The U.S. Food and Drug Administration recently accepted an investigational new drug (IND) application submitted by Bioverativ and Sangamo Therapeutics for BIVV003, a gene-edited cell therapy candidate for the treatment of sickle cell disease.
BIVV003 uses a nonviral approach that uses zinc finger nuclease (ZFN) gene-editing technology to modify a short sequence of the BCL11A gene in red blood cell precursors to suppress the production of sickle hemoglobin.
The therapy then raises the levels of fetal hemoglobin to protect patients against disease progression.
BIVV003 is being developed as part of an exclusive agreement between Bioverativ and Sangamo to develop 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,” Ken Huttner, an MD and PhD, vice president of clinical development at Bioverativ, said in a press release.
“It represents our commitment to advancing cutting-edge science and offers hope to the many people who have been waiting generations for an effective way to treat sickle cell disease. We look forward to advancing the program into clinical trials,” he said.
The IND acceptance allows Bioverativ to begin a Phase 1/2 clinical trial designed to assess the safety, tolerability, and effectiveness of BIVV003 in adults with sickle cell disease.
In this trial, patients’ hematopoietic stem cells (HSCs) will be isolated from blood drawn and then engineered with gene-editing techniques using ZFNs to modify a part of the BCL11A gene.
After a bone marrow conditioning regimen, their own modifed HSCs will be infused back into the patients to start producing red blood cells that have an increased ability to produce fetal hemoglobin.
The approach uses the patients’ cells to reduce the risk of graft failure and eliminate the risk of graft-versus-host disease, as well as the need for immunosuppression that is associated with donor transplants.
Bioverativ expects to open several clinical sites in the U.S. in 2018.
“Sickle cell disease is a lifelong blood disorder with serious, painful and debilitating complications, and patients deserve new, more effective treatment options,” said 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,” he said. “We believe the precision, efficiency, and specificity of zinc finger nuclease technology differentiate BIVV003 from other genomic therapies in development.”
Sangamo is now enrolling participants with transfusion-dependent beta-thalassemia in a Phase 1/2 trial (NCT03432364) to evaluate the safety, tolerability, and efficacy of ST-400, an experimental therapy that uses the same gene-editing approach as BIVV003.
In the United States, sickle cell disease is estimated to affect nearly 100,000 people.