Approval from the U.K.’s Medicines and Healthcare Products Regulatory Agency (MHRA) will make this the first genome-editing study conducted in Europe.
Once safety and efficacy data have been obtained in adult hemophilia B patients, Sangamo will begin enrolling adolescents (ages 12 to 17) in the U.K, which the company plans for later this year. The open-label trial (NCT02695160) is already recruiting adults in the U.S. Enrollment is estimated at 12 patients.
Participants, who will receive ascending doses of SB-FIX, will be divided into three groups to test a low, medium, and high dose. The primary objective is to assess the therapy’s safety and tolerability for up to 36 months after the SB-FIX infusion. Researchers will also evaluate changes from the start of treatment in FIX antigen and activity levels.
SB-FIX is part of Sangamo’s zinc finger nucleases (ZFNs) approach. ZFNs are naturally occurring proteins that act as molecular scissors by cutting through DNA sequences, working as a genome-editing strategy. These proteins can be engineered to target any DNA sequence. The cell’s repair machinery then fixes the break, and the strategy can be used to insert therapeutic genes into the human genome.
Hemophilia B is caused by a missing or defective factor IX (FIX), a clotting protein. SB-FIX was designed to provide stable production of FIX throughout a patient’s lifetime.
The potential therapy works by introducing the corrective gene into the DNA of liver cells. SB-FIX is delivered in a single intravenous infusion using adeno-associated viral vectors (AAVs) targeting the liver. AAVs are modified, non-infectious viruses, commonly used in gene therapy.
The ZFNs contain DNA instructions that can only be “unlocked” by liver cells. Upon entering the cells, ZFNs cut the DNA in a specific spot in the albumin gene, which enables the insertion of the corrective FIX gene.
Compared with other gene therapy approaches, Sangamo claims its ZFN-based strategy enables superior precision and duration of treatment.
In 2016, SB-FIX received orphan drug status by the U.S. Food and Drug Administration (FDA) to speed its development for hemophilia B patients.
“Patients with hemophilia B need improved treatment options, and we are pleased to have rapidly reached agreement with the MHRA to expand the SB-FIX clinical trial to sites in the United Kingdom,” Edward Conner, MD, Sangamo’s chief medical officer, said in a press release.
“In vivo genome editing aims to provide a life-long therapeutic solution for certain genetic diseases,” he said.
He added that Sangamo ultimately plans to conduct clinical studies in children: “We believe the greatest value for this approach is in the treatment of children, and our goal with this study is to accumulate safety and efficacy data supporting progression of clinical trials into younger patient populations.”
Besides this trial for hemophilia B, the company will also seek regulatory approval to start clinical studies in SB-318 and SB-913, which are additional genome-editing treatment candidates for mucopolysaccharidosis type I and II, respectively.