FDA Grants Breakthrough Therapy Designation to Bluebird Bio’s Gene Therapy for CALD

Rare Daily Staff

The U.S. Food and Drug Administration granted Breakthrough Therapy designation to Bluebird Bio’s ALD-102, its experimental gene therapy for the treatment of patients with cerebral adrenoleukodystrophy, or CALD, a rare and life-threatening neurological condition.

CALD, also known as Lorenzo’s Oil disease, involves a breakdown of the protective sheath of the nerve cells in the brain that are responsible for thinking and muscle control. Currently, the only therapeutic option for patients with CALD is allogeneic hematopoietic stem cell transplant, but such treatment must be performed early in the progression of the disease and runs the risk of potentially fatal graft vs. host disease.

Bluebird’s ALD-102 is an experimental gene therapy that is made from a patient’s own immature bone marrow cells that are modified to include a functional copy of the ABCD1 gene to express functional ALD protein, which is lacking in patients with CALD. When the modified cells are infused back into the patient, they develop into different cell types, including brain cells. The expectation is that the expression of ALD protein in the brain can lead to a reduction in very long chain fatty acids, which are believed to contribute to potentially fatal neurodegeneration.

Breakthrough Therapy designation is designed to expedite the development and review of a drug intended, alone or in combination with one or more other drugs, to treat a serious or life-threatening disease when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.

“The founding of Bluebird was inspired by the potential to develop a one-time gene therapy for boys suffering from this potentially fatal form of adrenoleukodystrophy,” said David Davidson, chief medical officer, Bluebird Bio. “With [ALD-102], we hope the modified, autologous hematopoietic stem cells will keep these boys alive and free from major functional disabilities while avoiding many of the safety risks of the current standard of care, allogeneic hematopoietic stem cell transplant.”

The Breakthrough Therapy designation is supported by preliminary data from the ongoing phase 2/3 study ALD-102 in boys with CALD, 17 years of age or less who do not have a matched sibling donor. Findings from 17 patients were published in the New England Journal of Medicine in October 2017 and showed that 15 of the 17 patients (88 percent) infused with ALD-102 remained alive and free of major functional disabilities at 2 years post-treatment, the primary efficacy endpoint of the trial.

The FDA previously granted ALD-102 Orphan Drug designation, as well as Rare Pediatric Disease designation for the treatment of CALD. The European Medicines Agency granted ALD-102 Orphan Drug designation.

May 24, 2018
Photo: David Davidson, chief medical officer, Bluebird Bio