Recent Approvals, New Barriers

Betibeglogene autotemcel (beti-cel) is a 1-time gene therapy that adds functional copies of a modified form of the beta-globin gene into a patient’s own HSCs. The gene therapy medicinal product (GTMP) received conditional approval by the European Medicines Agency (EMA) in 2019 and approval by the US Food and Drug Administration (FDA) in 2022 for treatment of patients with beta-thalassemia who require regular red blood cell transfusions.2,3

Although these approvals represent an extraordinary achievement, recent developments in the field reveal how challenging it is to provide broad access to such treatments.

Continue Reading

Akin to other GTMPs, beti-cel was approved based on data from small registrational studies, with short follow-up and no comparison to standard of care, whether allo-HSCT or supportive care. As a result, post-authorization safety and efficacy studies are still needed to fully characterize safety and efficacy profiles, as exemplified by recent reports of adverse events.4,5 However, at the time of the review, the benefit to risk ratio of treatment with beti-cel remained favorable for patients with TDT.

Cost-Effectiveness Conundrum

Following conditional marketing approval in Europe, the manufacturer of beti-cel priced the therapy at approximately 1.9 million USD, explaining the hypothetical savings in supportive care costs over a period of 50 years, making beti-cel one of the most expensive therapies ever marketed.

At present, the price of beti-cel appears prohibitive for both public and private payers in several countries, signifying the urgent need for a global pricing negotiation structure for this type of medicinal product.

“At the present time, I’m not quite sure what the practical strategies are to reduce cost-related barriers [for these types of therapies],” commented Farzana Sayani, MD, of the department of medicine at the University of University of Pennsylvania, adding that “We still have to see whether insurance companies will pay for these agents.”

In their review, the authors wrote, “Global, transparent and open discussions must be conducted concerning what is and is not acceptable in relation to drug pricing, development costs, manufacturing, and savings associated with sparing prolonged or lifelong supportive care in order to overcome reimbursement issues.”

Until this occurs, new curative gene therapy options may be out of reach for most patients, at least in the short term.


  1. Taher AT, Musallam KM, Cappellini MD. β-thalassemias. N Engl J Med. 2021;384(8):727-743. doi:10.1056/NEJMra2021838
  2. Thuret I, Ruggeri A, Angelucci E, Chabannon C. Hurdles to the adoption of gene therapy as a curative option for transfusion-dependent thalassemia. Stem Cells Transl Med. 2022;11(4):407-414. doi:10.1093/stcltm/szac007
  3. FDA approves first cell-based gene therapy to treat adult and pediatric patients with beta-thalassemia who require regular blood transfusions. News Release. FDA. August 17, 2022. Accessed August 25, 2022.
  4. Hsieh MM, Bonner M, Pierciey FJ, et al. Myelodysplastic syndrome unrelated to lentiviral vector in a patient treated with gene therapy for sickle cell disease. Blood Adv. 2020;4(9):2058-2063. doi:10.1182/bloodadvances.2019001330
  5. Jones RJ, DeBaun MR. Leukemia after gene therapy for sickle cell disease: insertional mutagenesis, busulfan, both, or neither. Blood. 2021;138(11):942-947. doi:10.1182/blood.2021011488