bluebird bio Announces a European Conditional Approval of Its Gene Therapy ZYNTEGLO™ for Transfusion-Dependent β-Thalassemia  

Zynteglo™ from bluebird bio Gets European Conditional Approval

  • European marketing authorization for Zynteglo follows the fastest assessment of an advanced therapy medicinal product (ATMP) as part of the European Medicines Agency’s Priority Medicines (PRIME) program.
  • Zynteglo is bluebird bio’s first gene therapy to gain regulatory approval.

Gene therapy is, indeed, moving towards the clinic to provide cures; to save people from an early death from life-threatening diseases that declared victories over all the available treatments. Today we witness the announcement from bluebird bio (BLUE) that the European Commission (EC) has granted conditional marketing authorization for Zynteglo™–  a gene therapy for patients 12 years and older with transfusion-dependent β-thalassemia who do not have a β00 genotype, for whom hematopoietic stem cell (HSC) transplantation is appropriate but a human leukocyte antigen (HLA)-matched related HSC donor is not available.

bluebird bio will continue the country-by-country reimbursement process to help ensure access to Zynteglo for appropriate patients.

About Transfusion-dependent β-thalassemia (TDT) 

TDT is a severe genetic disease caused by mutations in the β-globin gene that result in reduced or absent hemoglobin.

People with TDT maintain hemoglobin levels through lifelong chronic blood transfusions in order to survive. However, these transfusions carry the risk of progressive multi-organ damage due to unavoidable iron overload.

About Zynteglo™

Zynteglo is a one-time gene therapy that addresses the underlying genetic cause of TDT and offers patients 12 years and older who do not have a β00 genotype the potential to become transfusion independent, once achieved are expected to be life-long.

bluebird bio’s gene therapy product Zynteglo was reviewed as part of the European Medicines Agency’s (EMA) programs that support therapies expected to offer a major advantage over existing treatments, or to benefit patients who remain without treatment options to save their lives. The PRIME and Adaptive Pathway programs allowed for early and enhanced dialogue and accelerated assessment of Zynteglo, which was completed on the shortest timetable for an ATMP by the EMA to date.

An Expert Comment

It was interesting and enlightening to read the comment from Professor Franco Locatelli, M.D., Ph.D., Professor of Pediatrics, Sapienza University of Rome, Italy, and Director, Department of Pediatric Hematology/Oncology and Cell and Gene Therapy, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy. He said, “As one of the investigators in the clinical studies of Zynteglo, I have witnessed firsthand the hope this gene therapy can provide to patients and their families who have often been managing this disease and transfusions for years, often for decades,” said. “This approval by the European Commission means we now have a gene therapy for certain patients with TDT that has the potential to transform lives by offering the possibility of a transfusion-free future.”

Zynteglo adds functional copies of a modified form of the β-globin gene (βA-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 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 βA-T87Q-globin gene into the patient’s HSCs. This step is called transduction. Before their modified HSCs are returned through infusion, a patient receives chemotherapy to prepare their bone marrow for the modified HSCs that now carry the βA-T87Q-globin gene. Once they have the βA-T87Q-globin gene they gain the potential to produce HbAT87Q, which is gene therapy-derived-hemoglobin, at levels that eliminate or significantly reduce the need for transfusions.  

Due to the highly technical and specialized nature of administering gene therapy in rare diseases, bluebird bio is working with select qualified treatment centers that have expertise in stem cell transplant and treating patients with TDT to provide Zynteglo.

The conditional marketing authorization is valid in all 28 member states of the EU as well as Iceland, Liechtenstein and Norway.

Data, Safety and Efficacy of Zynteglo™

Zynteglo’s safety, efficacy, durability and the conditional marketing authorization are all well supported by data from the Phase 1/2 HGB-205 study and the completed Phase 1/2 Northstar (HGB-204) study. There is also 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, as of the data cut off of December 13, 2018.

Data from Phase 1/2 HGB-205study demonstrated that 75% of patients who used Zynteglo, who do not have a β0genotype, achieved transfusion independence. This means they had not received a transfusion for at least 12 months or more and maintained weighted hemoglobin ≥9 g/dL. In Phase 1/2 Northstar study 80% of patients who do not have a β0genotype achieved transfusion independence.

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 the gene therapy product.

Additional AEs observed in clinical studies were consistent with the known side effects of HSC collection and bone marrow ablation with busulfan, including SAEs of venous-occlusive disease.

For details please see the Summary of Product Characteristics (SmPC).

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.

In addition to PRIME designation, Zynteglo received Orphan Medicinal Product designation from the EC for β-thalassemia intermedia and major, which includes TDT. On the other hand, the U.S. Food and Drug Administration granted Zynteglo Orphan Drug status and Breakthrough Therapy designation for the treatment of TDT.

Prohost Observations 

It is refreshing to have another gene therapy in the clinic from bluebird bio, for Transfusion-Dependent β-Thalassemia; after the approval of Spark Therapeutics’ (ONCE) gene therapy product Luxturna for an inherited retinal disease; as well as the approval  of Novartis’ (NVS) gene therapy Zolgensma®for pediatric patients less than 2 years of age with spinal muscular atrophy (SMA) with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene.  

The three firms are Prohost picks. Spark was acquired by Roche for which they paid a high premium to get. Both bluebird bio and Novartis remain part of our Prohost Portfolio.

We congratulate our subscribers who followed our decision to add Novartis and bluebird bio to our portfolio on time before their gene therapies were granted approvals. 

BLUE is UP $7.09 at the time we posted this news. 

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