Gene Therapy for Life-limiting Blood Disorder Becomes Commercially Available
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bluebird bio Inc. have announced that their gene therapy for the blood disorder transfusion-dependent β-thalassemia (TDT), ZYNTEGLOTM, is commercially available for the first time.
ZYNTEGLOTM, or autologous CD34+ cells encoding βA-T87Q-globin gene, is the first and only one-time gene therapy for patients >12 years of age with TDT and is now available in Germany.
What is TDT?
TDT is an inherited genetic disorder that is typically diagnosed within the first two years of life. It is characterized by impaired production of the beta chains of hemoglobin and underproduction of hemoglobin. Patients are subsequently oxygen deficient and suffer from chronic anemia in addition to other associated health conditions that can adversely affect quality of life. The current treatment approach for TDT is regular blood transfusion, sometimes in frequencies of two to four times per week. Blood transfusions carry their own risks, in that they can lead to progressive multi-organ damage due to iron overload, musculoskeletal diseases, respiratory diseases and metabolic disorders.
ZYNTEGLOTM's journey
ZYNTEGLOTM is a one-time gene therapy that is custom created for each individual patient. The therapy involves removal of the patient's own stem cells from their blood. The cells are then modified in laboratory and transduced with a lentiviral vector that carries functional copies of the βA-T87Q-globin gene. The cells are intravenously returned to the patient and are carried to the bone marrow where they engraft and subsequently produce red blood cells with functional beta-globin. This process addresses the underlying cause of the genetic disorder, and, being a one-time therapy, the effects of ZYNTEGLOTM are anticipated to last for the patient's lifetime.
The efficacy of ZYNTEGLOTM has been assessed in four clinical trials and subjects continue to be monitored in a long-term study follow-up up of fifteen years. The studies demonstrated that after a one-time treatment with ZYNTEGLOTM, most patients became transfusion-independent, meaning they no longer rely on blood transfusions to increase their working red blood cell count. Based on these data, ZYNTEGLOTM received "conditional authorization" by the European Medicines Agency (EMA) in May 2019, as it was decided that the benefits of the gene therapy outweigh the associated risks of use.
Nonetheless, conditional authorization denotes that there is further data to come regarding the gene therapy. bluebird bio Inc. must provide this data to the EMA who will continue to assess the therapy's market status.
As ZYNTEGLOTM is a gene therapy produced using a virus, there is a potential risk of cancer resulting from unanticipated changes to the genetic material of the subject. No such cases have been reported to date, however longitudinal assessment is likely to reveal the true magnitude of such risk.
ZYNTEGLOTM delivery
Gene therapies are extremely technical in terms of administration and patient monitoring. Thus, bluebird bio Inc. is collaborating with an array of institutions that possess expertise in stem cell transplants to ensure the therapy can be made available to patients. It is a collaboration with the University Hospital of Heidelberg that has enabled the therapy to become commercially available in Germany. The conditional marketing authorization for ZYNTEGLOTM granted by the EMA is valid in the 28 member states of the EU, in addition to Iceland, Liechtenstein and Norway.
“For patients with TDT, lifelong chronic blood transfusions are required in order to survive. We are thrilled to announce that ZYNTEGLOTM will now be available for patients in the EU living with this severe disease,” says Alison Finger, chief commercial officer, bluebird bio Inc. “In addition to confirming manufacturing readiness of our partner, apceth Biopharma GmbH, bluebird has also submitted a dossier to the Joint Federal Committee (G-BA) in Germany for drug benefit assessment."
A transfusion-independent life – but at what cost?
It's well-acknowledged that even chemically synthesized small molecule drugs can cost millions of pounds to manufacture and bring to market. So, what's the price tag on a one-time gene therapy?
€1.575 million (or $1.77 million).
According to the press release, bluebird has entered into a value-based payment agreement with several statutory health insurers in Germany to create payment plans for patients, ensuring that TDT suffers and their healthcare providers have access to the gene therapy. The proposed payment model consists of five payments made in equal instalments, with the first payment required at the time of infusion. The remaining four annual payments are only to be made if the patient does in fact become transfusion independent as a result of the therapy.
Finger says “In addition to confirming manufacturing readiness of our partner, apceth Biopharma GmbH, bluebird has also submitted a dossier to the Joint Federal Committee (G-BA) in Germany for drug benefit assessment. We would like to thank our collaborators for their commitment in helping us transform the healthcare system by accepting innovative payment models, and we look forward to treating our first commercial patient soon.”
U.S. next?
Currently the gene therapy is unavailable in the U.S. for TDT, however the company is in the process of biologics license application submission that is anticipated to complete in the first half of this year.
