The hold is related to a report of a SUSAR of myelodysplastic syndrome in a patient treated with eli-cel, also known as Lenti-D, in a Phase III clinical trial.
Shares of bluebird bio were down more than 24% after the company announced that the U.S. Food and Drug Administration placed a clinical hold on studies of its elivaldogene autotemcel (eli-cel) gene therapy for cerebral adrenoleukodystrophy (CALD).
In its second quarter financial and business highlights, the hold is related to a report of a Suspected Unexpected Serious Adverse Reaction (SUSAR) of myelodysplastic syndrome in a patient treated with eli-cel, also known as Lenti-D in a Phase III clinical trial. Bluebird said the patient was treated with the gene therapy more than one year ago.
“Evidence currently available suggests that specific design features of Lenti-D LVV likely contributed to this event,” bluebird said in its announcement.
Cambridge, Mass.-based bluebird shared the information regarding the patient with the Independent Data Monitoring Committee, which resulted in the clinical hold. Once the concerns of the hold have been addressed, bluebird anticipates completing the submission of the rolling BLA for eli-cel in 2021.
The company added that it does not anticipate any impact on its other gene therapy programs for sickle cell disease (SCD), β-thalassemia or oncology. Bluebird’s LentiGlobin for sickle cell and β-thalassemia was placed on clinical hold in February due to safety concerns.
In June, the FDA lifted those holds following a review of data. Last year, the company announced it will not likely submit a New Drug Application for its sickle cell LentiGlobin therapy until 2022 following a new agreement with the FDA.
Chief bluebird Nick Leschly expressed concern for the patient diagnosed with myelodysplastic syndrome, a type of cancer where the production of blood cells is disrupted.
“Given what we know, we remain confident that eli-cel can offer hope for patients and families impacted by this devastating disease who have very few treatment options. We are committed to working with regulators and physicians in order to resolve this hold as soon as possible and bring this important therapy to patients in need,” Leschly said in a statement.
Elivaldogene autotemcel has been approved in Europe under the brand name Skysona. It was also approved in June for juvenile patients with early Cerebral Adrenoleukodystrophy (CALD), a severe neurological disorder caused by mutations in the ABCD1 gene.
When there are mutations in this gene, it impacts the way cells metabolize very long-chain fatty acids (VLCFAs). This causes a buildup in the central nervous system and blood, which causes the breakdown of the myelin, the protective sheath around nerve cells in the brain.
CALD typically develops in a juvenile around the age of seven.
According to bluebird, eli-cel uses ex vivo transduction with the Lenti-D lentiviral vector (LVV) to add functional copies of the ABCD1 gene into a patient’s own hematopoietic stem cells (hsc). The addition of the functional ABCD1 gene allows patients to produce the ALD protein (ALDP), which is thought to aid the breakdown of VLCFAs.
The clinical hold comes as bluebird continues to work on its impending split into two companies, one that will focus on genetic diseases, such as CALD, and an oncology business.
