Sangamo BioSciences, Inc. Drug SB-509 Fails Midstage Study
Sangamo management will host a conference call at 5:00 p.m. ET today to review these data and the ongoing clinical studies supporting the development of SB-509.
"Our first Phase 2 study, SB-509-601, had three goals," stated Dale Ando, M.D., Sangamo's vice president, therapeutic development and CMO. "First, we wanted to determine the safety of repeat dosing. Second, we evaluated dose schedule, specifically whether a regimen of three administrations of the maximum dose given at two month intervals would be more effective than a single administration. Finally, we hoped to gain clarity around clinical endpoints for use in the design of future studies. While this study has not added to our data around the most suitable end-points or dosing schedule for a Phase 3 trial, it has demonstrated that the drug continues to have an excellent safety profile. This is valuable information for our future development efforts."
"We also know that SB-509 is an active agent. We have positive preclinical data in several animal models of angiogenesis and nerve injury. We also have impressive data from our prior Phase 1 clinical study, SB-509-401, with a single treatment in the same patient population. In addition, we have encouraging positive interim data in our SB-509-701A study in which we are assessing recovery of nerve conduction velocity (NCV) in subjects with moderate to severe DN after two treatments with SB-509. Recovery of NCV in this more severe population that presents with "blocked" nerves or nerves with unmeasurable NCVs provides a binary outcome. The SB-509-701A trial is nearly complete and we expect to have more data from this study in the first quarter of 2009."
"The results from the SB-509-601 study are certainly unexpected," stated Edward Lanphier, Sangamo's president and CEO. "The data that we obtained on measures of nerve health and function are quite different than what we observed in our Phase 1b study. However, the 601 trial is only one part of our broad clinical development program to evaluate SB-509 which we will continue to prosecute. Based on our positive Phase 1b clinical data and encouraging interim data from our Phase 2 repeat-dosing study (SB-509-701A) in subjects with moderate to severe DN, we continue to have a high degree of confidence in this drug."
Conference Call
Sangamo will host a conference call today, November 10, 2008 at 5:00 p.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 888-690-2875 for domestic callers and 913-981-5543 for international callers. The passcode for the call is 2585543. 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 8:00 p.m. ET on November 10, 2008 to midnight, Monday November 17, 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 2585543.
About SB-509
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 Mild to Moderate DN (SB-509-601)
The study is a double-blind, placebo-controlled, repeat-dosing multi- center study designed to evaluate the clinical safety and clinical effects of repeat administration of SB-509 in diabetics with mild to moderate diabetic peripheral sensory motor neuropathy in the legs.
110 subjects were enrolled into the trial. Subjects were randomized to one of two groups. The larger group was treated by intramuscular injection of 60 mg of SB-509 (30 mg of SB-509 per leg) into the lower limb every two months. The remaining group received an equal volume of placebo on the same schedule. Each subject received a total of three treatments (Day 0, 60 and 120). Subjects received injections in a distribution pattern that targets the major peripheral nerves in the legs and feet.
The symptoms of diabetic peripheral neuropathy and any changes that occur during the trial were evaluated based on neurological examination data, electrophysiological testing data, subject neurological questionnaire, and subject pain assessment. Specifically, investigators used the following tests: the visual analog scale for pain intensity (VASPI), a modified Neuropathy Impairment Score -- Lower Limbs (NIS-LL) scoring system as well as total neuropathy score (TNS) to assess signs and symptoms of the condition. In addition, data from electrophysiological testing using nerve conduction velocity (NCV) to assess the rate at which a nerve can conduct an electrical signal, and quantitative sensory testing (QST) with the Vibratron II instrument, to assess the threshold of detection of vibration were also collected. Skin biopsies were taken to evaluate the direct therapeutic effect of SB-509 on nerve regrowth.
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.
About Sangamo
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.
Source: Sangamo BioSciences, Inc.