RARE Daily

FDA Advisory Committee Unanimously Supports Bluebird’s Beti-cel Gene Therapy for Beta-thalassemia

June 13, 2022

The U.S. Food and Drug Administration’s Cellular, Tissue, and Gene Therapies Advisory Committee unanimously supported approval of the company’s gene therapy beti-cel for the treatment of people with beta-thalassemia who require regular red blood cell transfusions.

Photo: Andrew Obenshain, CEO of Bluebird Bio

Photo: Andrew Obenshain, CEO of Bluebird Bio

The vote comes one day after endorsing approval of Bluebird bio’s gene therapy eli-cel for the treatment children with the rare neurodegenerative condition CALD.

The advisory committee voted unanimously that the benefits of beti-cel outweigh the risks for the treatment of subjects with transfusion-dependent beta-thalassemia.

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 two to five 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.

“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, CEO of 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.”

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 Northstar-2 and Northstar-3, the phase 1/2 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.

Beti-cel is a one-time gene therapy custom-designed to treat the underlying cause of beta-thalassemia in patients who require regular red blood cell transfusions. Beti-cel adds functional copies of a modified form of the beta-globin gene (βA-T87Q-globin gene) into a patient’s own hematopoietic (blood) stem cells (HSCs) to correct the deficiency of adult hemoglobin that is the hallmark of beta-thalassemia. Once a patient has the βA-T87Q-globin gene, they have the potential to produce beti-cel-derived adult hemoglobin at levels that may eliminate the need for transfusions. As of the data cutoff date (August 2021), 89 percent (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.

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.

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.

Author: Rare Daily Staff

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