The Food and Drug Administration (FDA) has approved Zynteglo® (betibeglogene autotemcel), an autologous hematopoietic stem cell-based gene therapy for the treatment of adult and pediatric patients with beta-thalassemia who require regular red blood cell (RBC) transfusions.

Zynteglo is a one-time gene therapy that works by adding functional copies of a modified form of the β-globin gene into a patient’s own hematopoietic stem cells. The approval was based on data from the phase 3 Northstar-2 (ClinicalTrials.gov Identifier: NCT02906202) and Northstar-3 (ClinicalTrials.gov Identifier: NCT03207009) studies, along with two phase 1/2 studies (ClinicalTrials.gov Identifier: NCT01745120, NCT02151526) and a long-term follow-up study (ClinicalTrials.gov Identifier: NCT02633943). 

The ongoing single-arm, single-dose Northstar-2 and Northstar-3 studies evaluated the efficacy and safety of Zyntelgo administered by intravenous infusion in a total of 41 adult, adolescent, and pediatric patients with beta-thalassemia requiring regular transfusions and both non-β0/β0 and β0/β0 genotypes, with the longest follow-up being 4 years. The primary endpoint for both studies was the proportion of patients who achieved transfusion independence (TI), defined as a weighted average total hemoglobin (Hb) of at least 9g/dL without any packed RBC (pRBC) transfusions for at least 12 months.

Among 22 evaluable patients in the Northstar-2 study, 20 (91%; 95% CI, 71-99) achieved TI with a median (min, max) weighted average Hb during TI of 11.8g/dL (9.7,13.0). All patients who achieved TI were able to maintain TI with a min, max duration of ongoing TI of 15.7+, 39.4+ months. The median (min, max) time to last pRBC transfusion prior to TI was 0.9 (0.5, 2.4) months following Zynteglo infusion. As of last follow-up, 13 of the 20 patients who achieved TI were not on chelation therapy, of which 9 did not restart chelation and 7 received phlebotomy to remove iron.

Among 14 evaluable patients in the Northstar-3 study, 12 (86%; 95% CI, 57-98) achieved TI with a median (min, max) weighted average Hb during TI of 10.20g/dL (9.3,13.7). All patients who achieved TI were able to maintain TI with a min, max duration of ongoing TI of 12.5+, 32.8+ months. The median (min, max) time to last pRBC transfusion prior to TI was 0.8 (0.0, 1.9) months following Zynteglo infusion. As of last follow-up, 7 of the 12 patients who achieved TI were not on chelation therapy, of which 3 did not restart chelation and 1 received phlebotomy to remove iron.

As for safety, the most common non-laboratory adverse reactions (incidence at least 20%) were mucositis, febrile neutropenia, vomiting, pyrexia, alopecia, epistaxis, abdominal pain, musculoskeletal pain, cough, headache, diarrhea, rash, constipation, nausea, decreased appetite, pigmentation disorder, and pruritus. The most common Grade 3 or 4 laboratory abnormalities (incidence greater than 50%) were neutropenia, thrombocytopenia, leukopenia, anemia, and lymphopenia.

“The Cooley’s Anemia Foundation applauds the FDA’s approval of Zynteglo for people with beta‑thalassemia who require regular red blood cell transfusions. The availability of a one-time gene therapy which offers the possibility of transfusion independence opens up new and exciting opportunities for those who are medically eligible to receive this treatment option,” said Craig Butler, National Executive Director, Cooley’s Anemia Foundation.

Zynteglo is supplied in up to four 20mL infusion bags containing a frozen suspension of genetically modified autologous cells, enriched for CD34+ cells. A single dose of Zynteglo for intravenous infusion contains a minimum of 5.0 × 106 CD34+ cells/kg of body weight. 

Zynteglo will be available exclusively at Qualified Treatment Centers which will be carefully selected based on their expertise in relevant areas.

References

  1. bluebird bio Announces FDA Approval of Zynteglo®, the First Gene Therapy for People With Beta-Thalassemia Who Require Regular Red Blood Cell Transfusions. News release. bluebird bio, Inc. Accessed August 17, 2022. https://www.businesswire.com/news/home/20220817005667/en/bluebird-bio-Announces-FDA-Approval-of-ZYNTEGLO%C2%AE-the-First-Gene-Therapy-for-People-with-Beta-Thalassemia-Who-Require-Regular-Red-Blood-Cell-Transfusions
  2. Zynteglo. Package insert. bluebird bio, Inc.; 2022. Accessed August 17, 2022. https://www.bluebirdbio.com/-/media/bluebirdbio/CorporateCOM/Files/Zynteglo/ZYNTEGLO_prescribing_information.pdf