Injection site reactionswere the most common adverse events reported and were mild and reversible.Importantly, subjects in the study were treated within the pharmacologicallyeffective dose range that was demonstrated to be efficacious in preclinicalanimal studies.
'Although the primary end-point of the SB-509-401 study was safety, wealso observed statistically significant and clinically relevant improvementsin a number of quantitative measures of neurological health,' said EdwardLanphier, Sangamo's president and CEO. 'We believe that SB-509 represents anew therapeutic approach for diabetic neuropathy, designed to directly protectand possibly restore nerve function, in contrast to the current standard ofcare designed to address the pain associated with this condition. We areencouraged by the data so far and are swiftly moving forward to the next stageof clinical development with our ongoing Phase 2 clinical trials. We expectto have data from our double blind Phase 2 clinical trial (SB-509-601)available in the fourth quarter of this year.'
About SB-509
SB-509 is an injectable formulation of a plasmid encoding a zinc fingerDNA-binding protein transcription factor (ZFP TF(TM)) designed to upregulatethe expression of the gene encoding vascular endothelial growth factor(VEGF-A). VEGF-A has been demonstrated to have direct neurotrophic andneuroprotective properties. In preclinical animal efficacy studies in adiabetic rat model (Diabetes, June 1, 2006; 55(6): 1847-1854), SB-509 hasproven effective in protecting motor and sensory nerve function fromdisease-induced nerve damage.
About the SB-509 Clinical Program
Sangamo has three ongoing Phase 2 studies in diabetics with sensory/motorneuropathy:
Phase 2 study of SB-509 for mild to moderate DN (SB-509-601)
The clinical trial is a double-blind, placebo-controlled, repeat-dosingstudy designed to evaluate the clinical safety and clinical effects of repeatadministration of SB-509 in diabetics with mild to moderate diabeticperipheral sensory motor neuropathy in the legs. The trial is being conductedat multiple sites and is fully enrolled; data is expected to be available inthe fourth quarter of 2008.
Approximately 100 subjects have been enrolled into the trial. Subjectshave been randomized to one of two groups in a 2:1 ratio. The larger group(approximately 66 subjects) will be treated by intramuscular injection of 60mg of SB-509 (30 mg of SB-509 per leg) into the lower limb every 2 months.The remaining group (approximately 33 subjects) will receive an equal volumeof placebo on the same schedule. Each subject will receive a total of threetreatments (Day 0, 60 and 120). Subjects will receive injections in adistribution pattern that targets the major peripheral nerves in the legs andfeet.
The symptoms of diabetic peripheral neuropathy and any changes that occurduring the trial will be evaluated based on neurological examination data,electrophysiological testing data, subject neurological questionnaire, andsubject pain assessment. Specifically, investigators will use the followingtests: the visual analog scale for pain intensity (VASPI), a modifiedNeuropathy Impairment Score - Lower Limbs (NIS-LL) scoring system as well astotal neuropathy score (TNS) to assess signs and symptoms of the condition. Aquantitative neurologic exam such as NIS-LL is widely regarded by neurologistsas the most comprehensive approach to evaluating changes in nerve health. Inaddition, data from electrophysiological testing using nerve conductionvelocity (NCV) to assess the rate at which a nerve can conduct an electricalsignal, and quantitative sensory testing (QST) with the Vibratron IIinstrument, to assess the threshold of detection of vibration are also beingcollected. Skin biopsies will also be taken to evaluate the direct therapeuticeffect of SB-509 on nerve regrowth. This test is a very sensitive marker ofDN severity and may provide an important mechanistic marker for efficacy.
Phase 2 study of SB-509 for moderate to severe DN (SB-509-701)
The clinical trial is a single-blind, placebo-controlled, repeat-dosingstudy designed to evaluate the clinical safety and clinical effects of repeatadministration of SB-509 in diabetics with moderate to severe diabeticperipheral sensory motor neuropathy in the legs. The trial is being conductedat multiple sites, accrual has been completed and plans recently announced toexpand the study and enroll additional subjects.
In the initial trial, 45 subjects have completed enrollment. Subjectswere randomized to one of two groups in a 2:1 ratio. The larger group(approximately 30 subjects) was treated by intramuscular injection of 60 mg ofSB-509 (30 mg of SB-509 per leg) into the lower limb and will be treated every3 months. The remaining group (approximately 15 subjects) received an equalvolume of placebo on the same schedule. Each subject will receive a total oftwo treatments (Day 0 and 90). Subjects receive injections in a distributionpattern that targets the major peripheral nerves in the legs and feet.
As announced on June 6, 2008, Sangamo will expand the Phase 2 study byenrolling approximately 45 additional subjects in the trial. Subjects willagain be randomized to one of two groups in a 2:1 ratio. The larger group(approximately 30 subjects) will be treated by intramuscular injection of 60mg of SB-509 (30 mg of SB-509 per leg) into the lower limb every 2 months.The remaining group (approximately 15 subjects) will receive an equal volumeof placebo on the same schedule. Each subject will receive a total of threetreatments (Day 0, 60 and 120).
