Rare Disease Report

FDA Accepts IND Application for BIVV003, a Gene Therapy for Sickle Cell Disease

MAY 16, 2018
Krista Rossi
This morning, Bioverativ Inc, announced that the US Food and Drug Administration (FDA) has accepted the company’s Investigational New Drug (IND) application for BIVV003, a gene-edited cell therapy candidate for the treatment of people with sickle cell disease.
Together, through their development of BIVV003, Bioverativ and Sangamo are working to progress and commercialize gene-edited cell therapies for sickle cell disease and beta thalassemia.

“This acceptance marks the second IND for this gene-editing approach in less than a year and the first for a gene-edited therapy in sickle cell disease,” commented Ken Huttner, MD PhD, Vice President, Clinical Development at Bioverativ in a recent statement. “It represents our commitment to advancing cutting-edge science and offers hope to the many people who have been waiting for generations for an effective way to treat sickle cell disease. We look forward to advancing the program into clinical trials.”

BIVV003 is a non-viral approach that utilizes zinc finger nuclease (ZFN) gene-editing technology to gene edit a patient’s own hematopoietic stem cells (HSCs). The treatment suppresses sickle hemoglobin production while reactivating the production of fetal hemoglobin to levels that may protect patients against disease progression. This action is due to the treatment’s mechanism that modifies a short sequence of the BCL11A gene in a patient’s red blood cell precursors.

With the FDA’s IND acceptance, a phase 1/2 clinical trial that will assess the safety, tolerability, and efficacy of BIVV003 in adults with sickle cell disease is now possible. Consequently, Bioverativ plans to open several clinical sites throughout the United States this year.

The phase 1/2 clinical trial will require, as a protocol, that a patient’s HSCs be isolated from the blood before undergoing a non-viral, ex vivo gene editing, which will utilize ZFNs to adjust the erythroid enhancer of the BCL11A gene, a key player in the function of regulating fetal hemoglobin levels. Patients will also be infused with their own modified HSCs following a bone marrow conditioning regimen; this process will aim at producing red blood cells that contain an increased production of fetal hemoglobin.

Using a patient’s own cells lessens the risk of graft failure and eliminates the risk of graft-versus-host disease and the need for immunosuppression that is associated with transplant from a donor.

“Sickle cell disease is a lifelong blood disorder with serious, painful and debilitating complications, and patients deserve new, more effective treatment options,” added Ed Conner, MD, Chief Medical Officer at Sangamo. “Gene-edited cell therapy has the potential to provide patients living with sickle cell disease a lifelong treatment with a single administration. We believe the precision, efficiency, and specificity of zinc finger nuclease technology differentiate BIVV003 from other genomic therapies in development.”

At present, Sangamo is recruiting subjects for a phase 1/2 trial that will evaluate the safety, tolerability, and efficacy of ST-400, which utilizes the same gene-editing approach as BIVV003. Participants will have transfusion-dependent beta thalassemia.

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