Long-term data for betibeglogene autotemcel shows patients achieve transfusion independence and remain free from transfusions up to six years.- bluebird bio Inc.

bluebird bio, Inc. presented updated long-term efficacy and safety results reflecting up to six years of data for betibeglogene autotemcel gene therapy (beti-cel; formerly LentiGlobin for beta-thalassemia) in patients with transfusion-dependent beta-thalassemia (TDT). The company also presented results for pediatric patients in the Phase III HGB-207 (Northstar-2) and HGB-212 (Northstar-3) studies . These data were presented at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, taking place virtually from December 5-8, 2020. Long-term follow-up study LTF-303: Efficacy : After participating in and completing the two years of follow-up in either Phase 1/II studies (HGB-204, HGB-205), or in one of the Phase III studies (HGB-207, HGB-212), patients treated with beti-cel were invited to enroll in the 13-year long-term follow-up study, LTF-303 . As of March 3, 2020, 32 patients were enrolled in LTF-303 (22 treated in Phase 1/II studies, 10 treated in Phase III studies) with a median post-infusion follow-up of 49.1 months (min-max: 23.3 – 71.8 months). Of the 32 patients enrolled in LTF-303, TI was achieved in 14/22 (64%) patients treated in Phase 1/II and in 9/10 (90%) patients treated in Phase III. All patients who achieved TI remained free from transfusions [median duration of ongoing TI is 39.4 months (min-max: 19.4 – 69.4 months)]. Weighted average Hb in patients who achieved TI in the Phase 1/II was 10.4 (min-max: 9.4 – 13.3) g/dL and 12.5 (min-max: 11.9 – 13.5) g/dL in patients who achieved TI in the Phase III studies. Median gene therapy-derived hemoglobin (HbAT87Q) in all patients treated in the Phase 1/II studies was stable over time: 6.4 (min-max: 0.5 – 10.1) g/dL at Month 24 (n=22), 6.7 (min-max: 0.4 – 10.1) g/dL at Month 36 (n=22), 6.6 (min-max: 0.5 – 10.7) g/dL at Month 48 (n=22), and 7.1 (min-max: 2.8 – 11.2) g/dL at Month 60 (n=10). Median HbAT87Q at Month 24 in all patients treated in the Phase III studies was 9.5 (min-max: 0.9 – 12.4) g/dL (n=10). Following an initial increase in liver iron concentration (LIC) after infusion, LIC in patients who achieved TI decreased, particularly in patients with a high iron burden at baseline. Patients with severe (LIC greater than 15 mg/g, n=2) and significant (LIC greater than 7 – 15 mg/g, n=5) iron burden at baseline had a median reduction of 59% and 38%, respectively, from baseline to Month 48. Prior to beti-cel infusion, all patients were on iron chelation, which is needed to reduce excess iron caused by chronic blood transfusions. Of the 23 patients who achieved TI following treatment with beti-cel, the majority (65%, n=15) discontinued iron chelation and 30% (7/23) were able to receive phlebotomy (blood removal), which is a preferred method for iron reduction. Long-term follow-up study LTF-303: Safety : In LTF-303, there were no deaths, no graft-versus-host disease (GVHD), and no cases of replication-competent lentivirus, insertional oncogenesis or clonal dominance were observed. No drug-related adverse events (AEs) were reported greater than 2 years post-infusion. Serious AEs during LTF-303 unrelated to beti-cel included gonadotropic insufficiency, ectopic pregnancy, gall bladder wall thickening/polyp, bacteremia, neutropenia and major depression (n=1 for each). Phase III Pediatric Patients: Efficacy : As of March 3, 2020, 24 pediatric patients ( less than 12 years: n=13; greater than 12 to less than 18 years: n=11) were treated and had a median follow-up of 15.5 months (min-max: 1.1 – 29.5 months) in Phase III HGB-207 (Northstar-2) and HGB-212 (Northstar-3) studies. In these Phase III studies, the median age at which the children under 12 received their first transfusion was 11 months of age; for the adolescents between the ages of 12 and 18, the median was eight months of age. Following treatment with beti-cel, 87% (13/15) of evaluable patients under the age of 18 years, including four patients under age 12, achieved TI. As of March 3, 2020, these patients continue to be free of transfusions for a median duration of 14.9 months (min-max: 12.2 – 21.6 months), with median weighted average total Hb levels of 11.3 g/dL (min-max: 9.4 – 12.8 g/dL). Phase III Pediatric Patients: Safety: Drug-related AEs in pediatric patients during the HGB-207 and HGB-212 trials were non-serious and included tachycardia (Grade 1, n=1) and abdominal pain (Grade 1, n=2) on the day of infusion, and Grade 3 thrombocytopenia in one patient post-infusion. There were no deaths, no GVHD, no graft failures, and no cases of replication-competent lentivirus, insertional oncogenesis or clonal dominance were observed. Post-infusion non-hematologic Grade greater than 3 AEs in greater than patients < 18 years of age (N=24) included stomatitis (n=14), febrile neutropenia (n=12), decreased appetite (n=5), epistaxis (n=4), alanine aminotransferase increase (n=3), hypoxia (n=3) and pyrexia (n=3). The presentations are now available on demand on the ASH conference website:.