2 April 2019 - - The Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion recommending conditional marketing authorisation for Zynteglo (autologous CD34+ cells encoding β A-T87Q-globin gene), a gene therapy for patients 12 years and older with transfusion-dependent β-thalassemia who do not have a β0/β0 genotype, for whom hematopoietic stem cell transplantation is appropriate but a human leukocyte antigen -matched related HSC donor is not available, US-based bluebird bio, Inc. (NASDAQ: BLUE) said.

If approved, Zynteglo, formerly referred to as LentiGlobin for TDT, will be the first gene therapy to treat TDT.

The CHMP's positive opinion will now be reviewed by the European Commission, which has the authority to grant marketing authorization for Zynteglo in the European Union.

A CHMP positive opinion is one of the final steps before the EC decides on whether to authorize a new medicine. A final decision by the EC for Zynteglo is anticipated in 2Q19.

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.

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.

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.

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.

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.

As of September 14, 2018, data from Phase 1/2 Northstar showed that 80 % (n=8/10) of patients who do not have a β0/β0 genotype achieved transfusion independence, meaning they had not received a transfusion for at least 12 months and maintained hemoglobin ≥9 g/dL.

These eight patients had maintained transfusion independence for a median duration of 38 months (21 44 months) at the time of data cut off.

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 of September 14, 2018, the median (min max) total hemoglobin for patients six months after Zynteglo infusion in the Northstar-2 study was 11.9 (8.4, 13.3) g/dL.

Non-serious adverse events 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 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.

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 in 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.