Rare Daily Staff
Sangamo Therapeutics said interim data from a phase 1/2 study of its experimental genome editing therapy SB-913 said at 16 weeks after dosing, reductions in several biomarkers were seen in patients with MPS II, or Hunter Syndrome, a rare metabolic disorder that causes progressive damage to organs and impairs mental development.
Patients with MPS II, a lysosomal storage disorder, have a deficiency of an enzyme that is needed to breakdown carbohydrates. As a result, waste fragments accumulate within cells. Over time, this accumulation impairs function of organs throughout the body. Many people with MPS II receive enzyme replacement therapy, but within a day of treatment, the level of the enzyme they need drops to undetectable levels.
Sangamo is seeking to repair the faulty gene that results in MPS II with its gene editing technology to remove the faulty gene and insert a correct version of it in its place. The company is targeting liver cells and believes its approach will create a stable and lifelong supply of the enzyme the patient lacks.
SB-913, makes use of the company’s zinc finger nuclease genome editing technology to insert a corrective gene into a precise location in the DNA of liver cells. The ZFNs and the corrective gene are delivered in a single intravenous infusion using AAV vectors that target the liver. The ZFNs enter the cells as inactive DNA instructions in a format designed only for liver cells to unlock. Once “unlocked”, the ZFNs then identify, bind to and cut the DNA in a specific location within the albumin gene. Using the cells’ natural DNA repair processes, liver cells can then insert the corrective gene for the deficient enzyme at that precise location.
The CHAMPIONS study is the first evaluation of an in vivo genome editing treatment in humans. The clinical trial is evaluating three separate doses of SB-913 over a planned 36-month study period. Data presented at the 2018 Annual Symposium of the Society for the Study of Inborn Errors of Metabolism in Athens, Greece included early safety and efficacy results for Cohort 1 (low dose) and Cohort 2 (mid dose), with two patients enrolled in each. Enrollment and dosing of Cohort 3 (high dose, 5x the mid dose) was recently completed.
The data showed that patients in Cohort 2 at 16 weeks post-dosing, had mean reductions in total urinary GAGs (51 percent), dermatan sulfate (32 percent), and heparan sulfate (61 percent).
“We are encouraged by the safety and tolerability profile observed to date and by the GAG reductions at week 16 in Cohort 2. We have recently infused the two Cohort 3 patients at a dose that is five times higher than the mid-dose of Cohort 2, and we look forward to seeing those results,” said Edward Conner, Chief Medical Officer of Sangamo. “If longer-term data from this study continue to be positive, therapeutic genome editing has the potential to bring tremendous medical progress for MPS II and other monogenic diseases.”
In all subjects, administration of SB-913 was generally well-tolerated. There were no serious adverse events reported as related to SB-913. All adverse events were mild, resolved without treatment, and did not show evidence of dose dependence.
September 6, 2018
Photo: Edward Conner, Chief Medical Officer of Sangamo