bluebird bio Shares Promising Long-Term Data on LYFGENIA™ Gene Therapy for Sickle Cell Disease at 66th ASH Meeting

SOMERVILLE, Mass.--bluebird bio, Inc. (Nasdaq: BLUE) has released new and updated data on LYFGENIA™ (lovotibeglogene autotemcel, or lovo-cel) gene therapy for patients with sickle cell disease who have experienced vaso-occlusive events (VOEs). This information will be shared during the 66th American Society of Hematology (ASH) Annual Meeting and Exposition on December 8, 2024. By July 2024, 70 patients had been treated under the lovo-cel clinical development program, with some patients having over nine years of follow-up.

Richard Colvin, M.D., Ph.D., the chief medical officer at bluebird bio, emphasized that the long-term benefits of LYFGENIA are consistent across various sub-populations, including those with overt stroke, which is a unique aspect of the program compared to other gene therapies for sickle cell disease. The data presented at ASH highlights LYFGENIA as the leading gene therapy for sickle cell disease, with the highest number of patients treated, the longest follow-up period, and a broad range of clinical presentations evaluated.

The updated efficacy data underscore the sustained impact of lovo-cel on reducing VOE burden and improving hematologic markers. Specifically, 58 patients treated under the HGB-206 Group C and HGB-210 studies received lovo-cel after enhancements to manufacturing and treatment protocols. The median follow-up time was 47.7 months, with 15 participants having more than five years of follow-up.

Stacy Rifkin-Zenenberg, DO, from Hackensack Meridian Health, commented on the durability of lovo-cel's clinical benefits for sickle cell disease patients. She noted that the extensive patient data and follow-up have allowed for a detailed examination of the pharmacology and mechanism of LVV gene therapy, supporting lovo-cel's potential to address the underlying cause of sickle cell disease permanently. By the cutoff date in July 2024, all patients maintained stable production of anti-sickling adult hemoglobin, with significant reductions in VOEs and severe vaso-occlusive events (sVOEs). Specifically, 94.7% of evaluable patients achieved complete resolution of severe VOEs, and 86.8% achieved complete resolution of VOEs.

The safety profile of the lovo-cel treatment regimen was generally in line with the underlying sickle cell disease and known effects of myeloablative conditioning. There were no cases of graft failure, graft-versus-host disease (GVHD), vector-related complications, or insertional oncogenesis.

Additionally, data on patients with a history of overt stroke indicated no recurrence of stroke following lovo-cel treatment, even up to nine years post-treatment. Jennifer Jaroscak, MD, from the Medical University of South Carolina, highlighted that no participants with a history of overt or silent stroke experienced recurrent strokes post-treatment, despite discontinuing transfusions. This result is notable given that these patients are at high risk for subsequent strokes and transfusions alone offer limited protection.

Overt ischemic stroke, a severe complication of sickle cell disease, typically requires lifelong transfusions or allogeneic hematopoietic stem cell transplantation, both of which carry significant risks. The analysis also included patients with evidence of silent stroke, showing no recurrence of overt or silent strokes among those with follow-up MRIs. Safety findings for participants with a history of stroke were consistent with the overall treatment group.

LYFGENIA™ is a one-time ex-vivo lentiviral vector gene therapy approved for treating patients aged 12 years or older with sickle cell disease and a history of VOEs. The therapy works by adding a functional β-globin gene to patients' hematopoietic stem and progenitor cells, enabling the production of anti-sickling adult hemoglobin. The HGB-206 Phase 1/2 study is complete, and the HGB-210 Phase 3 study is ongoing, with a long-term safety and efficacy follow-up study (LTF-307) also in progress.

LYFGENIA has demonstrated significant promise in reducing the frequency and severity of VOEs and improving overall hematologic health in sickle cell disease patients. The extensive clinical data and long-term follow-up continue to support its potential as a transformative therapy for this condition.