bluebird bio’s gene therapy gains EU approvalPublished: June 6, 2019
The European Commission has granted conditional marketing authorization for bluebird bio’s gene therapy Zynteglo, for treating patients with transfusion-dependent beta-thalassemia. The conditional marketing authorization is valid in all 28 member states of the EU as well as Iceland, Liechtenstein and Norway.
Zynteglo, previously known as lentiglobin, is a cell-based gene therapy where autologous CD34+ cells from patients are transduced ex vivo with a lentiviral vector encoding βA-T87Q-globin gene. Following transplantation of these gene-corrected stem cells into patients, patients are monitored for the production of gene therapy-derived hemoglobin (Hb) which increases Hb levels.
Transfusion-dependent beta-thalassemia (TDT) is an inherited blood disorder caused by a mutation in the beta-globin chain resulting in ineffective red blood cell production. Anemia caused by TDT is corrected by blood transfusions, however, regular blood transfusions leads to iron overload.
bluebird’s one-time gene therapy provides hope for a category of TDT patients above 12 years; those who do not have a β0/β0 genotype for whom hematopoietic stem cell transplantation is appropriate but a human leukocyte antigen (HLA)-matched related HSC donor is not available.
Like Novartis, which gained FDA approval last month for Zolgensma, its spinal muscular atrophy gene therapy, bluebird bio has also proposed a pricing plan for spreading payments across five instalments over five years.
Although the company has not disclosed its price yet, analysts expect it to be between €450,000 and €1 million ($500,000 – $1.12m).
The regulatory approval was based on efficacy, safety and durability data from various clinical studies which are summarized below:
1) Completed Phase 1/2 HGB-205 study: Data showed that 75% (n=3/4) of patients who received the gene therapy did not have to receive a transfusion for at least 12 months or more post-transplant.
2) Completed Phase 1/2 Northstar (HGB-204): 80% (n=8/10) of patients achieved transfusion independence.
These 11 patients (three from HGB-205 and eight from HGB-204) continued to maintain transfusion independence, which at the time of data cut off was for a duration of 21–56 months.
3) Ongoing Phase 3 trials; Northstar-2 (HGB-207) and Northstar-3 (HGB-212): 80% (n=4/5) achieved transfusion independence.
4) Long-term follow-up study (LTF-303): Eligible patients from the above trials will be monitored long-term, for an additional 13 years. That is, 15 years post-transfusion. No investigative drug will be administered during this period.
Zynteglo-related non-serious adverse events reported were hot flush, breathing difficulty, abdominal pain, pain in extremities and non-cardiac chest pain. Thrombocytopenia was one serious adverse event reported which was related to Zynteglo. The company will continue evaluating the ongoing Phase 3 Northstar-2 and Northstar-3 studies and the long-term follow-up study LTF-303.
The European Medicines Agency (EMA) evaluated the data based on the Priority Medicines (PRIME) and Adaptive Pathways programs, which were introduced for therapies that may offer a major therapeutic advantage over existing treatments, or benefit patients without treatment options. These routes allowed for early and accelerated assessment of Zynteglo. It has thus become the first advanced therapy medicinal product to undergo the fastest assessment by the EMA to date.
Due to the highly technical and specialized nature of administering gene therapy in rare diseases, bluebird bio is also working with selected qualified treatment centers to administer Zynteglo. It will also continue the country-by-country reimbursement process to help ensure access the therapy to all eligible patients.
Nick Leschly, bluebird CEO commented: “EC approval of ZYNTEGLO is a milestone that represents the dedication and commitment of clinical investigators, healthcare providers, patients and their families, and our employees, all of whom have helped advance this treatment from concept to an approved therapy. Our first product approval is a humbling moment for all of us at bluebird, and we look forward to continuing our work with the TDT community and health systems to bring this important treatment to patients.”
Source: bluebird bio Announces EU Conditional Marketing Authorization for ZYNTEGLO™ (autologous CD34+ cells encoding βA-T87Q-globin gene) Gene Therapy for Patients 12 Years and Older with Transfusion-Dependent β-Thalassemia Who Do Not Have β0/β0 Genotype; Press Release