Rare Daily Staff

The European Commission granted conditional approval for Bluebird Bio’s Zynteglo, a one-time gene therapy for certain patients 12 years and older with transfusion-dependent beta-thalassemia, a condition that results in reduced or absent hemoglobin essential for the transport of oxygen within the body.

The conditional marketing authorization is valid in all 28 member states of the European Union as well as Iceland, Liechtenstein, and Norway. The treatment is authorized for transfusion-dependent thalassemia (TDT) patients who do not have a beta 0/beta 0 genotype, for whom hematopoietic stem cell transplantation is appropriate but a matched related donor is not available.

“EC approval of Zynteglo is a milestone,” said Nick Leschly, chief bluebird. “Our first product approval is a humbling moment for all of us at Bluebird.” The company said it will continue the country-by-country reimbursement process to help ensure access to Zynteglo for appropriate patients.

TDT is a severe genetic disease caused by mutations in the beta-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 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 beta 0/beta 0 genotype the potential to become transfusion independent, which once achieved is expected to be lifelong.

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

“We welcome European Commission authorization for the first gene therapy for TDT,” said Androulla Eleftheriou, Thalassemia International Federation executive director. “This achievement means the TDT community now has another treatment option that may provide new hope for people living with TDT who have been managing their disease through chronic transfusions.”

Zynteglo was reviewed as part of the European Medicines Agency’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 PRIME and Adaptive Pathway programs allowed for early and enhanced dialogue and accelerated assessment of Zynteglo, which was completed on the shortest timetable to date for an advanced therapy medicinal product.

The conditional marketing authorization 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 the data cut off of December 13, 2018.

Data from phase 1/2 HGB-205 showed that 75 percent of patients who do not have a beta 0/beta 0 genotype achieved transfusion independence, meaning they had not received a transfusion for at least 12 months or more and maintained weighted hemoglobin ≥9 g/dL. In the phase 1/2 Northstar study, 80 percent of patients who do not have a beta 0/ beta 0 genotype achieved transfusion independence.

These 11 patients (three from HGB-205 and eight from Northstar) continued to maintain transfusion independence, which at the time of data cut off was for a duration of 21 to 56 months. Five patients in Northstar-2 were evaluable for transfusion independence. Of these five, 80 percent achieved transfusion independence.

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 adverse events observed in clinical studies were consistent with the known side effects of HSC collection and bone marrow ablation with busulfan, including serious adverse events 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.

Zynteglo received an Orphan Medicinal Product designation from the EC for the treatment of beta-thalassemia intermedia and major, which includes TDT. The U.S. Food and Drug Administration granted ZYNTEGLO Orphan Drug status and Breakthrough Therapy designation for the treatment of TDT.

Photo: Nick Leschly, CEO of Bluebird Bio

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