Sangamos’s molecular technology enables a patient’s liver to produce an enduring and stable supply of factor IX (FIX), a clotting protein that’s defective or missing in hemophilia B.
Given through a single injection, SB-FIX is made up of engineered zinc finger nucleases (ZFNs) — the most abundant DNA binding proteins in the body that act as “molecular scissors” —, human FIX and adeno-associated virus (AAV) vectors. AAV vectors do not cause any disease and are capable of invading living cells, making them perfect DNA delivery vehicles.
SB-FIX was designed to deliver the correct copy of the FIX gene in the DNA of liver cells. The ZFNs in SB-FIX were “biologically modified” to cut the DNA sequence in a specific location of the albumin gene upon entering liver cells, allowing for the insertion of FIX’s correct copy in the cellular genome.
Although only a small portion of these cells will take up the engineered gene, the liver will be able to produce functionally active FIX and secrete it into the bloodstream, subsequently treating the disease.
In this open-label, non-randomized, ascending dose Phase 1/2 clinical trial (NCT02695160), 12 patients with severe hemophilia B will receive a low, medium or high dose of SB-FIX to evaluate the therapy’s safety, tolerability and preliminary effectiveness.
Therapy-related adverse side effects will be assessed for a 36-month period after SB-FIX infusion, as a primary goal. Secondary goals include change from baseline in FIX antigen (a molecule that induces an immune response) and activity levels, plus presence of parts of the SB-FIX molecular complex in plasma, saliva, urine, stool and semen.
“I am grateful to the first patient entering this study as we explore the symbolic step toward potentially changing what treatment could look like for patients with hemophilia B,” Craig Kessler, MD, said in a press release. Kessler is a professor of oncology at Georgetown University, director of the Center for Comprehensive Hemophilia and Thrombosis Care, and this study’s investigator.
“This clinical trial will generate data highly anticipated by scientists, physicians and patients, and we are honored to be the first medical center to treat a patient.”
The U.S. Food and Drug Administration (FDA) granted SB-FIX orphan drug and fast track designations in 2016 and 2017, respectively. In 2018’s first trimester, the Medicines and Healthcare Products Regulatory Agency (MHRA) granted clinical trial authorization (CTA) in the U.K. Importantly, this British CTA allows assessment of SB-FIX in not only adults, but also in patients older than 12.
“We are excited to begin to understand the potential of our in vivo gene editing technology for hemophilia B, which represents a completely new treatment approach for this disease,” said Sangamo’s chief medical officer, Edward Conner, MD.