Posts by: Inês Martins PhD

Bluebird Bio remains on track to submit an application to the European Medicines Agency (EMA), requesting the approval of Lenti-D for boys with cerebral adrenoleukodystrophy (CALD) by year's end. Due to the COVID-19 pandemic, however, it expects to delay filing a similar request with the U.S. Food and Drug Administration (FDA) until mid-2021. “The COVID-19 pandemic has created new challenges for bluebird, the broader biotech community, and society as a whole. During this unprecedented time, we remain focused on caring for the patients who rely on us,” Nick Leschly, the company's CEO, said in a press release. Bluebird said it remains committed to the development of its investigational agents, but is following guidance from the government, regulatory authorities, and site institutions to reduce the risk of COVID-19 infections to all involved. It expects delays of at least three months for patient enrollment and data collection in ongoing trials. CALD is caused by mutations in the ABCD1 gene, which provides the instructions to make the ALD protein. This protein is needed to clear toxic molecules (namely, very long-chain fatty acids, or VLCFAs) in the brain, and the mutations disrupt its activity. As a result, toxic molecules accumulate and damage the protective coat of nerve cells (myelin). Current treatment includes stem cell transplants from donors. While such treatment may work to slow or stop progression, it can have unintended consequences, with some patients experiencing infections and graft-versus-host disease — a potentially life-threatening reaction in which the donor's immune cells attack and damage the patient's own cells and tissues. Bluebird's Lenti-D is an investigational cell-based therapy that uses the patients' own stem cells. These cells are taken from the bone marrow, modified in the lab to carry a working and healthy copy of the ABCD1 gene, and infused back into the patient. Once inside the body, Lenti-D cells can differentiate into different cell types, including brain cells, increasing the amount of functional ALD protein, and supporting the clearing of VLCFAs. Lenti-D's safety and efficacy is being investigated in ongoing studies in boys with CALD: the Starbeam Phase 2/3 trial (NCT01896102), its long-term extension study that follows treated patients for up to 15 years (NCT02698579), and the ALD-104 Phase 3 trial (NCT03852498). Results from Starbeam show that Lenti-D treatment stopped neurological decline and prevented further detrimental changes in the brain’s white matter in most patients. Most active brain lesions resolved after treatment. Patients followed in Starbeam's extension study for over two years were also free of severe complications, like an inability to communicate, wheelchair dependence, and a need for a feeding tube. No cases of graft-versus-host disease were reported. The ALD-104 study is now recruiting boys, up to 17 years old, to study the safety and effectiveness of Lenti-D, given after a preconditioning chemotherapy regimen with busulfan and fludarabine. This chemotherapy is often given to patients before a stem cell transplant, improving the likelihood that transplanted cells will survive and proliferate after being infused. Enrollment may be delayed, but those interested in taking part or learning more can contact study coordinators at sites in the U.S., France, Italy, and the U.K. These three studies, along with ongoing studies of two other investigational treatments — Ide-cel for multiple myeloma, and LentiGlobin for β-thalassemia and sickle cell disease — "remain active, but the effects of the COVID-19 pandemic is resulting in disruptions to study conduct across these programs," Bluebird said in the release. Lenti-D has been granted PRIME (Priority Medicine) and orphan drug medicinal product status by EMA for the treatment of CALD. It has also designated an orphan drug, rare pediatric disease, and breakthrough therapy by the FDA. "We are prioritizing the safety and well-being of our employees, making a positive impact as a member of our local community, and continuing to execute on our business strategy," Leschly said. "While we all face tremendous challenges and uncertainty at this time, I am confident in bluebird’s ability to face these headwinds with ingenuity, empathy, and a relentless commitment to the people we serve.”

Posts by: Inês Martins PhD

Inês Martins PhD

First Patient Dosed in NEXUS Phase 2 Trial of Leriglitazone in CALD

SwanBio Raises $52M to Support Studies of Gene Therapy for Adult-onset ALD

Bluebird to Request Lenti-D Approval for CALD in Europe, US Filing Delayed