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.[1][2] It was approved for medical use in the European Union in May 2019.[3]

Betibeglogene autotemcel
Clinical data
Trade namesZynteglo
Other namesLentiGlobin BB305, autologous CD34+ cells encoding βA-T87Q-globin gene
License data
Routes of
administration		Infusion
ATC code
  • none
Legal status
Legal status
  • In general: ℞ (Prescription only)
Identifiers
UNII

The most serious side effect observed is thrombocytopenia (low blood levels of platelets).[3]

Medical uses

Betibeglogene autotemcel is indicated for the treatment of adults and adolescents 12 years and older with transfusion-dependent β thalassaemia (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.[3]

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.[3] It is given as an infusion (drip) into a vein and the dose depends on the bodyweight of the recipient.[3]

Before betibeglogene autotemcel is given, the recipient will receive conditioning chemotherapy treatment to clear their bone marrow of cells.[3]

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.[3] 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.[3] The effects of betibeglogene autotemcel are expected to last for the patient's lifetime.[3]

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.[4] LentiGlobin BB305 is a lentiviral vector which inserts a functioning version of the HBB gene into a patient's blood-producing hematopoietic stem cells (HSC) ex vivo. The resulting engineered HSC cells are then reintroduced to the patient.[5][6]

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.[7][8][9] 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.[10][11]

History

It was designated an orphan drug by the European Medicines Agency (EMA) and by the U.S. Food and Drug Administration (FDA) in 2013.[3][12]

It was approved for medical use in the European Union in May 2019.[3]

Name

The international nonproprietary name (INN) is betibeglogene autotemcel.[13]

See also

References
  1. "Ten things you might have missed Monday from the world of business". The Boston Globe. 3 February 2015. Retrieved 13 February 2015.
  2. "Lentiviral vectors". Monday, 8 July 2019
  3. "Zynteglo EPAR". European Medicines Agency (EMA). 25 March 2019. Retrieved 16 August 2019. This article incorporates text from this source, which is in the public domain.
  4. Cao, Antonio; Galanello, Renzo (21 January 2010). "Beta-thalassemia". Genetics in Medicine. 12 (2): 61–76. doi:10.1097/GIM.0b013e3181cd68ed. PMID 20098328.
  5. Negre O, et al. (2015). "Preclinical evaluation of efficacy and safety of an improved lentiviral vector for the treatment of β-thalassemia and sickle cell disease" (PDF). Current Gene Therapy. 15 (1): 64–81. doi:10.2174/1566523214666141127095336. PMC 4440358. PMID 25429463.
  6. Thompson A, et al. (2014). "Initial Results from the Northstar Study (HGB-204): A Phase 1/2 Study of Gene Therapy for β-Thalassemia Major Via Transplantation of Autologous Hematopoietic Stem Cells Transduced Ex Vivo with a Lentiviral βΑ-T87Q -Globin Vector (LentiGlobin BB305 Drug Product)". Blood. 124 (21): 549. doi:10.1182/blood.V124.21.549.549.
  7. Cavazzana-Calvo M, Payen E, Negre O, et al. (2010). "Transfusion independence and HMGA2 activation after gene therapy of human β-thalassaemia". Nature. 467 (7313): 318–22. doi:10.1038/nature09328. PMC 3355472. PMID 20844535.
  8. Winslow, Ron (8 December 2015). "New Gene Therapy Shows Promise for Lethal Blood Disease". The Wall Street Journal. Retrieved 13 February 2015.
  9. (8 December 2014) bluebird bio Announces Data Demonstrating First Four Patients with β-Thalassemia Major Treated with LentiGlobin are Transfusion-Free Yahoo News, Retrieved 17 May 2015
  10. Thompson, Alexis (19 April 2018). "Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia". New England Journal of Medicine. 378 (16): 1479–1493. doi:10.1056/NEJMoa1705342. PMID 29669226.
  11. Stein, Rob (18 April 2018). "Gene Therapy For Inherited Blood Disorder Reduced Transfusions". NPR. Retrieved 4 March 2019.
  12. "Autologous CD34+ hematopoietic stem cells transduced with LentiGlobin BB305 lentiviral vector encoding the human BA-T87Q-globin gene Orphan Drug Designations and Approvals". U.S. Food and Drug Administration (FDA). 18 March 2013. Retrieved 8 June 2020.
  13. World Health Organization (2020). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 83". WHO Drug Information. 34 (1): 34.
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