MODERATE IMPACT – After a second day of presentations and discussions, the FDA has voted unanimously to endorse betibeglogene autotemcel (beti-cel) for the treatment of patients with beta-thalassemia who require regular red blood cell (RBC) transfusions.
- Bluebird Bio presented a strong case for beti-cel in the treatment of beta-thal with emphasis on high transfusion-independent rate and 100% overall survival.
- The FDA agreed that AE profiles were expected within the scope of the disease.
- Concerns of longer engraftment time with beti-cel compared to allo-HSCT is not well understood.
- The FDA did not believe SAEs and malignancies observed in Bluebird’s eli-cel and lovo-cel should impact the safety profiles for beti-cel, but recommends long-term monitoring.
- Bluebird Bio continues to proactively recognize lentiviral vector insertions and acknowledge the need for follow-up.
- The company will place all enrolled patients from beti-cel clinical trials on a long-term study with additional 13 years of follow-up.
- Bluebird also plans to conduct a post-marketing registry, REG-501, to continue monitoring.
- The FDA voted to endorse beti-cel for beta-thal treatment but also recommends specific testing including tracking transduction percentage, insertion integration sites, and using NGS to monitor driver mutations with established baseline.
The endorsement of beti-cel is within expectations. Bluebird Bio was able to convince the FDA AdCom Panel of beti-cel’s efficacy with strong supporting data. Safety concerns for beti-cel were not as prominent as eli-cel. Main issues of oncogenesis with insertion mutations were addressed during eli-cel’s AdCom yesterday. The PUDFA date for beti-cel is scheduled for August 19th, 2022 when the FDA will make its final decision.