If approved, eli-cel will be the first and only gene therapy for the treatment of early active CALD, a rare neurodegenerative disease that primarily affects young children and leads to irreversible loss of neurologic function and death
PDUFA goal date is set for
On the question “Do the benefits of eli-cel outweigh the risks, for the treatment of any sub-population of children with early active cerebral adrenoleukodystrophy (CALD)?” the CTGTAC voted 15 (yes) to 0 (no).
“For decades, the CALD community has fought for the opportunity to stave off the rapid, irreversible decline associated with this devastating disease,” said
CALD is a rare, progressive, neurodegenerative disease that primarily affects young boys and causes behavioral, cognitive, and neurological deficits. Nearly half of patients who do not receive treatment die within five years of symptom onset. Allogeneic hematopoietic stem cell transplant (allo-HSCT) is currently the only effective treatment option but is associated with serious potential complications and mortality that increase in patients without a matched sibling donor. If approved, eli-cel will be the first approved gene therapy to address the underlying genetic cause of disease for patients living with CALD in the
The committee’s recommendation is based on the Biologics License Application (BLA) currently under priority review by the FDA with a PDUFA goal date set for
The eli-cel clinical program was placed on a clinical hold following a Suspected Unexpected Serious Adverse Reaction (SUSAR) of myelodysplastic syndrome (MDS) in
The CTGTAC also discussed the overall safety of lentiviral vector (LVV) gene therapies, concluding in a 13 to 1 vote that the safety data from lovo-cel for sickle cell disease is not relevant to the review of eli-cel. In addition to granting eli-cel BLA priority review, the FDA previously granted eli-cel Orphan Drug status, Rare Pediatric Disease designation, and Breakthrough Therapy designation. bluebird bio is eligible to receive a priority review voucher upon potential approval of eli-cel.
Adrenoleukodystrophy (ALD) is a rare, X-linked metabolic disorder that primarily affects males; worldwide, an estimated one in 21,000 male newborns are diagnosed with ALD. The disorder is caused by mutations in the ABCD1 gene that affect the production of adrenoleukodystrophy protein (ALDP) and subsequently leads to toxic accumulation of very long-chain fatty acids (VLCFAs), primarily in the adrenal gland and white matter of the brain and spinal cord. Approximately 40% of boys with ALD will develop CALD, the most severe form of ALD. CALD is a progressive and irreversible neurodegenerative disease that involves the breakdown of myelin, the protective sheath that nerve cells need to function effectively, especially for thinking and muscle control. The onset of symptoms of CALD typically occurs in childhood (median age 7). Early diagnosis and treatment of CALD is essential, as nearly half of patients who do not receive treatment die within five years of symptom onset.
About elivaldogene autotemcel (eli-cel) gene therapy
eli-cel (pronounced ELL ee cell) uses ex vivo transduction with the Lenti-D lentiviral vector (LVV) to add functional copies of the ABCD1 gene into a patient’s own hematopoietic stem cells (HSCs). The addition of the functional ABCD1 gene allows patients to produce the ALD protein (ALDP), which is thought to facilitate the breakdown of very long-chain fatty acids (VLCFAs). The expression of ALDP and effect of eli-cel is expected to be life-long. The goal of treatment with eli-cel is to stop the progression of CALD and, consequently, preserve as much neurological function as possible, including the preservation of motor function and communication ability. Importantly, with eli-cel, there is no need for donor HSCs from another person.
bluebird bio’s clinical development program for eli-cel includes the completed pivotal Phase 2/3 Starbeam study (ALD-102) and the ongoing Phase 3 ALD-104 study, which has completed enrollment and treatment of all patients. Additionally, bluebird bio is conducting a long-term safety and efficacy follow-up study (LTF-304) for patients who have received eli-cel for CALD and completed two years of follow-up in ALD-102 or ALD-104. Enrollment into studies of eli-cel is currently on hold with the FDA and follow-up of all patients continues, per protocol.
In ALD-102, 90.6% (29/32) of patients met the primary endpoint of Major Functional Disabilities (MFD)-free survival at 24 months. As previously reported, two patients withdrew from study ALD-102 at investigator discretion, and one additional subject experienced rapid disease progression early after treatment, resulting in MFDs and subsequent death. All patients who completed ALD-102 enrolled in a long-term follow-up study (LTF-304). The median duration of follow-up is approximately four years (49 months; 13.4, 88.1).
Adverse reactions attributed to eli-cel observed in clinical trials include myelodysplastic syndrome, viral cystitis, pancytopenia, and nausea and vomiting. There have been no reports of graft-versus-host-disease, graft failure or rejection, transplant-related mortality, or replication competent lentivirus in the 67 patients who received eli-cel in clinical studies (ALD-102, ALD-104, LTF-304).
About bluebird bio, Inc.
bluebird bio is pursuing curative gene therapies to give patients and their families more bluebird days.
With a dedicated focus on severe genetic diseases, bluebird has industry-leading clinical and research programs for sickle cell disease, beta-thalassemia and cerebral adrenoleukodystrophy and is advancing research to apply new technologies to these and other diseases. We custom design each of our therapies to address the underlying cause of disease and have developed in-depth and effective analytical methods to understand the safety of our lentiviral vector technologies and drive the field of gene therapy forward.
Founded in 2010, bluebird has the largest and deepest ex-vivo gene therapy data set in the world—setting the standard for industry. Today, bluebird continues to forge new paths, combining our real-world experience with a deep commitment to patient communities and a people-centric culture that attracts and grows a diverse flock of dedicated birds.
Lenti-D and bluebird bio are trademarks of bluebird bio, Inc.
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