The gene therapy betibeglogene autotemcel, sold under the brand name LentiGlobin, was shown to be safe and effective in a subset of patients with sickle cell disease in the HGB-206 group C study ( Identifier: NCT02140554), according to updated results presented at the 2021 American Society of Pediatric Hematology/Oncology (ASPHO) meeting.

The ongoing phase 1/2 HGB-206 study is investigating LentiGlobin gene therapy, which uses a modified human β-globin gene which produces gene therapy-derived antisickling hemoglobin (HbAT87Q). This study sought to assess the safety and efficacy of this therapy in the patients included in group C of the larger trial for up to 2 years of follow-up.

Patients with sickle cell disease and recurrent severe vaso-occlusive events, including acute episodes of pain and acute chest syndrome (ACS), were enrolled in this analysis. Patients were monitored for their hemoglobin levels, hemolysis markers, sickle cell disease-related outcomes, and adverse events (AEs).

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A total of 40 patients in group C (mean age, 23.5 years; range, 12-38), including 9 adolescent patients, were included in the study. A total of 25 patients were treated with LentiGlobin. All patients were able to stop red blood cell transfusions by 90 days post-treatment, and hemolysis markers trended toward normalization in 25 patients.

For 16 evaluable patients, their total hemoglobin at time of last visit was 11.5 (9.6-16.2) g/dL, with HbAT87Q contribution of 5.2 (2.7-9.4) g/dL, hemoglobin S contribution of 6.1 (4.9-7.8) g/dL, and median hemoglobin S at ≤60% of total hemoglobin.

In 14 patients with a history of vaso-occlusive crisis (VOC) or ACS, the annualized VOC and ACS rate was 4.0 (2.0-14.0) in the 2 years prior to treatment. After treatment, no ACS or serious VOCs were observed in these patients.

The most common nonhematologic grade ≥3 AEs included stomatitis (15 patients) and febrile neutropenia (11 patients). Serious AEs included nausea, opioid withdrawal syndrome, and vomiting (2 patients for each). A total of 3 patients had a nonserious AE as a result of LentiGlobin therapy. There was no graft failure, vector-mediated replication-competent lentivirus, or clonal dominance observed in the study.

This safety profile was consistent with single-agent busulfan conditioning and underlying sickle cell disease. Complete resolution of VOC and ACS was observed in almost all of the patients. Hemoglobin S expression was lowered, and total hemoglobin increased as a result of LentiGlobin therapy.

Disclosure: This clinical trial was supported by bluebird bio. Please see the original reference for a full list of authors’ disclosures.


Kwiatkowski J, Thompson A, Walters M, et al. Updated results from the HGB-206 group C study of LentiGlobin for sickle cell disease gene therapy. Paper presented at: 2021 American Society of Pediatric Hematology/Oncology virtual meeting; April 21-23, 2021.