Beti-Cel Becomes the First Lentiviral Vector Gene Therapy in the U.S.

Hans-Peter Kiem, MD, PhD - August 17, 2022

The approval of beti-cel represents a huge step forward for beta thalassemia patients, giving them the option to pursue a one-and-done treatment approach.

Today the FDA approved betibeglogene autotemcel (beti-cel), a bespoke gene therapy to treat the underlying cause of beta thalassemia in adult and pediatric patients who require regular red blood cell transfusions. The approval makes beti-cel, marketed as Zynteglo, the first lentiviral vector gene therapy for patients with a severe genetic disease in the U.S. 

Beta thalassemia is an inherited blood disorder characterized by the deficiency of adult hemoglobin. Beti-cel, developed by bluebird bio, adds functional copies of a modified form of the β-globin gene (βA-T87Q-globin gene) into a patient’s own hematopoietic (blood) stem cells to correct that deficiency. Once the patient has the modified gene, their body has the potential to produce beti-cel-derived adult hemoglobin at levels that may eliminate or vastly reduce the need for regular blood transfusions. 

The approval of beti-cel represents a huge step forward for beta thalassemia patients, giving them the option to pursue a one-and-done treatment approach. Currently, patients require chronic transfusions that carry the risk of progressive multi-organ damage due to unavoidable iron overload; alternately, a small subset of patients with a matched sibling donor may currently pursue an allogenic hematopoietic stem cell transplant. 

Results from phase III studies showed that 89% of evaluable patients across ages and genotypes achieved transfusion independence (no longer needing red blood cell transfusions for at least 12 months while maintaining a weighted average Hb of at least 9 g/dL). bluebird bio is also conducting a long-term follow-up study to monitor safety and efficacy for people who have participated in bluebird bio-sponsored beti-cel clinical studies through 15 years post treatment. 

A second lentiviral vector gene therapy from bluebird bio, elivaldogene autotemcel (eli-cel) for cerebral adrenoleukodystrophy (CALD), has a Prescription Drug User Fee Act (PDUFA) date of Sept. 16. 

Dr. Kiem is president of ASGCT. He is also a professor of medicine and pathology and director of the stem cell and gene therapy program at the University of Washington, and the Stephanus Family Endowed Chair for Cell and Gene Therapy at the Fred Hutchinson Cancer Center.