Presentation Details Statistically Significant and Clinically Relevant Results for SB-509 in Development for Treatment of Diabetic Neuropathy
SAN FRANCISCO, June 8 /PRNewswire-FirstCall/ -- Sangamo BioSciences, Inc.(Nasdaq: SGMO) announced today the presentation of encouraging Phase 1bclinical data from its ZFP Therapeutic(TM) program at the 68th ScientificSessions of the American Diabetes Association (ADA). As disclosed in an oralpresentation entitled, 'Evidence of Neuroregeneration Using VascularEndothelial Growth Factor (VEGF) Zinc Finger Protein Activator (SB-509) inDiabetic Neuropathy: A Chronic Degenerative Polyneuropathy,' results ofSangamo's Phase 1b clinical trial (SB-509-401) demonstrated statisticallysignificant improvements in measurements of nerve health and function insubjects with diabetic neuropathy.
'We are excited by the clinically relevant magnitude of improvements thatwere observed in measurements of nerve health and function in subjects withmild to moderate diabetic neuropathy over the six month trial period after asingle administration of SB-509,' commented the presenter, Mark Kipnes, M.D.,lead investigator on the Phase 1 trial and an endocrinologist at the Diabetesand Glandular Disease Clinic, San Antonio, Texas. 'Analgesics andantidepressants designed to control pain symptoms are the only drugs currentlyapproved to treat this condition. In contrast, SB-509 is designed to addressthe actual nerve damage. These data demonstrate that SB-509 may have aneuroprotective and a neuroregenerative effect.'
The data presented at ADA were collected from subjects with mild tomoderate diabetic peripheral neuropathy enrolled in Sangamo's Phase 1b studyof SB-509 (SB-509-401). Subjects received a single treatment in both legs ofeither placebo (12 subjects) or SB-509 (12 subjects who received 60 mg totaldose, 30 mg per leg). All of the subjects completed 6-month follow-uptesting. SB-509 was well tolerated and no drug-related severe adverse eventswere observed. Clinically relevant and statistically significant improvementswere seen in neurologic examination using the Neurological Impairment Score -Lower Limbs (NIS-LL) and quantitative sensory testing (QST) which quantifiesperception of vibration. In addition, there was a trend towards improvementin nerve conduction velocity (NCV), a measure of the ability of a nerve totransmit an applied electrical signal, in both sensory and motor nerves.
Specifically, improvement in neurologic evaluation by NIS-LL inSB-509-treated subjects was measured as a statistically significant,clinically relevant improvement of 1.9 point change from baseline levelscompared to a 0.7 point worsening in the placebo group (a delta in NIS-LL of2.6, p=0.043). In addition, there was a 25.3% improvement in detection ofmechanical sensation compared to baseline, as measured by QST testing, inSB-509-treated patients compared to a 5.1% worsening in the placebo group (adelta in QST of 30.4%, p=0.02). The mean improvement in sensory (sural) NCVmeasurements 180 days post treatment was 1.2 Meters/sec with SB-509 treatmentcompared to -0.4 Meters/sec with placebo (a delta in NCV of 1.6 Meters/sec).The mean sum of improvement of all lower extremity motor NCV measurements 180days post treatment was 0.8 Meters/sec with SB-509 treatment compared to -0.9Meters/sec with placebo (a delta in NCV of 1.7 Meters/sec).
While the primary end-point of Sangamo's Phase 1b study (SB-509-401) wassafety, data were also collected that were designed to measure changes inneurological health. Quantitative sensory testing (QST) using the Vibratron IIis used as a method of assessing a subject's change in vibration sensitivity.Direct measurement of the speed and amplitude of an applied electrical impulseor nerve conduction velocity (NCV) in both sensory and motor nerves is amethod of assessing the integrity or health of the nerve. A broader approachto quantification of clinical benefit involves the use of one of the manyavailable composite scoring systems. These include the Total Neuropathy Score(TNS) and the narrower Neuropathy Impairment Score in the Lower Limbs(NIS-LL). The NIS-LL is a validated instrument that can be used to measure aclinically meaningful change in the neurological status of patients with DNover time. NIS-LL includes measures of motor and sensory nerve heath as wellas reflex testing and is a quantifiable score of neurologic exam. These threemeasurements have all been used as primary or secondary endpoints of clinicalbenefit in Phase 3 studies.
'We are very encouraged by the safety of SB-509 and the improvements thatwe have seen in subjects with mild to moderate DN up to six-months afteradministration of a single dose of SB-509,' stated Dale Ando, M.D., Sangamo'svice president of therapeutic development and chief medical officer.'Particularly interesting are the encouraging and correlative gains observedin the NIS-LL and QST measurements of treated subjects which are independentand confirmatory. Both NIS-LL and QST have been used as end-points inprevious pivotal large scale trials of other non-analgesic approaches fordiabetic neuropathy. '
From a safety perspective, the Phase 1b data were consistent with previousobservations that a single treatment of SB-509 was well tolerated and that nodrug-related severe adverse events were observed.
