Bluebird Bio has announced that it is just one step away from its first ever approval for its first ever product, Zynteglo, a gene therapy treatment for beta thalassemia.
The groundbreaking one-time treatment promises to permanently free beta thalassemia patients from the frequent blood transfusions currently necessary, and works by restoring working copies of the β-globin gene into a patient’s own haematopoietic (blood) stem cells (HSCs).
The European Medicines Agency’s CHMP committee has recommended conditional marketing authorisation for Zynteglo (autologous CD34+ cells encoding β A-T87Q-globin gene), setting it up for full European Commission approval within the next few months.
Today’s confirmation comes a few days after two European charities prematurely announced the news.
The recommendation is a huge milestone for the Cambridge, Mass-based biotech, and confirms its place among the vanguard of new gene therapy companies.
The treatment is recommended for patients 12 years and older with transfusion-dependent β-thalassemia (TDT) who do not have a β0/β0 genotype, for whom haematopoietic stem cell (HSC) transplantation is appropriate but a human leukocyte antigen (HLA)-matched related HSC donor is not available. If approved, Zynteglo, formerly referred to as LentiGlobin for TDT, will be the first gene therapy to treat TDT.
David Davidson
“The goal of treatment with Zynteglo is to enable patients with transfusion-dependent β-thalassemia to produce haemoglobin at sufficient levels to allow lifelong independence from blood transfusions,” said David Davidson, chief medical officer, Bluebird Bio.
“The positive CHMP opinion for Zynteglo is a crucial step toward providing what would be the first one-time gene therapy for people living with TDT. We share this achievement with the TDT community, patients and clinical investigators whose dedication made it possible. We look forward to the upcoming decision from the European Commission.”
“For many of my patients, living with TDT means a lifetime of chronic blood transfusions, iron chelation therapy and supportive treatments to manage anaemia and other serious complications of this disease,” said Professor Franco Locatelli, Professor of Paediatrics, Sapienza University of Rome, Italy and Director, Department of Paediatric Haematology/Oncology and Cell and Gene Therapy, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.
“The burden placed on these patients and their families is significant. It extends beyond immediate health implications to their daily lives, which are affected by the symptoms, hospitalisations and necessary chronic care required for TDT.”
The company is already in an advanced state of preparation for launching the gene therapy in Europe. This includes the first specialist therapy sites set up to perform the collection and removal of the patient’s own haematopoietic (blood) stem cells (HSCs), called apheresis.
The next stage is called transduction, and involves these HSCs being taken to a lab where a lentiviral vector is used to insert the β A-T87Q-globin gene into the patient’s HSCs. The patient then receives chemotherapy to prepare their bone marrow for the modified HSCs, which are re-administered through an infusion.
Bluebird has been unusual in deciding to file in Europe ahead of the US – partly because of the higher incidence of beta-thalassemia in the region, but also because of the EMA’s openness to working with biotech firms on novel therapies.
“The EMA’s collaborative approach and innovative programmes have been instrumental in improving timely access of new medicines to patients with significant unmet needs, like those who are living with TDT,” said Anne-Virginie Eggimann, senior vice president of regulatory science at bluebird bio.
Bluebird is also well advanced in talks with Europe’s healthcare payers about a novel arrangement for paying for the therapy.
The company’s chief executive Nick Leschly laid out the company’s plans earlier this year, suggesting the therapy’s cost would have a maximum ‘ceiling value’ of $2.1m, and could be paid for in five instalments.
Unlike some other disease areas, the company is confident that healthcare systems will be willing to pay this price, as it should work out as cheaper than paying for lifelong blood transfusions.
Analysts William Blair estimated last year that Zynteglo’s revenues could exceed $800m in worldwide revenue in TDT, but this will depend on whether forthcoming data shows it can provide curative treatment in the harder-to-treat sub-groups, known as ß0/ß0 patients.
The company’s trials all look promising, but have only studied the therapies affects in a small number of patients, over a relatively short period of time.
The positive CHMP opinion is supported by 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 an ongoing phase 3 Northstar-2 (HGB-207) and Northstar-3 (HGB-212) studies, and the long-term follow-up study LTF-303.
The approval will also increase speculation about a possible M&A move for the company from a major biopharma company. Fellow US gene therapy company Spark was recently acquired by Roche for $4.3bn, part of a wave of deals in recent months, which have confirmed gene therapy’s future.