Bluebird Bio announced late last week that the European Medicines Agency has accepted its gene therapy LentiGlobin for accelerated review.
The filing is particularly significant because Bluebird has chosen to submit its product in Europe first, and if approved, would be the first of the company’s groundbreaking gene therapies to reach the market.
The accelerated review status means the EMA could reach a decision in as little as five months for the one-time therapy, which could soon treat adolescents and adults with transfusion-dependentβ-thalassemia (TDT) with a non-β0/β0 genotype, an inherited rare blood disorder.
Caused by a mutation in the β-globin gene, patients with TDT struggle to produce red blood cells, which leads to severe anaemia.
The routine care available for these patients consists of a lifelong regimen of chronic blood transfusions, typically administered every 2-5 weeks, which help suppress symptoms of the disease.
However these transfusions come with unavoidable iron overload that can result in damage to vital organs, so patients with TDT require a further treatment regimen called iron chelation therapy.
Another option for TDT patients is bone marrow transplant (allogeneic haematopoietic stem cell transplant or allo-HSCT), which has the potential to correct the genetic deficiency.
While potentially curative, allo-HSCT is associated with a risk of transplant-related mortality and graft failure, leading to immunological complications. Many patients with TDT are not considered optimal candidates for allo-HSCT due to lack of donor match, disease complications and/or age.
LentiGlobin has, however, been shown to reduce or even eliminate entirely the need for blood transfusions, freeing patients from the disease.
“People living with transfusion-dependent β-thalassemia require frequent blood transfusions that are life-saving but may lead to complications, including organ failure due to iron overload,” said David Davidson, chief medical officer, Bluebird Bio.
“The acceptance of our marketing authorisation application for LentiGlobin is a milestone that advances us toward our goal of providing to patients the first one-time gene therapy that addresses the underlying genetic cause of TDT.”
The therapy itself works by inserting a functional human beta-globin gene into a patient’s own haematopoietic stem cells ex vivo, and then transplanting those modified cells into the patient’s blood stream through infusion.
It has shown promise for TDT patients, with data revealing seven out of eight patients involved in the phase 1/2 study (Northstar) are transfusion-free and producing normal levels of haemoglobin.
The biotech is also conducting a long-term safety and efficacy follow-up study (LTF-303) for those who have participated in the clinical trials for both TDT and sickle cell disease, the latter being another therapy area that Bluebird is looking to treat with its gene therapy.
LentiGlobin is already part of the EMA’s Adaptive Pathways pilot programme, which aims to improve timely access for patients to new medicines.
Meanwhile, the FDA has granted an orphan drug status and a breakthrough therapy designation for LentiGlobin for the treatment of TDT.
Celgene and biotech company Acceleron also have a contender heading to market – their luspatercept is a first-in-class erythoid maturation agent that can regulate late-stage red blood cell development, although this won’t produce the potentially curative results seen with Bluebird’s gene therapy.