18 January 2022 - - The US Food and Drug Administration has extended the review period for the biologics licensing applications for US-based bluebird bio, Inc's (NASDAQ: BLUE) lentiviral vector gene therapies betibeglogene autotemcel (beti-cel) for β-thalassemia and elivaldogene autotemcel (eli-cel) for cerebral adrenoleukodystrophy, the company said.

The revised PDUFA goal dates for beti-cel and eli-cel are August 19, 2022 and September 16, 2022, respectively.

The FDA extended the PDUFA goal dates for beti-cel and eli-cel to allow time to review additional clinical information previously submitted by the company in response to FDA information requests as part of its ongoing reviews.

The information was deemed a major amendment. The extension of the FDA review timeline does not relate to new safety events for either beti-cel or eli-cel.

bluebird's BLA submission for beti-cel for adult, adolescent and pediatric patients with β-thalassemia across all genotypes who require regular red blood cell transfusions was accepted by the FDA for priority review in November 2021.

The FDA accepted the BLA for eli-cel for patients with cerebral adrenoleukodystrophy under the age of 18 for priority review in December 2021.

If approved, beti-cel and eli-cel would be the first lentiviral vector gene therapies for patients with severe genetic diseases in the United States.

The extended PDUFA goal dates are not expected to impact the priority review status of either BLA or the potential for bluebird bio to be granted priority review vouchers upon approval of beti-cel and eli-cel in 2022.

The FDA previously granted both beti-cel and eli-cel Orphan Drug status, Breakthrough Therapy designation and Rare Pediatric Disease designation.

Bluebird also provided an update on the FDA's partial clinical hold for the lovotibeglogene autotemcel (lovo-cel) gene therapy clinical program for patients under the age of 18 with sickle cell disease.

Consistent with the FDA's clinical hold process, the company has received written questions from the FDA and is continuing to evaluate what impact, if any, the partial clinical hold may have on its projected 1Q23 timing for submitting the BLA.

Bluebird said it plans to provide an update with its annual results in February.

betibeglogene autotemcel (beti-cel) (pronounced BEH tee cell) is a one-time gene therapy custom-designed to treat the underlying cause of β-thalassemia in patients who require regular red blood cell transfusions.

Beti-cel adds functional copies of a modified form of the β-globin gene (βA-T87Q-globin gene) into a patient's own hematopoietic (blood) stem cells in order to correct the deficiency of adult hemoglobin that is the hallmark of β-thalassemia.

Once a patient has the modified β-globin gene, they have the potential to produce beti-cel-derived adult hemoglobin (HbAT87Q) at levels that may eliminate the need for transfusions.

In Phase 3 beti-cel studies 89% (31/35) of evaluable patients across ages and genotypes, including pediatric patients as young as four years of age and those with the most severe β0/β0 genotypes, 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.

beti-cel is manufactured using the BB305 lentiviral vector, a third-generation, self-inactivating LVV that has been studied for more than a decade across two therapeutic areas.

Adverse reactions considered related to beti-cel consisted primarily of non-serious infusion-related reactions that occurred on the day of the infusion and cytopenias.

One serious adverse event of thrombocytopenia considered possibly related to beti-cel was reported and has resolved.

The majority of AEs and SAEs in the beti-cel clinical development program were considered to be unrelated to beti-cel by the Investigator and were consistent with known side effects of HSC collection and the busulfan conditioning regimen.

The Phase 3 Northstar-2 (HGB-207) and Northstar-3 (HGB-212) studies evaluating beti-cel are ongoing; enrollment is complete, and all patients have been treated.

bluebird bio is also conducting a long-term follow-up study, LTF-303, to monitor safety and efficacy for people who have participated in bluebird bio-sponsored beti-cel clinical studies through 15 years post treatment.

A biologics license application for beti-cel is under priority review by the FDA. The agency has set a Prescription Drug User Fee Act (PDUFA) goal date of August 19, 2022.