SKYSONA is the first and only gene therapy recommended for approval for patients with CALD, a progressive, neurodegenerative disease
As of the data cutoff date, 90% of patients (27/30) treated with SKYSONA in the pivotal ALD-102 clinical study met the primary endpoint of major functional disability (MFD)-free survival at two years of follow-up
Data from the long-term follow-up study (LTF-304) suggest that SKYSONA continues to show a durable effect on MFD-free survival, with the longest follow-up of nearly seven years (82.7 months)
Among 51 patients treated with SKYSONA across clinical studies to date, there have been no reports of graft-versus-host disease (GVHD), graft failure or rejection, or transplant-related mortality (TRM)
The CHMP’s positive opinion will now be reviewed by the EC, which has the authority to grant marketing authorization for SKYSONA in the
“The goal of treatment with SKYSONA is to stabilize disease progression in children with CALD for whom a matched sibling donor is not available, in order to prevent further neurological decline and improve survival for these young patients,” said
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 cause 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 of the nerve cells in the brain responsible for thinking and muscle control. The onset of symptoms of CALD typically occurs in childhood (median age 7).
“The rapid and progressive decline of cognitive and physical functions for a child living with CALD is agonizing for parents, families and healthcare providers to witness. With CALD, each day truly counts, as nearly half of the patients who do not receive treatment will die within five years of symptom onset,”1 said
“Families affected by CALD face a critical diagnosis, as symptoms that generally develop in childhood result in a progressive loss of autonomy and rapid neurological decline. There is an urgent need for treatment options,” said
SKYSONA is a one-time investigational gene therapy that 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 (blood) stem cells (HSCs). The addition of the functional ABCD1 gene allows patients to produce the ALD protein, which is thought to facilitate the breakdown of VLCFAs. The goal of treatment with SKYSONA is to stabilize the progression of CALD and, consequently, preserve as much neurological function as possible, including the preservation of motor function and communication ability. Importantly, with SKYSONA, there is no need for donor HSCs from another person.
Data Supporting Clinical Profile of SKYSONA
The positive CHMP opinion is supported by efficacy and safety data from the Phase 2/3 Starbeam study (ALD-102). All patients who completed ALD-102, plus those who will complete a second Phase 3 study (ALD-104), will be asked to participate in a long-term follow-up study (LTF-304).
The primary efficacy endpoint of the pivotal ALD-102 study was the proportion of patients who did not have any of the six MFDs, were alive, did not receive a second allo-HSCT or rescue cell administration and had not withdrawn or been lost to follow-up at Month 24. To date, 32 patients have been treated with SKYSONA in ALD-102, and 30/32 patients were evaluable for follow-up at Month 24. As of the last data cutoff date, 90% (27/30) of the patients met the Month 24 MFD-free survival endpoint. In addition, as previously reported, two patients withdrew from the study at investigator discretion, and one experienced rapid disease progression early on in the study, resulting in MFDs and subsequent death.
In ALD-102, 26/28 evaluable patients maintained a neurologic function score (NFS) less than or equal to 1 through Month 24, and 24 of those patients had no change in their NFS, which showed maintenance of neurological function in the majority of patients. All patients who completed ALD-102 enrolled for long-term follow-up in the LTF-304 study. The median duration of follow-up was 38.59 months (min.: 13.4; max.: 82.7).
The treatment regimen, comprising mobilization/apheresis, conditioning and SKYSONA infusion, had a safety/tolerability profile primarily reflective of the known effects of mobilization/apheresis and conditioning.
Adverse reactions attributed to SKYSONA observed in clinical trials include cystitis viral, pancytopenia and vomiting.
There have been no reports of GVHD, graft failure or rejection, TRM or replication competent lentivirus in the 51 patients treated with SKYSONA in clinical studies (ALD-102/LTF-304 and ALD-104). Additionally, there have been no reports of lentiviral vector-mediated insertional mutagenesis resulting in oncogenesis, including myelodysplasia, leukemia or lymphoma, associated with SKYSONA. Nevertheless, there is a theoretical risk of malignancy after treatment with SKYSONA. Clonal expansion resulting in clonal predominance without clinical evidence of malignancy has been detected in some patients treated with SKYSONA.
SKYSONA continues to be evaluated in the Phase 3 ALD-104 study and the long-term follow-up study LTF-304. If approved by the EC, patients treated with SKYSONA in
About SKYSONA (elivaldogene autotemcel, formerly Lenti-D™ gene therapy)
SKYSONA is not approved for any indication in any geography.
The Phase 3 ALD-104 study, designed to assess the efficacy and safety of SKYSONA after myeloablative conditioning using busulfan and fludarabine in patients with CALD, is approaching enrollment completion; enrollment in
Additionally, bluebird bio is conducting a long-term safety and efficacy follow-up study (LTF-304) for patients who have been treated with SKYSONA for CALD and completed two years of follow-up in bluebird bio-sponsored studies. If approved by the EC, patients treated with SKYSONA in
About CALD Early Diagnosis
Early diagnosis of CALD is essential, as treatment must be administered before the disease progresses too far, as the outcome of treatment varies with the clinical stage of the disease. Newborn screening is a critical enabler of early diagnosis for ALD and provides access to a window of opportunity for the timely commencement of available therapies. Once a patient has been diagnosed with ALD, regular MRI scans are critical to detect white matter changes indicative of progression to CALD as currently, there is no way to predict who with ALD will develop CALD. In the absence of newborn screening for ALD, early detection of ALD symptoms is crucial to allow for timely treatment.
Unfortunately, in most EU countries, there is no newborn screening for ALD, and therefore it is difficult to detect patients at risk of developing CALD. To date,
About bluebird bio, Inc.
bluebird bio is pioneering gene therapy with purpose. From our
bluebird bio is a human company powered by human stories. We’re putting our care and expertise to work across a spectrum of disorders: cerebral adrenoleukodystrophy, sickle cell disease, β-thalassemia and multiple myeloma, using gene and cell therapy technologies including gene addition, and (megaTAL-enabled) gene editing.
bluebird bio has additional nests in
SKYSONA, eli-cel, Lenti-D and bluebird bio are trademarks of bluebird bio, Inc.
This release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding the company’s expectations and plans for regulatory submissions and approvals for eli-cel in the
1 Reported Kaplan-Meier estimated five-year survival rates among untreated patients are 55% (from the time of CALD diagnosis) and 59% (from the time of onset of first clinical symptoms).
Source: bluebird bio, Inc.