DURHAM – bluebird bio, a gene therapy company with operations in Durham, has received Breakthrough Therapy designation from the U.S. Food and Drug Administration for Lenti-D, its potential treatment for a rare and life-threatening neurological disorder in boys.

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The FDA designation is designed to quicken the development and review of drugs that may work better than existing therapies, based on preliminary clinical evidence.

Lenti-D is intended to treat boys suffering from cerebral adrenoleukodystrophy (CALD), a hereditary disease that involves a breakdown of the protective sheath of the nerve cells in the brain that are responsible for thinking and muscle control.

Lenti-D therapy replaces a mutated gene with a functional gene in a patient’s own immature bone marrow cells, called autologous hematopoietic stem cells. When the modified cells are given back to the patient, they develop into different cell types, including brain cells, and begin producing a protein that is lacking. The restored protein is believed to prevent the buildup of fatty acids in the brain that are thought to contribute to neurodegeneration.

Currently, the only proven effective treatment option for CALD is a bone marrow transplant, also called a stem cell transplant or allogeneic hematopoietic stem cell transplant, which carries life-threatening safety risks.

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,” Davidson said. “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, M.D., chief medical officer of bluebird bio. “With Lenti-D, 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 FDA designation was supported by preliminary data from an ongoing Phase 2/3 study, called Starbeam, evaluating Lenti-D in boys with CALD who are 17 years old or less and who do not have a matched sibling bone marrow donor. Results published in the New England Journal of Medicine in October 2017 showed that 15 of the 17 patients infused with Lenti-D remained alive and free of major functional disabilities at two years after treatment, the trial’s primary efficacy endpoint.

Patients who complete the Starbeam trial subsequently enroll in a long-term follow-up study to monitor their progress.

An estimated one in every 21,000 males born worldwide inherit adrenoleukodystrophy (ALD), also known as Lorenzo’s Oil disease. About 40 percent of them will progress to the cerebral form of the disease, CALD.

Durham production plant ramping up

bluebird is using a contract manufacturing organization to make Lenti-D but will eventually transition production to a 125,000-square-foot manufacturing plant it purchased last year in Durham.

“Over time, it is our intent to have the (Durham) facility support all of our programs,” said Stephanie Fagan, bluebird’s senior vice president of corporate communications. “Our long-term manufacturing strategy is a combination of internal capabilities and external partnerships, and we believe we are well-positioned to meet current and future supply needs.”

The Durham site’s initial build-out will allow for production of clinical and commercial supply of lentiviral vector, a critical component of the company’s gene and cell therapies.

bluebird, a publicly traded company based in Cambridge, Mass., also has operations in Seattle, and Zug, Switzerland. The company has over 500 employees and expects to have more than 700 by the end of this year, Fagan said.

“These headcounts are to support continued commercialization efforts in the United States and European Union, along with ramping up internal manufacturing capabilities at our North Carolina facility,” she said.
In addition to Lenti-D, bluebird is developing investigational therapies for patients with transfusion-dependent β-thalassemia, severe sickle cell disease and multiple myeloma.

Other companies announcing gene therapy production facilities in North Carolina recently include Pfizer, which is investing $100 million and adding gene therapy capabilities to its campus in Sanford, and AveXis, which is investing $55 million in a new Durham manufacturing plant that will create 200 jobs.