Gene Therapy
Regulatory & Standards
Stem Cells
Viral/Non-Viral Vectors

Two bluebird bio Gene Therapies Achieve Unanimous FDA Support

Anna Osborne
16 June 2022
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Bluebird bio celebrates a big win as two of their gene therapy products, bet-cel and eli-cel, win over the FDA, gaining endorsement to treat two separate indications: Beta-thalassemia and cerebral adrenoleukodystrophy (CALD), respectively.

The FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee (CTGTAC) discussed the efficacy and safety of these gene therapies, and unanimously voted yes when asked: “Do the benefits of beti-cel outweigh the risks for the treatment of subjects with transfusion-dependent beta-thalassemia?” and “do the benefits of eli-cel outweigh the risks, for the treatment of any sub-population of children with early active cerebral adrenoleukodystrophy (CALD)?”

Nearly half of the patients who suffer from the rare, progressive, neurodegenerative disease, CALD, do not receive any treatment and die within five years of symptom onset. Assuring approval, eli-cel will be the first marketed gene therapy for CALD, offering hope to the 70% of patients diagnosed with CALD who do not have a match for the current standard of treatment, an allogeneic hematopoietic stem cell transplant.

The committee’s recommendation of eli-cel is based on the FDA’s priority review of its Biologics License Application (BLA), with a PDUFA goal set for September 2022.

“Today we are one step closer to delivering a potentially lifesaving therapy for CALD. We are grateful to the families, clinicians, and committee members who participated in today’s advisory committee discussion and remain committed to working with the FDA as it completes its review of the eli-cel Biologics License Application,” commented Andrew Obenshain, CEO of bluebird bio.

Eli-cel’s BLA is based on data from Phase II and III clinical trials investigating its effect on patients with CALD. Study results showed that patients treated with eli-cel were more likely to achieve overall and event-free survival than both patients without any allo-HSCT donor matches, and, patients without an allo-HSCT matched sibling donor.

In the Phase II/III ALD-102 clinical study 90.6% of patients treated with eli-cel met the primary end-point of Major Functional Disabilities-free survival at a 24-month follow-up.

Using ex vivo transduction with a lentiviral vector, eli-cel adds functional copies of the ABCD1 gene into the patient’s hematopoietic stem cells stimulating ALD protein production and facilitating the breakdown of very-long-chain fatty acids, preventing their toxic accumulation – the cause of CALD.

Despite the positive FDA opinion, the eli-cel clinical program has currently been put on hold due to three Suspected Unexpected Serious Adverse Reactions (SUSAR) of myelodysplastic syndrome, in the trial populations. All patients involved in the trials are receiving close monitoring.

The committee’s recommendation of the investigational lentiviral vector gene therapy beti-cel for the treatment of the rare genetic blood disease, beta-thalassemia, is based on the FDA’s priority review of its Biologics License Application (BLA) – results of which are expected by August 2022.

“Today’s advisory committee recommendation is recognition of the substantial body of clinical data that support beti-cel as a potentially curative treatment option for these patients. We are grateful to the members of the beta-thalassemia community who contributed to today’s discussion and remain committed to working with the FDA as it completes its review of the beti-cel Biologics License Application,” commented Andrew Obenshain, CEO of bluebird bio.

This one-time gene therapy saves the requirement for regular red blood cell transfusions – the current treatment of beta-thalassemia – though adding functional copies of a modified form of the beta-globin gene into hematopoietic stem cells correcting the patient’s deficiency of hemoglobin.

Beti-cel was granted priority review on their BLA based upon data from bluebird’s Phase III, Phase I/II, and long-term follow-up studies. As well as data from bluebird’s clinical development program that represents 240 patient-years of beti-cel experience – the longest available follow-up data of beta-thalassemia patients treated with a one-time gene therapy.

Evaluation of safety in these clinical trials showed infrequent and, generally, non-serious infusion-related adverse reactions to beti-cel.

Prior to its BLA priority review status, both beti-cel and eli-cel were granted Orphan Drug status and Breakthrough Therapy designation, with eli-cel also receiving Rare Pediatric Disease designation.

Sources: Bluebird bio Press Releases: 9/06/2022 and 10/06/2022

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