Betibeglogene autotemcel


Betibeglogene autotemcel, sold under the brand name Zynteglo, is a medication for the treatment for beta thalassemia, a rare and potentially debilitating blood disorder. It was developed by Bluebird Bio and was given breakthrough therapy designation by the U.S. Food and Drug Administration in February 2015. It was approved for medical use in the European Union in May 2019.
The most serious side effect observed is thrombocytopenia.

Medical uses

Betibeglogene autotemcel is indicated for the treatment of adults and adolescents 12 years and older with transfusion-dependent β thalassaemia who do not have a β0/β0 genotype, for whom haematopoietic stem cell transplantation is appropriate but a human leukocyte antigen -matched related HSC donor is not available.
Betibeglogene autotemcel is made individually for each person out of stem cells collected from their blood, and must only be given to the person for whom it is made. It is given as an infusion into a vein and the dose depends on the bodyweight of the recipient.
Before betibeglogene autotemcel is given, the recipient will receive conditioning chemotherapy treatment to clear their bone marrow of cells.
To make betibeglogene autotemcel, the stem cells taken from the recipient's blood are modified by a virus that carries working copies of the beta-globin gene into the cells. When these modified cells are given back to the recipient, they are transported in the bloodstream to the bone marrow where they start to make healthy red blood cells that produce beta-globin. The effects of betibeglogene autotemcel are expected to last for the patient's lifetime.

Mechanism of action

Beta thalassemia is caused by mutations to or deletions of the HBB gene leading to reduced or absent synthesis of the beta chains of hemoglobin that result in variable outcomes ranging from severe anemia to clinically asymptomatic individuals. LentiGlobin BB305 is a lentiviral vector which inserts a functioning version of the HBB gene into a patient's blood-producing hematopoietic stem cells ex vivo. The resulting engineered HSC cells are then reintroduced to the patient.

Development history

In early clinical trials several patients with beta thalassemia, who usually require frequent blood transfusions to treat their disease, were able to forgo blood transfusions for extended periods of time. In 2018, results from phase 1-2 trials suggested that of 22 patients receiving Lentiglobin gene therapy, 15 were able to stop or reduce regular blood transfusions.

History

It was designated an orphan drug by the European Medicines Agency and by the U.S. Food and Drug Administration in 2013.
It was approved for medical use in the European Union in May 2019.

Name

The international nonproprietary name is betibeglogene autotemcel.