New data from lovotibeglogene autotemcel gene therapy for sickle cell disease presented at 64th ASH annual meeting.- bluebird bio.

The updated data demonstrate sustained treatment effect in patients treated lovotibeglogene autotemcel (lovo-cel) gene therapies through additional follow-up. Case studies of two patients diagnosed with persistent anemia following lovo-cel treatment were also presented. The ASH Annual Meeting is taking place December 10-13, 2022, in New Orleans and virtually.

New analyses deepen understanding of safety profile for lovo-cel gene therapy in sickle cell disease. Case studies presented at ASH provided detail on investigations into two cases of persistent anemia observed in an adult and pediatric patient in Group C, the pivotal cohort of the HGB-206 study of lovo-cel; data were as of August 2022.

Both patients had two alpha-globin gene deletions (alpha 3.7/alpha 3.7), also known as alpha-thalassemia trait, and notably are the only patients in the study with this specific genotype. Integration site analysis and next-generation sequencing showed no evidence of clonal processes (vector-related or otherwise) and findings are not consistent with an emerging hematologic malignancy. Clinical investigations presented suggest that the alpha-thalassemia trait likely contributed to anemia after lovo-cel infusion. Following these cases, this genotype was added to exclusion criteria for ongoing studies.

“An in-depth analysis of two cases of ineffective erythropoiesis with persistent anemia following lovo-cel treatment reassure that these cases do not have clonal evolution or an emerging malignancy. The working hypothesis is that the anemia is attributable to alpha-thalassemia trait with robust HbAT87Q production,” said Mark C. Walters, M.D., Jordan Family Director, BMT Program, UCSF Benioff Children’s Hospital Oakland, Oakland, CA.

Updated data from the HGB-206 parent study presented at ASH showed 96% (31/32) of patients treated in Group C experienced complete resolution of severe vaso-occlusive events (sVOE) through 24 months of follow-up; a single sVOE was observed in the adult patient experiencing persistent anemia. As of last follow-up of 24 months, the adult patient is transfusion dependent and experiencing intermittent exacerbations of chronic pain, while the pediatric patient has not required transfusions and remains clinically well.In Group C of HGB-206, the safety profile of the lovo-cel treatment regimen from Day 1 to Month 24 generally reflects the known side effects of busulfan conditioning regimen, and AEs commonly seen in the population being evaluated. The most frequently reported serious AEs after lovo-cel infusion in two or more HGB-206 Group C patients were pain (11.1%), abdominal pain, anemia, drug withdrawal syndrome (opiate), nausea, suicidal ideation, and vomiting (5.6% each). There have been no cases of veno-occlusive liver disease, graft failure, insertional oncogenesis or replication-competent lentivirus.

The data were presented in Oral #11: lovo-cel (bb1111) Gene Therapy for Sickle Cell Disease: Updated Clinical Results and Investigations into Two Cases of Anemia from Group C of the Phase 1/II HGB-206 Study?.Studies evaluating lovo-cel in sickle cell disease represent the most mature sickle cell disease gene therapy dataset in the industry, with the longest available follow-up data. As of August 2022, 50 patients have been treated with lovo-cel across the HGB-205 (n=3), HGB-206 (n=45) and HGB-210 (n=2) clinical studies, with up to 7 years of patient follow-up (median: 37.7 months) representing 176.5 total patient-years of data.

bluebird bio remains on track to submit a biologics license application (BLA) for lovo-cel in Q1 2023.