Zynteglo (betibeglogene autotemcel)

The first cell-based gene therapy approved for beta-thalassemia. Casgevy (exagamglogene autotemcel), which uses CRISPR gene editing to raise fetal hemoglobin, was approved for transfusion-dependent beta-thalassemia in January 2024; no trial has compared the 2 head to head.

In beta-thalassemia, changes in the beta-globin gene mean the body makes too little or no beta-globin, one of the 2 kinds of protein chains in adult hemoglobin. Leftover alpha chains damage developing red blood cells, causing severe anemia and the need for regular transfusions. To make Zynteglo, doctors collect the patient's blood-forming stem cells, and a lab adds working copies of a modified beta-globin gene, called beta-A-T87Q, using a lentiviral vector (BB305) that switches the gene on only in cells that become red blood cells. After busulfan clears the bone marrow, the corrected cells are infused back, settle in the marrow and make red blood cells containing a working hemoglobin called HbAT87Q. In the studies, this new hemoglobin rose steadily and leveled off about 6 months after infusion.

Zynteglo has no boxed warning and no contraindications. Its studies had no placebo group, and many side effects come from the busulfan chemotherapy. Among 41 treated patients in the first 24 months, the most common were mucositis, painful sores in the mouth and gut (95%), febrile neutropenia (51%), vomiting (49%), fever (49%), hair loss (44%), nosebleeds (42%), abdominal pain (39%), muscle and bone pain (37%), cough (34%), headache (29%), diarrhea (27%), rash (27%), constipation (24%), nausea (24%), decreased appetite (24%), skin color changes (24%) and itching (22%). Severe drops in neutrophils, platelets and white cells occurred in all patients and severe anemia in 95%, as expected after conditioning. Serious side effects occurred in 37% of patients, and no patients died^[1]. The label warns about slow platelet recovery, with a median of 46 days and 15% of patients still having severely low platelets on or after day 100, which raises bleeding risk. It also warns about possible failure of the new cells to take, a potential risk of blood cancer because the vector inserts into DNA, and allergic reactions to the DMSO preservative. Serious liver veno-occlusive disease occurred in 3 patients (7%), 2 of whom had not received preventive treatment, and all recovered with defibrotide. Treated patients can test falsely positive on PCR tests for HIV^[1].

Pick your insurance to see which help fits. Drugmaker copay cards can't be used with Medicare, Medicaid or TRICARE; charity funds are the usual route there.

More ways to get help paying for treatment →

Approved for adults and children with beta-thalassemia who need regular red blood cell transfusions, when a stem cell transplant is judged appropriate. Study patients were 4 to 34 years old; safety and effectiveness under age 4 have not been established, and it has not been studied over age 65. The studies excluded people with severe iron overload in the heart or advanced liver disease such as cirrhosis or bridging fibrosis. A negative HIV test is required before cells are collected, and kidney and liver function are checked first.

Source: Genetix CARES patient support

Access program details are provided for informational purposes and may vary based on insurance coverage, geographic location, and individual circumstances. Confirm current eligibility directly with the manufacturer or your specialty pharmacy.

The FDA based approval on 2 phase 3, single-arm studies in 41 patients aged 4 to 34 who needed at least 100 mL/kg of red cells or at least 8 transfusions a year. HGB-207 (NCT02906202) treated 23 patients without the beta-zero/beta-zero genotype, and 20 of 22 evaluable patients (91%) reached transfusion independence, meaning no transfusions for at least 12 months with an average hemoglobin of 9 g/dL or more, at a median hemoglobin of 11.8 g/dL. HGB-212 (NCT03207009) treated 18 patients, 12 with the beta-zero/beta-zero genotype, and 12 of 14 evaluable patients (86%) reached transfusion independence, at a median hemoglobin of 10.2 g/dL. Overall, 32 of 36 evaluable patients (89%) became transfusion independent, and all of them stayed that way through the latest follow-up, which reached more than 39 months. The 4 who did not had cuts in transfusion volume ranging from 3% to 92%^[1][10][11]. Patients are followed for 13 more years in the long-term study LTF-303 (NCT02633943)^[1][12].

The therapy was developed by bluebird bio under the name LentiGlobin BB305^[10]. It received Fast Track designation on January 31, 2013, Orphan Drug designation on March 18, 2013, Breakthrough Therapy designation on January 29, 2015 and Rare Pediatric Disease designation on November 30, 2018. The final part of the rolling application arrived on September 20, 2021, an FDA advisory committee met on June 9 and 10, 2022, and the FDA approved Zynteglo on August 17, 2022 with a rare pediatric disease priority review voucher^[3][2]. At launch, bluebird set the wholesale acquisition cost at $2.8 million and offered insurers an outcomes-based agreement refunding up to 80% of the cost if a patient does not achieve and keep transfusion independence for up to 2 years after infusion^[5]. After a sale to new private owners announced in June 2025, the company renamed itself Genetix Biotherapeutics on September 18, 2025^[6].

Other US options for transfusion-dependent beta-thalassemia include ongoing transfusions with iron chelation, donor stem cell transplant for some patients, and Casgevy, a gene-edited cell therapy approved for this use in January 2024.