Sangamo BioSciences Announces Presentation of Data From Diabetic Neuropathy Clinical Trials
Positive Interim Data from Ongoing SB-509-701 Study in Subjects with Moderate to Severe Diabetic Neuropathy and Additional Data from Phase 1b Clinical Trial SB-509-401
RICHMOND, Calif., Sept. 15 /PRNewswire-FirstCall/ -- Sangamo BioSciences, Inc. announced today the presentation of positive interim Phase 2 clinical data from its ZFP Therapeutic(TM) program (SB-509-701) at the International Society for Cellular Therapy (ISCT) Europe Regional Meeting in Antwerp, Belgium. The data presented demonstrate an improvement in nerve conduction velocity (NCV) in SB-509 treated subjects with moderate to severe diabetic neuropathy (DN), a patient population that until now has been considered impossible to treat.
Sangamo management will host a conference call at 11:00 a.m. ET today to discuss these data.
In addition, on September 8, 2008, new data were presented from Sangamo's Phase 1b study (SB-509-401) at the 44th Annual Meeting of the European Association for the Study of Diabetes (EASD) demonstrating a statistically significant (p= 0.0016) positive correlation of 2 or more response endpoints in the SB-509 treated group compared with placebo treated subjects at day 180 post-treatment. Response endpoints were defined as greater than a 14% improvement in quantitative sensory testing (QST), greater than 0.8 meters/second (m/sec) improvement in NCV and greater than a 3 point improvement as judged by the Neuropathy Impairment Scale -- Lower Limbs (NIS-LL). Data have previously been presented from this trial demonstrating a statistically significant improvement in NIS-LL and QST and trends for improvement in NCV. Sangamo has a larger, repeat-dosing clinical trial (SB-509-601) in this population of subjects with mild to moderate DN.
Data presented today at ISCT from the study SB-509-701 were collected from subjects with moderate to severe diabetic peripheral neuropathy. All subjects entered the trial with between one and six nerves in the lower limb that were "blocked" or for which no NCV could be measured. The majority of the subjects had at least one blocked sural nerve, the most relevant in DN. Subjects received two treatments in both legs of either placebo (n=10 subjects) or SB-509 (n=17) (60 mg total dose, 30 mg per leg) one at Day 0 and one at Day 90. Recovery of NCV during 180 days post treatment in subjects who entered the trial with blocked sural nerves was observed in 75% of the SB-509-treated subjects compared to 25% of the placebo-treated group. SB-509 was well tolerated and no drug-related severe adverse events were observed.
"While these are interim data, we are very pleased and excited by the return of NCV in such a high percentage of these subjects," commented Dale Ando, M.D., Sangamo's vice president, therapeutic development and CMO. "This is a patient population for which historically there have been absolutely no treatment options. This sural nerve recovery data in subjects in the Phase 2 study reinforces our preliminary and surprising data in 3 subjects in the Phase 1 trial.
The sural nerve on the foot is a sensory nerve and one of the first nerves to be affected as diabetic neuropathy progresses. However, some of the subjects enrolled in this study had quite severe neuropathy with all six nerves of the nerves that we are monitoring blocked. Not surprisingly, we found that subjects entering the study with fewer blocked nerves showed the highest rates of response to these two treatments with SB-509.
When we began this trial we chose a more conservative two dose regimen as this is a sicker population than that originally tested in the Phase 1b study. The data suggest that two doses are well tolerated and that our observations from the Phase 1 trial were worth pursuing. We have expanded the trial to include a third treatment with SB-509 and believe that the increased dose and increased subject numbers will provide us with valuable information in determining how well more severely affected DN patients will respond."
A total of 45 subjects have been enrolled in the trial (SB-509-701) who were randomized to one of two groups in a 2:1 ratio and received 2 treatments at (Day 0 and Day 90). The trial has also been expanded to include a further 45 subjects randomized in the same ratio who will receive three treatments (Day 0, Day 60 and Day 120), the same dosing schedule as that used in Sangamo's Phase 2 trial of SB-509 in subjects with mild to moderate DN (SB-509-601).
"While these data are from a relatively small number of subjects, we are very encouraged by the safety of SB-509 in a repeat dosing situation and the greater evidence for clear improvements that are unprecedented in this moderate to severe DN population," said Edward Lanphier, Sangamo's president and CEO. "SB-509 is designed to address nerve damage and these data demonstrate that SB-509 may have both a neuroprotective and a neuroregenerative effect and confirm earlier analyses which showed similar trends. Based on these data and data from our Phase 1b study we expanded the SB-509-701 trial. Additional data from this expanded trial may provide important information which could expedite the design of a Phase 3 study. We also look forward to presenting data from our double blind Phase 2 clinical trial (SB-509-601) later this year."
Sangamo will host a conference call today, September 15, 2008, 2008 at 11:00 a.m. ET, which will be open to the public. The call will also be webcast live and can be accessed via a link on the Sangamo BioSciences website in the Investor Relations section under "Events and Presentations" http://investor.sangamo.com/events.cfm . The webcast replay will also be available for two weeks after the call. During the conference call, the company will review the data presented today.
The conference call dial-in numbers are 877-719-9810 for domestic callers and 719-325-4751 for international callers. The passcode for the call is 4708168. For those unable to listen in at the designated time, a conference call replay will be available for one week following the conference call, from approximately 2:00 p.m. ET on September 15, 2008 to midnight, Monday September 22, 2008. The conference call replay numbers for domestic and international callers are 888-203-1112 and 719-457-0820, respectively. The conference ID number for the replay is 4708168.
SB-509 is an injectable formulation of a plasmid encoding a zinc finger DNA-binding protein transcription factor (ZFP TF(TM)) designed to upregulate the expression of the gene encoding vascular endothelial growth factor (VEGF-A). VEGF-A has been demonstrated to have direct neurotrophic and neuroprotective properties. In preclinical animal efficacy studies in a diabetic rat model (Diabetes, June 1, 2006; 55(6): 1847-1854), SB-509 has proven effective in protecting motor and sensory nerve function from disease-induced nerve damage.
Phase 2 study of SB-509 for moderate to severe DN (SB-509-701)
The clinical trial is a single-blind, placebo-controlled, repeat-dosing study designed to evaluate the clinical safety and clinical effects of repeat administration of SB-509 in diabetics with moderate to severe diabetic peripheral sensory motor neuropathy in the legs. The trial is being conducted at multiple sites, accrual has been completed and plans recently announced to expand the study and enroll additional subjects.
Accrual of the first part (Part A) of SB-509-701 is complete with 45 subjects enrolled who were 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 of SB-509 (30 mg of SB-509 per leg) into the lower limb and will be treated every 3 months. The remaining group (approximately 15 subjects) received an equal volume of placebo on the same schedule. Each subject will receive a total of two treatments (Day 0 and 90). Subjects receive injections in a distribution pattern that targets the major peripheral nerves in the legs and feet.
As announced on June 6, 2008, Sangamo will expand the Phase 2 study by enrolling approximately 45 additional subjects in the trial (Part B). Subjects will again 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 60 mg 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 volume of placebo on the same schedule. Each subject will receive a total of three treatments (Day 0, 60 and 120). Subjects will receive injections in the same pattern used in the initial part of the trial.
The symptoms of diabetic peripheral neuropathy and any changes that occur during the trial will be evaluated based on neurological examination data, electrophysiological testing data, subject neurological questionnaire, and subject pain assessment. Specifically, investigators will measure NCV, will assess pain using VASPI, and use scoring systems such as a modified NIS-LL and TNS to quantify neurologic exam and assess signs and symptoms of the condition.
For each subject the trial is expected to take approximately fourteen months: two months for screening, three months for subject treatment and a further nine months for subject follow-up. Individuals interested in participating in this trial should visit http://www.clinicaltrials.gov/ .
About Diabetic Neuropathy
Diabetic peripheral neuropathy is one of the most frequent complications of diabetes. Symptoms include numbness, tingling sensations and pain particularly in the toes or feet. This gradually evolves to loss of sensation and motor function as nerve damage progresses. Ulcers and sores may appear on numb areas of the foot because pressure or injury goes unnoticed. Despite adequate treatment, these areas of trauma frequently become infected and this infection may spread to the bone, necessitating amputation of the leg or foot. More than 60 percent of non-traumatic lower-limb amputations in the United States occur among people with diabetes. In 2004, this translated to approximately 71,000 amputations. Diabetes is a growing problem, the Centers for Disease Control estimates that from 1980 through 2007, the number of Americans with diabetes increased from 5.6 million to 23.6 million and that of those about 60 percent to 70 percent have mild to severe forms of neuropathy.
Sangamo BioSciences, Inc. is focused on the research and development of novel DNA-binding proteins for therapeutic gene regulation and modification. The most advanced ZFP Therapeutic(TM) development program is currently in Phase 2 clinical trials for evaluation of safety and clinical effect in patients with diabetic neuropathy and ALS. Other therapeutic development programs are focused on cancer, HIV/AIDS, neuropathic pain, nerve regeneration, Parkinson's disease and monogenic diseases. Sangamo's core competencies enable the engineering of a class of DNA-binding proteins known as zinc finger DNA-binding proteins (ZFPs). By engineering ZFPs that recognize a specific DNA sequence Sangamo has created ZFP transcription factors (ZFP TF(TM)) that can control gene expression and, consequently, cell function. Sangamo is also developing sequence-specific ZFP Nucleases (ZFN(TM)) for gene modification. Sangamo has established strategic partnerships with companies outside of the human therapeutic space including Dow AgroSciences, Sigma-Aldrich Corporation and several companies applying its ZFP Technology to enhance the production of protein pharmaceuticals. For more information about Sangamo, visit the company's web site at http://www.sangamo.com.
This press release may contain forward-looking statements based on Sangamo's current expectations. These forward-looking statements include, without limitation, references to the clinical trials of SB-509, research and development of novel ZFP TFs and ZFNs and therapeutic applications of Sangamo's ZFP technology platform. Actual results may differ materially from these forward-looking statements due to a number of factors, including uncertainties relating to the initiation and completion of stages of the SB-509 clinical trials, whether the SB-509 clinical trials will validate and support tolerability and efficacy of SB-509, technological challenges, Sangamo's ability to develop commercially viable products and technological developments by our competitors. See Sangamo's SEC filings, and in particular, the risk factors described in the it's Annual Report on Form 10-K and its most recent Quarterly Report on Form 10-Q. Sangamo BioSciences, Inc. assumes no obligation to update the forward-looking information contained in this press release.
CONTACT: Elizabeth Wolffe, Ph.D. of Sangamo BioSciences, Inc.,+1-510-970-6000, ext. 271, firstname.lastname@example.org
Web site: http://www.sangamo.com/
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Posted: September 2008