FDA Accepts IND for Gene-Edited Cell Therapy BIVV003 for Treatment of Sickle Cell Disease

Bioverativ and Sangamo announced that the US Food and Drug Administration (FDA) accepted the investigational new drug (IND) application for BIVV003, a gene-edited cell therapy candidate for treatment of sickle cell disease.

The IND allows Bioverativ to initiate a phase 1/2 clinical trial that will assess the safety, tolerability and efficacy of BIVV003 in adults with sickle cell disease. Bioverativ expects to open multiple clinical sites across the US this year.

“Sickle cell disease is a lifelong blood disorder with serious, painful and debilitating complications and patients deserve new, more effective treatment options,” Ed Conner, MD, chief medical officer, Sangamo, said in a statement. “Gene-edited 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 zine finger nuclease technology differentiate BIVV003 from other genomic therapies in development.”

BIV0003, an autologous cell therapy that involves gene editing of a patient’s own hematopoietic stem cells, uses a non-viral zine finger nuclease (ZFN) gene-editing technology.

As part of the clinical trial protocol, a patient’s hematopoietic stem cells are isolated from the blood and then undergo ex vivo gene editing using ZFNs to modify the erythroid enhancer of the BCL11A gene.

Following a bone marrow condition regimen, patients are then infused with their own hematopoietic stem cells, with the goal of producing red blood cells that have increased production of fetal hemoglobin. Utilizing a patient’s own cells reduces the risk of graft failure and eliminates the risk of graft-versus-host disease and the need for immunosuppression.

The sickle mutation causes red blood cells to have an abnormal sickle or crescent shape, which makes them inefficient in oxygen-carrying capacity, leading to chronic anemia, vaso-occlusive crises with severe pain, multi-organ damage, complications like stroke and a shortened life expectancy.

“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,” Ken Huttner, MD, PhD, vice president, clinical development, Bioverativ, said in a statement.

Sangamo is currently enrolling patients with transfusion-dependent beta thalassemia in a phase 1/2 trial to evaluate the safety, tolerability and efficacy of ST-400—a treatment that utilizes the same gene-editing approach as BIVV003.