This document addresses gene therapy for beta thalassemia, a genetic disease that involves mutations in the human beta-globin (HBB) gene. These mutations reduce an affected individual’s ability to produce hemoglobin and lead to a shortage of mature red blood cells and a lack of sufficient oxygen. Lentiviral vector gene therapy involves using a modified lentivirus to deliver a functional copy of the beta-globin gene to the patient's cells.

One gene therapy product for beta thalassemia, betibeglogene autotemcel (Zynteglo^®), has been approved by the Food and Drug Administration (FDA). Zynteglo is an autologous hematopoietic stem cell-based gene therapy that requires patients to undergo hematopoietic stem cell (HSC) mobilization followed by apheresis to obtain CD34+ cells for Zynteglo manufacturing, as well as administration of full myeloablative conditioning before infusion of Zynteglo.

Note: Please see the following related documents for additional information:

• CG-MED-68 Therapeutic Apheresis
• CG-MED-90 Chelation Therapy
• MED.00146 Gene Therapy for Sickle Cell Disease
• TRANS.00029 Hematopoietic Stem Cell Transplantation for Genetic Diseases and Aplastic Anemias

Position Statement

Medically Necessary:

A one-time infusion of betibeglogene autotemcel is considered medically necessary in individuals when all of the following criteria are met:

1. Diagnosis of beta thalassemia; and
2. Transfusion-dependent disease (that is, needing at least 8 transfusions or at least 100 ml per kilogram of body weight of packed red cells per year in the previous 2 years); and
3. The individual is a candidate for an allogeneic hematopoietic cell transplantation, but ineligible due the absence of a donor*; and
4. Has no evidence of severe iron overload (for example, T2*-weighted magnetic resonance imaging [MRI] measurements of myocardial iron greater than 10 msec); and
5. No serious concomitant illness (for example, advanced liver disease, uncorrected bleeding disorder, current malignancy, myeloproliferative and/or immunodeficiency disorder, uncontrolled seizure disorder).

*Documentation that a suitable donor has not been identified, for example, a matched related donor or matched (HLA 8/8 or 7/8) unrelated donor.

Investigational and Not Medically Necessary:

Betibeglogene autotemcel is considered investigational and not medically necessary when the criteria above are not met, and for all other indications.