FDA Agrees to Phase 1 Trial of ET3, Gene Therapy for Hemophilia A

Joana Carvalho, PhD avatar

by Joana Carvalho, PhD |

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The U.S. Food and Drug Administration (FDA) has approved Expression Therapeutics‘ request to open a Phase 1 trial of ET3, an investigational gene therapy for people with hemophilia A.

The decision followed a review of the company’s investigational new drug application (IND) requesting clearance of ET3 for clinical testing.

Patient enrollment in the Phase 1 trial, called ET3-201, is expected to start soon at Emory University.

“We are extremely pleased that the FDA has granted permission to proceed with this clinical study,” Trent Spencer, PhD, president of Expression Therapeutics and director of the Cell and Gene Therapy Program in the Aflac Cancer and Blood Disorders Center at Emory, said in a press release.

ET3 is an investigational gene therapy that uses genetically modified blood cell progenitors, called hematopoietic stem cells, derived from patients’ white blood cells.

Investigators use a recombinant (man-made) lentiviral vector to force blood cell progenitors to produce an altered version of factor VIII (FVIII), the clotting protein that is missing in people with hemophilia A. The modified cells are then returned to patients, so that they may generate new blood cells able to produce a functional form of FVIII.

High levels of the modified FVIII driven by the gene therapy are expected to improve blood clotting and prevent spontaneous bleeds in people with hemophilia A.

According to the company, the combined use of stem cells and lentiviral-based gene therapy is the only therapeutic approach now available that may be a cure for both adults and children with hemophilia A.

During the ET3-201 trial, patients will first be treated at low-dose agents that suppress stem and immune cells, followed by a single intravenous infusion (directly into the bloodstream) of ET3. Once given, this experimental therapy is expected to remain active throughout a person’s lifetime.

“We are very excited to get the hemophilia A clinical trial underway, the first of six gene therapy products currently under development at Expression Therapeutics,” said Mohan Rao, PhD, the company’s CEO.

In addition to ET3, the Atlanta-based company is developing gene therapies for diseases that include hemophilia B, hemophagocytic lymphohistiocytosis (HLH), acute myeloid leukemia (AML), T-cell lymphoma and leukemia, and neuroblastoma.