The European Medicines Agency (EMA) accepted an application requesting approval of the gene therapy Lenti-D (elivaldogene autotemcel, or eli-cel) to treat cerebral adrenoleukodystrophy (CALD), its developer, Bluebird Bio, announced.
If approved, the submission — in the form of a marketing authorization application (MAA) — will be reviewed by the European Commission, which makes final decisions on whether a therapy can be marketed.
According to Bluebird Bio, the EMA may complete its review of Lenti-D in about five months (190 days) instead of the usual nearly seven months (210 days), as its Committee for Medicinal Products for Human Use granted the therapy an accelerated assessment.
“CALD is a devastating disease, often marked by rapid neurodegeneration, the development of major functional disabilities, and eventual death. The acceptance of the MAA for eli-cel [Lenti-D] is a critical milestone in our continued collaboration with the EMA to potentially deliver an autologous gene therapy for boys with CALD,” Gary Fortin, PhD, head of severe genetic diseases at Bluebird Bio, said in a press release.
CALD is the most severe form of adrenoleukodystrophy, caused by mutations in the ABCD1 gene that contains information to produce ALD protein. ALD is required to clear very long-chain fatty acids (VLCFAs) which, without this protein, accumulate and turn toxic to damage myelin, the protective layer of nerve cells called myelin.
Current treatment for the disease is based on stem cell transplants that can slow or stop disease progression. However, such transplants can carry considerable side effects, Bluebird reported in its release, including serious reactions to donor immune cells attacking and damaging the patient’s own cells and tissues (graft-versus-host disease) and infections.
Lenti-D is an investigational gene therapy using a patient’s own stem cells — namely, hematopoietic (blood) stem cells. These cells are collected from the bone marrow, modified to hold a functional and healthy copy of the ABCD1 gene, and returned to the patient.
The healthy gene that is delivered is expected to allow the production of a working ALD protein, to clear VLCFAs.
Bluebird’s application is supported by results from three studies assessing Lenti-D’s safety and efficacy in boys with CALD: the Starbeam Phase 2/3 trial (ALD-102, NCT01896102), its long-term follow-up study (NCT02698579), and the ongoing and enrolling Phase 3 ALD-104 study (NCT03852498). More information on this open-label trial, recruiting boys up to age 17 in select U.S. and European sites, is available here.
Data from the Phase 2/3 trial showed that Lenti-D treatment resolved most active brain lesions and stopped neurological deterioration. Patients were also free of infections and other severe problems, including wheelchair dependency or the need for a feeding tube. No cases of graft-versus-host disease were reported.
Starbeam results and early data from the other trials were presented in August at the 46th Annual Meeting of the European Society for Blood and Marrow Transplantation.
“Data from clinical studies conducted in patients with early CALD suggest eli-cel [Lenti-D] stabilizes the progression of the disease,” Fortin said.
“If approved, eli-cel would represent the first therapy for CALD that uses a patient’s own hematopoietic stem cells, potentially mitigating the risk of life-threatening immune complications associated with transplant using cells from a donor,” he added.
Lenti-D received a Priorities Medicines program (PRIME) designation, and an orphan drug medicinal product designation for the treatment of CALD from the EMA. The U.S. Food and Drug Administration (FDA) has also designated this therapy an orphan drug, rare pediatric disease, and breakthrough therapy.
A similar approval request, called a biologics license application, is expected to be filed with the FDA in mid-2021, according to Bluebird Bio.
