FDA Approves Two Gene Therapies for Sickle Cell Disease

The Food and Drug Administration on Friday announced the approval of the first two gene therapies to treat sickle cell disease (SCD) in the United States: exagamglogene autotemcel (Casgevy, Vertex) and lovotibeglogene autotemcel (Lyfgenia, Bluebird Bio). The agency approved these one-time, single-dose therapies for SCD patients ages 12 and older with a history of vaso-occlusive crises (VOCs).  

Exagamglogene Autotemcel

Exagamglogene autotemcel is the first FDA-approved therapy to employ CRISPR-Cas9 genome editing technology, modifying patients’ hematopoietic stem cells to remove the gene that causes SCD. The modified cells are transplanted back into the patient, where they engraft within the bone marrow. The treatment increases the production of fetal hemoglobin (HbF) to facilitate oxygen delivery and prevent red blood cell (RBC) sickling.

FDA based the approval on findings from an ongoing study of 44 adult and adolescent SCD patients with a history of VOCs. Among 31 patients with sufficient follow-up time to be evaluable, 29 (93.5%) achieved freedom from severe VOC episodes for at least 12 consecutive months during a 24-month follow-up period. All treated patients achieved successful engraftment. None experienced graft failure or graft rejection.

FDA noted that patients receiving exagamglogene autotemcel will be followed in a long-term study to evaluate its safety and effectiveness.

Lovotibeglogene Autotemcel

Lovotibeglogene autotemcel is a cell-based gene therapy that uses a lentiviral vector to add a functional gene that enables production of Hb^AT87Q.  Hb^AT87Q is a therapy-derived hemoglobin that functions similarly to hemoglobin A, which is the normal adult hemoglobin produced in persons not affected by SCD. According to the agency, RBCs containing Hb^AT87Q have a lower risk of sickling and occluding blood flow.

FDA approved lovotibeglogene autotemcel based on data from a single-arm, multicenter study of adult and adolescent patients with SCD and history of vaso-occlusive events (VOEs). Twenty-eight (88%) of 32 patients achieved a complete resolution of VOEs between 6 and 18 months after treatment.

The agency noted that hematologic malignancy has occurred in patients treated with lovotibeglogene autotemcel. The product label includes a black box warning with information regarding this risk. FDA stated that patients should have lifelong monitoring for these malignancies.