, cell therapy and (megaTAL-enabled) gene editing.
bluebird bio has additional nests in Seattle, Wash.; Durham, N.C.; and Zug, Switzerland. For more information, visit bluebirdbio.com.
ZYNTEGLO and LentiGlobin are trademarks of bluebird bio.
The full common name for ZYNTEGLO: A genetically modified autologous CD34+ cell enriched population that contains hematopoietic stem cells transduced with lentiviral vector encoding the β A-T87Q-globin gene.
This release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding the Company’s plans and expectations for the regulatory approval, and commercialization for ZYNTEGLO™ (autologous CD34+ cells encoding β A-T87Q-globin gene, formerly LentiGlobin™ in TDT) to treat TDT, and the potential implications of clinical data for patients. Any forward-looking statements are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: the risk that our MAA submitted for ZYNTEGLO may not be approved by the
Source: bluebird bio, Inc.