Our Product Pipeline
CCALD Product Development
Our Lenti-D product candidate has the potential to be a one-time treatment to stabilize the disease and prevent progression of childhood cerebral adrenoleukodystrophy (CCALD). Our approach involves the ex vivo insertion of a functional copy of the ABCD1 gene into a patient's own hematopoietic stem cells. We are involved with an ongoing Phase 1/2 clinical program in France. Early promising clinical proof-of-concept results for two patients in a French study sponsored by INSERM and licensed by bluebird bio were reported in the November 2009 issue of Science. The safety and therapeutic benefits have been maintained for more than five years, and two additional patients have subsequently been treated. We are developing a next generation product, called Lenti-D, for which we plan to initiate a larger Phase 2/3 clinical study called the ALD-102 Study in CCALD in the United States and Europe in 2013. We were granted orphan drug designation for Lenti-D by both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) in 2012.
Adrenoleukodystrophy (ALD) is a rare X-linked, inherited neurological disorder that, in its most severe form, causes breakdown of the myelin sheath in the brain (a protective and insulating membrane that surrounds nerve cells) and progressive dysfunction of the adrenal glands. This damage can result in decreased motor coordination and function, visual and hearing disturbances, the loss of cognitive function, dementia, seizures, adrenal dysfunction and other complications, including death. Also known as Lorenzo's Oil disease, ALD is estimated to affect approximately one in every 20,000 boys worldwide. In the childhood cerebral form (CCALD), symptoms usually occur between the ages of 3 and 15 years. Boys afflicted with this form of ALD develop normally until the onset of symptoms. Symptoms often progress rapidly and, in a matter of months or years, can lead to a vegetative state and, ultimately, death.
Currently, the only effective treatment option is allogeneic hematopoietic stem cell transplant (HSCT), in which the patient is treated with HSCs containing the properly functioning copy of the gene contributed by a donor other than the patient. HSCT is typically performed early in the course of the disease using an unaffected matched sibling HSC donor, although non-sibling matched donor cells and cord blood cells are also used. However, allogeneic HSCT is associated with significant morbidity and mortality, particularly in patients who undergo non-sibling matched allogeneic HSCT. Unfortunately, sibling matched donors are only typically available for less than 30% of patients. Allogeneic HSCT carries a significant risk of morbidity and mortality related to serious infection, graft failure and graft-versus-host-disease.