CALD Gene Therapy Granted Breakthrough Therapy Designation

Supported by positive data from an ongoing Phase 2/3 study, bluebird bio’s Lenti-D has been granted Breakthrough Therapy designation by the US Food and Drug Administration (FDA) for the treatment of patients with cerebral adrenoleukodystrophy (CALD), or Lorenzo’s Oil disease.

The gene therapy is comprised of a patient’s own immature bone marrow cells and modifies them to include a functional copy of the ABCD1 gene. The alteration permits the expression of functional ALD, the deficient protein in the patient population.

Preliminary findings from the ongoing Starbeam Study (ALD-102) evaluating the investigational gene therapy in boys with CALD aged 17 years or younger who do not have a matched sibling donor were published in the New England Journal of Medicine (NEJM) in October 2017 and showed that the drug hit its primary efficacy endpoint. In the study, 88% (n=15) of patients infused with Lenti-D remained alive and free of major functional disabilities at 2 years post-treatment.

Additionally, the data showed that the safety profile of Lenti-D remains consistent with myeloablative chemotherapy. No instances of engraftment failure, graft versus host disease (GVHD) or treatment-related mortality were reported, nor was there any evidence of insertional oncogenesis.

In October, Rare Disease Report sat down with Mohammed Asmal, Vice President, Clinical Development at bluebird bio, to learn about the data published in NEJM, the motivation behind the development of this potential therapeutic option.

“The impetus for the start of the study came from the patients who don’t have matching donors; they don’t have good outcomes,” he said. “We needed to find an alternative, and the theory that gene therapy can correct something like this was certainly out there.”

“The mechanism by which this would work is very much like how stem cell therapy transplantation is able to correct the disease. The theory was certainly there, it just relied on someone, essentially, being willing to develop the vector and then try it on patients who did not have any other feasible options for transplant, and who had poor predicted outcomes for transplant survival.”

At present, the only available therapeutic option for patients with CALD is allogeneic hematopoietic stem cell transplant (HSCT). While clinical benefit has been reported if performed early during CALD progression, potential complications of allogeneic HSCT can be fatal.

Previously, bluebird’s Lenti-D investigational gene therapy had been granted Orphan Drug designation by both the FDA and European Medicines Agency (EMA) in addition to Rare Pediatric Disease designation by the FDA for the treatment of adrenoleukodystrophy (ALD).

“The FDA’s Breakthrough Therapy designation for Lenti-D brings us one step closer to realizing this mission to bring new hope to the patients and families affected by this devastating disease,” said David Davidson, MD, chief medical officer, bluebird bio in a press release. “We look forward to continuing to work closely with the FDA and EMA to expedite development of Lenti-D as a treatment for CALD.”

For more from the rare disease community, subscribe to Rare Disease Report’s e-newsletter.