FDA halts trial of gene therapy for rare neurological disease due to cancer risk
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The FDA placed a clinical hold on a phase 3 study designed to evaluate elivaldogene autotemcel, an investigational gene therapy, for the treatment of younger patients with cerebral adrenoleukodystrophy.
Cerebral adrenoleukodystrophy is an inherited genetic condition that causes damage to the myelin sheath that insulates nerve cells within the brain. The damage prevents the body from breaking down certain fatty acids and causes a buildup in the nervous system that typically causes death within 10 years of symptom onset.
The FDA placed the ALD-104 study on hold after one patient who received elivaldogene autotemcel (Lenti-D, bluebird bio) developed myelodysplastic syndrome, a condition that affects the blood-forming cells within the bone marrow and often progresses to acute myeloid leukemia.
“Evidence currently available suggests that specific design features of Lenti-D [lentiviral vector] likely contributed to this event,” a bluebird bio-issued press release stated. “The company has shared this information with the independent data monitoring committee of the study.”
Lentivirus vectors are used in gene therapy to transport genetically altered material into a patient’s stem cells.
Eli-cel is an autologous gene therapy derived from a patient’s CD34-positive hematopoietic stem cells. The cells are transduced ex-vivo using the Lenti-D lentiviral vector encoding human adrenoleukodystrophy protein and are transplanted back into the patient after a myeloablative preconditioning regimen.
“Our hearts go out to this patient and his family, who are dealing with a challenging diagnosis,” Nick Leschly, CEO of bluebird bio, said in the release. “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.”
Ongoing clinical trials of other gene therapy products produced by bluebird bio — including studies of patients with sickle cell disease and beta-thalassemia — are not affected by the clinical hold, according to the release.
As Healio previously reported, the FDA earlier this year placed holds on four other studies designed to evaluate two other bluebird bio gene therapies for hematologic conditions. The FDA lifted the clinical holds in June.
Additionally, bluebird bio representatives still anticipate completing a rolling submission to the FDA of its biologics license application for eli-cel by the end of this year, pending resolution of the trial’s clinical hold.
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