FDA Approval Sought for Beti-Cel to Treat B-Thalassemia Requiring Transfusions

A biologics license application has been submitted to the FDA for betibeglogene autoemcel (beti-cel) gene therapy for the treatment of adult, adolescent, and pediatric patients with B-thalassemia who require regular blood cell transfusions (TDT), across all genotypes, according to a press release by Bluebird Bio, Inc.¹

Beti-cel, a one-time gene therapy, is designed to treat the underlying cause of TDT. This is accomplished by adding functional copies of a modified form of the β-globin gene into a patient’s hematopoietic stem cells. Once this gnee is there, the patient may prodyce HbAT87Q.

The application uses data from 4 studies to argue for approval: the phase 3 HGB-207 study (NCT02906202), HGB-212 (NCT03207009) study, the phase 1/2 HGB-204 (NCT01745120) study, and the HGB-205 study (NCT02151526). Enrollment in the HGB-2087 and HGB-212 studies are complete, and all patients have been treated.

As of March 9, 2021, 41 patients were treated in the HBG-207 and HGB-212 studies. The HBG-207 study had a median follow up of 24.3 months and the HBG-212 had a median follow-up of 23 months. Following treatment, 89% of patients achieved transfusion independence. Independence was maintained for a median of 25 months (range, 12.5-38.5).²

The median gene therapy derived HbAt87Q was stable for approximately 6 months after infusions. At 6-months, it was 8.8 g/dL, 9.2 g/dL at month 9 (n = 34), 8.7 g/dL at year (n = 36), 9.3 g/dL at month 18 (n=29); and 8.9 g/dL at 2-years (n = 26).

In terms of safety, adverse events (AEs) were uncommon and tended to be infusion related. AEs included abdominal pain, hot flush, dyspnea, tachycardia and non-cardiac chest pain and cytopenia’s such as thrombocytopenia, leukopenia and neutropenia.

“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. “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.”

_REFERENCES:

_{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. September 21, 2021. Accessed September 21, 2021. https://bit.ly/3zD92Ig.}

_{2. Betibeglogene autotemcel (beti-cel) one-time gene therapy for β-thalassemia continues to demonstrate durable efficacy across pediatric and adult patient populations and all genotypes in data presented at EHA2021 virtual. News release. June 11, 2021. Accessed September 21, 2021. https://bit.ly/3kymrgq.}