beti-cel BLA Submitted for β-Thalassemia


The news comes after another of bluebird bio’s programs, eli-cel, was placed on clinical hold.

bluebird bio has submitted a biologics license application (BLA) to the FDA for their gene therapy betibeglogene autotemcel (beti-cel) for the potential treatment of patients with β-thalassemia who require regular red blood cell transfusions.1

The company has submitted the BLA based on data from 2 phase 3 studies (NCT03207009 and NCT02906202) evaluating beti-cel across all phenotypes as well as a previous phase 1/2 study (NCT01745120). The studies have enrolled 63 pediatric, adolescent, and adult patients treated with beti-cel, with all patients completing at least 5 years and at most 7 years of follow up. The data from these studies comprise over 220 patient years with beti-cel. 

"With this submission, we are one step closer to bringing a potentially transformative gene therapy to people living with TDT and their families," said Andrew Obenshain, president, severe genetic diseases, bluebird bio, in a statement.1 "At bluebird bio, we have a deep understanding of gene therapies, built over a decade of research and development in severe genetic diseases. We look forward to working with the FDA on its review of this BLA as we realize the promise that one-time gene therapies hold for patients."

Results from the phase 3 studies showed that 89% (32/36) of evaluable patients across all criteria achieved transfusion independence with beti-cel treatment. Both studies are ongoing, although enrollment has completed and all patients have been treated. bluebird bio is also conducting a long-term follow-up study (NCT02633943) for all patients in programs treated with lentiviral vectors.

READ MORE: Beti-Cel Withdrawn From Germany, bluebird Reduces Workforce

Treatment-related adverse events (AEs) were uncommon and included infusion-related reactions, cytopenias, and extremity pain following treatment. A serious AE possibly related to treatment, thrombocytopenia, did occur.

beti-cel was previously granted orphan drug designation and breakthrough therapy designation for the treatment of transfusion-dependent β-thalassemia. If the BLA is accepted and approved by the FDA, beti-cel will be the first hematopoietic stem cell ex-vivo gene therapy approved in the US.

beti-cel uses the BB305 lentiviral vector to transfer functional copies of a modified form of the β-globin gene to patients. The FDA previously put a number of bluebird bio’s studies using this vector on hold in February 2021 following the diagnosis of acute myeloid leukemia (AML) in a patient who received the BB305-based gene therapy bb1111 approximately 6 years ago in a phase 1/2 study.2 Another Suspected Unexpected Serious Adverse Reactions (SUSARs) of myelodysplastic syndrome (MDS) was also reported.

The clinical holds were lifted in June 2021 after the company demonstrated that the lentiviral vector was not associated with cancer in their β-thalassemia and sickle cell disease trials. No disruption in gene expression or regulation was found in these patients. However, another of bluebird’s therapies that use the lentiviral vector, elivaldogene autotemcel (eli-cel), was put on clinical hold by the FDA in August 2021 following the SUSAR of MDS thought to be mediated by the vector.3 The same therapy was approved in Europe as Skysona in July 2021.

“Our hearts go out to this patient and his family, who are dealing with a challenging diagnosis,” Nick Leschly, president and chief executive officer, bluebird, said in a company update at that time.3 “Given what we know, we remain confident that eli-cel can offer hope for patients and families impacted by this devastating disease who have very few treatment options. We are committed to working with regulators and physicians in order to resolve this hold as soon as possible and bring this important therapy to patients in need.”

1. bluebird bio submits biologics license application (BLA) to FDA for betibeglogene autotemcel (beti-cel) gene therapy for patients with β-thalassemia who require regular red blood cell transfusions. News release. bluebird bio. September 21, 2021.
2. bluebird bio announces the lifting of FDA clinical hold for sickle cell disease and β-thalassemia studies. News release. bluebird bio. June 7, 2021.
3. bluebird bio reports second quarter financial results and provides operational update. News release. bluebird bio. August 9, 2021.
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