Duchenne muscular dystrophy (DMD) is a progressive, fatal neuromuscular disease caused by the absence of functional dystrophin protein in skeletal and cardiac muscle. SGT-001 is a systemically administered AAV9 microdystrophin gene therapy developed to deliver and express a shorter but functional form of dystrophin that uniquely includes the neuronal nitric oxide synthase (nNOS) binding domain. It is being evaluated for the treatment of DMD in the ongoing IGNITE DMD Phase I/II clinical trial. Following the administration of a low dose of 5E13 vg/kg to 3 subjects the dose was escalated, and all subsequent subjects have received SGT-001 at 2E14 vg/kg.
To date the most common treatment emergent adverse events were nausea, emesis, pyrexia, thrombocytopenia, and headache. Three subjects experienced SAEs associated with complement activation within the first weeks following dosing, which have all resolved without sequelae. No new drug-related safety findings have been reported in any of the patients, who collectively have post-dosing periods of more than 5 months up to approximately 4 years.
Data previously presented up to 1.5 years showed continued improvements in motor function, pulmonary function, and patient reported outcome measures (PROMs) in 2E14 vg/kg cohort subjects. In addition, biopsies collected from these subjects at 12-24 months post-dosing showed continued expression of microdystrophin, restored membrane localization of ?-sarcoglycan and nNOS, and only very mild active dystrophic pathology.
We now present data up to 2 years post-dosing demonstrating the durability of SGT-001 treatment effect. Among other findings, subjects receiving the 2E14 vg/kg dose maintained stabilization or improvement in motor function (North Star Ambulatory Assessment, 6-Minute Walk Test), pulmonary function (FVC % predicted), and PROMs (PODCI) compared against expected natural history declines.
These data continue to suggest the potential for SGT-001 to confer meaningful clinical benefit to patients with DMD.