FDA Accepts Beti-Cel BLA for β-thalassemia


The investigational gene therapy, which will receive priority review, has a PDUFA date of May 20, 2022.

The FDA has accepted bluebird bio’s Biologics License Application (BLA) for betibeglogene autotemcel (beti-cel) for the potential treatment of β-thalassemia. The gene therapy, which will receive priority review, has a PDUFA date of May 20, 2022.1

“The FDA’s acceptance of our BLA for beti-cel brings us one step closer to potentially providing a one-time treatment that can address the underlying cause of β-thalassemia and offer patients freedom from regular transfusions,” said Andrew Obenshain, chief executive officer, bluebird bio, in a statement.1 “It’s also a critical milestone for bluebird bio as an independent severe genetic disease company. We are moving forward with great discipline and exceptional care to deliver on our commitments to patients and achieve our near-term goal of launching three first-in-class gene therapies in the US”

The FDA accepted the BLA for beti-cel based on data from the phase 3 studies HGB-207 (Northstar-2; NCT02906202) and HGB-212 (Northstar-3; NCT03207009), the Phase 1/2 HGB-204 (Northstar; NCT01745120) and HGB-205 (NCT02151526) studies, and the long-term follow-up study LTF-303 (NCT02633943).

As of Match 9, 2021, a total of 63 pediatric, adolescent, and adult patients have been dosed with beti-cel with a combined 220 patient-years of experience. Long-term efficacy and safety data from more than 7 years in 2 patients has been collected. Updated data through August 2021 will be presented at the 63rd American Society of Hematology (ASH) Annual Meeting and Exposition, December 11-14, 2021.

READ MORE: Eli-cel Gene Therapy for Early CALD to Be Withdrawn From EU, UK

“For too long, people with β-thalassemia who rely on regular transfusions have had to live with extraordinary burdens associated with their disease. beti-cel works uniquely to help patients produce adult hemoglobin at normal or near-normal levels, which can eliminate their need for chronic transfusions and chelation that only temporarily relieve the symptoms of anemia and are associated with serious health risks and reduced quality of life,” Anne-Virginie Eggimann, chief regulatory officer, bluebird bio, added to the statement.1 “This BLA acceptance represents the culmination of contributions from many, including the patients involved in the clinical program, their caregivers, and the study investigators. We look forward to working closely with the FDA to bring this treatment to patients in need.”

Beti-cel uses the BB305 lentiviral vector to add functional copies of an engineered β-globin gene (βA-T87Q-globin gene) to a patient’s hematopoietic stem cells. The therapy demonstrated a positive effect in the phase 3 studies, with 89% (32/36) of evaluable patients across all ages and genotypes achieving transfusion independence. The phase 3 studies as well as the long-term follow-up study are ongoing.

Adverse events (AEs) related to beti-cel included infusion-related reactions such as abdominal pain, hot flush, dyspnea, tachycardia and non-cardiac chest pain, and cytopenias. Extremity pain after treatment also occurred. Most AEs and serious AEs were unrelated to treatment, although a serious AE of thrombocytopenia was considered possibly related to beti-cel and has since resolved.

The FDA previously put a number of bluebird bio’s studies using this vector, including the beti-cel program, on hold in February 2021 following the diagnosis of acute myeloid leukemia in a patient who received the BB305-based gene therapy bb1111 approximately 6 years ago in a phase 1/2 study in sickle cell disease.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.

The push forward in the US market follows bluebird's withdrawal from the European Union (EU) and United Kingdom (UK) earlier this year, including the withdrawal of its EU marketing authorization and UK filing for Skysona (elivaldogene autotemcel; eli-cel) for the treatment of cerebral adrenoleukodystrophy (CALD) as well as Zynteglo (betibeglogene autotemcel; beti-cel) for the treatment of β-thalassemia from both markets by early 2022 following ongoing challenges with regulators over pricing and marketing disputes.

1. bluebird bio Announces FDA Priority Review of Biologics License Application for beti-cel Gene Therapy for Patients with β-thalassemia Who Require Regular Red Blood Cell Transfusions. News release. bluebird bio. November 22, 2021. https://www.biospace.com/article/releases/bluebird-bio-announces-fda-priority-review-of-biologics-license-application-for-beti-cel-gene-therapy-for-patients-with-%CE%B2-thalassemia-who-require-regular-red-blood-cell-transfusions/
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. https://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-announces-lifting-fda-clinical-hold-sickle-cell
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