FDA Advisory Committee Unanimously Supports beti-cel Gene Therapy for People with beta-thalassemia Who Require Regular Red Blood Cell Transfusions

Current standard of care relies on regular red blood cell transfusions and iron management that carry the risk of progressive multi-organ damage and increased risk of morbidity and mortality

If approved, beti-cel will be the first potentially curative gene therapy option for people with beta-thalassemia who require regular red blood cell transfusions and the first ex-vivo LVV gene therapy available in the U.S.

PDUFA goal date is set for August 19, 2022

bluebird bio, Inc. (Nasdaq: BLUE) today announced the outcome of the U.S. Food and Drug Administration’s (FDA) Cellular, Tissue, and Gene Therapies Advisory Committee (CTGTAC) discussion of betibeglogene autotemcel (beti-cel) for the treatment of people with beta-thalassemia who require regular red blood cell (RBC) transfusions.

On the question “Do the benefits of beti-cel outweigh the risks for the treatment of subjects with transfusion-dependent beta-thalassemia?” the CTGTAC voted 13 (yes) to 0 (no).

“Despite advances in care, people living with the most severe form of beta-thalassemia still require frequent transfusions of healthy red blood cells to survive, tethering them to the healthcare system for life and increasing their risk for severe complications and early death,” said Andrew Obenshain, chief executive officer, bluebird bio. “Today’s advisory committee recommendation is recognition of the substantial body of clinical data that support beti-cel as a potentially curative treatment option for these patients. We are grateful to the members of the beta-thalassemia community who contributed to today’s discussion and remain committed to working with the FDA as it completes its review of the beti-cel Biologics License Application.”

Beta-thalassemia is a rare genetic blood disease caused by mutations in the beta-globin gene and is characterized by significantly reduced or absent adult hemoglobin production. Patients with the most severe form experience severe anemia and lifelong dependence on red blood cell transfusions, a lengthy process that patients typically undergo every 2-5 weeks. Despite advances in treatment and improved transfusion techniques, transfusions only temporarily address symptoms of anemia and people with beta-thalassemia who require regular transfusions have an increased risk for morbidity and mortality due to treatment- and disease-related iron overload and its complications. Data from the Cooley’s Anemia Foundation indicate that the median age of death of U.S. transfusion-dependent beta-thalassemia patients who died during the last decade was just 37 years.

The advisory committee’s recommendation is based on the Biologics License Application (BLA) currently under priority review by the FDA with a decision goal date set for August 19, 2022. The BLA is based on data from bluebird bio’s Phase 3 studies HGB-207 (Northstar-2) and HGB-212 (Northstar-3), the Phase 1/2 HGB-204 (Northstar) and HGB-205 studies, and the long-term follow-up study LTF-303 as of March 2021. Additionally, as of the latest data cutoff date (August 2021), data from bluebird bio’s clinical development program represent 240 patient-years of experience with beti-cel and the longest available follow-up data in beta-thalassemia patients requiring regular RBC transfusions treated with a one-time gene therapy.

On June 9, the CTGTAC unanimously endorsed eli-cel, an investigational LVV gene therapy for the treatment of cerebral adrenoleukodystrophy, in a 15 to 0 vote.

“We are pleased that the advisory committee recognized the significant potential of LVV gene therapies to address severe unmet medical needs – demonstrated over more than a decade of research and more than 500 patient-years of experience – as well as the urgent need for improved treatments,” said Anne-Virginie Eggimann, chief regulatory officer, bluebird bio. “We thank the FDA for convening this discussion on bluebird bio’s LVV gene therapies and look forward to the completion of the Agency’s review.”

In addition to granting the beti-cel BLA priority review, the FDA previously granted beti-cel Orphan Drug status and Breakthrough Therapy designation. bluebird bio is eligible to receive a priority review voucher upon potential approval of beti-cel.

About beta-thalassemia

Beta-thalassemia is a severe genetic blood disease caused by mutations in the beta-globin gene and is characterized by significantly reduced or absent adult hemoglobin production. This can result in severe anemia and lifelong dependence on red blood cell (RBC) transfusions. Patients who require regular RBC transfusions to maintain adequate Hb levels typically undergo the 4-7-hour process every 2-5 weeks. While transfusions temporarily relieve symptoms associated with severe anemia, including fatigue, weakness, and shortness of breath, they do not address the underlying genetic cause of beta-thalassemia and can lead to unavoidable iron overload and serious complications, including progressive multi-organ damage and organ failure. Iron overload resulting from beta-thalassemia or ongoing RBC transfusions requires chronic treatment with chelation therapy; even with chelation therapy, some patients remain significantly iron overloaded, and only 63% of patients are adherent, due in part to tolerability issues. Despite advances in treatment and improved transfusion techniques, people with beta-thalassemia who require regular transfusions have an increased risk for morbidity and mortality.

About betibeglogene autotemcel (beti-cel)

betibeglogene autotemcel (beti-cel) (pronounced BEH tee cell) is a one-time gene therapy custom-designed to treat the underlying cause of beta-thalassemia in patients who require regular red blood cell (RBC) transfusions. beti-cel adds functional copies of a modified form of the beta-globin gene (β^A-T87Q-globin gene) into a patient’s own hematopoietic (blood) stem cells (HSCs) in order to correct the deficiency of adult hemoglobin that is the hallmark of beta-thalassemia. Once a patient has the β^A-T87Q-globin gene, they have the potential to produce beti-cel-derived adult hemoglobin (HbA^T87Q) at levels that may eliminate the need for transfusions. As of the data cutoff date (August 2021), 89% (34/38) of evaluable patients in Phase 3 beti-cel studies achieved transfusion independence, which is defined as no longer needing RBC transfusions for at least 12 months while maintaining a weighted average Hb of at least 9 g/dL. These results were observed across all ages and genotypes, including pediatric patients as young as four years of age and those with the most severe (β⁰/β⁰) genotypes.

beti-cel is manufactured using the BB305 lentiviral vector (LVV), a third-generation, self-inactivating LVV that has been studied for more than a decade across two therapeutic areas.

Adverse reactions considered related to beti-cel were infrequent and consisted primarily of non-serious infusion-related reactions that occurred on the day of infusion (e.g., abdominal pain, hot flush, dyspnea, tachycardia and non-cardiac chest pain) and cytopenias (e.g., thrombocytopenia, leukopenia and neutropenia). One of these adverse reactions was a serious adverse event (SAE) of thrombocytopenia considered possibly related to beti-cel and has resolved.

The majority of AEs and SAEs in the beti-cel clinical development program were unrelated to beti-cel and largely reflect the known side effects of HSC collection and busulfan conditioning regimen (including several SAEs of veno-occlusive disease that resolved with treatment).

The Phase 3 Northstar-2 (HGB-207) and Northstar-3 (HGB-212) studies evaluating beti-cel are ongoing; enrollment is complete, and all patients have been treated. bluebird bio is also conducting a long-term follow-up study, LTF-303, to monitor safety and efficacy for people who have participated in bluebird bio-sponsored beti-cel clinical studies through 15 years post-treatment.

About bluebird bio, Inc.

bluebird bio is pursuing curative gene therapies to give patients and their families more bluebird days.

With a dedicated focus on severe genetic diseases, bluebird has industry-leading clinical and research programs for sickle cell disease, beta-thalassemia and cerebral adrenoleukodystrophy and is advancing research to apply new technologies to these and other diseases. We custom design each of our therapies to address the underlying cause of disease and have developed in-depth and effective analytical methods to understand the safety of our lentiviral vector technologies and drive the field of gene therapy forward.

Founded in 2010, bluebird has the largest and deepest ex-vivo gene therapy data set in the world—setting the standard for industry. Today, bluebird continues to forge new paths, combining our real-world experience with a deep commitment to patient communities and a people-centric culture that attracts and grows a diverse flock of dedicated birds. ​

For more information, visit bluebirdbio.com or follow us on social media at @bluebirdbio, LinkedIn, Instagram and YouTube.

bluebird bio is a trademark of bluebird bio, Inc.

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