RICHMOND, Calif., Nov. 15, 2013 /PRNewswire/ -- Sangamo BioSciences, Inc. (NASDAQ: SGMO) announced today the presentation of positive data from the Phase 1 clinical trial of CERE-110 (AAV-NGF), a gene therapy approach designed to deliver nerve growth factor (NGF) for the treatment of Alzheimer's disease (AD). This novel product was developed by Ceregene, Inc., which was recently acquired by Sangamo. The data were presented at the Sixth Clinical Trials on Alzheimer's Disease (CTAD) Meeting, which is being held in San Diego from November 14-16, 2013.
The data from this dose escalation study demonstrate that surgical delivery of CERE-110 to the brain results in the long-term expression of bioactive NGF, the therapeutic protein. Clinicians also observed apparent stabilization of brain cell metabolic activity in treated subjects, as determined by PET-scans measuring glucose use, which may reflect a slowing of cell deterioration. The treatment was well-tolerated at all dose levels.
"These early clinical data demonstrate that this therapeutic approach is feasible, well-tolerated and results in appropriate delivery of the therapeutic, NGF protein, to the intended target cells in the brain," said Paul Aisen, M.D., Project Director of the ongoing Phase 2 clinical trial of CERE-110 and director of the Alzheimer's Disease Cooperative Study (ADCS) at the University of California San Diego, a preeminent research consortium for testing new treatments for Alzheimer's disease. "We are very pleased to be involved in the Phase 2 clinical trial, which is a placebo-controlled study, and will enable further evaluation of the efficacy of CERE-110. Alzheimer's disease has few effective treatment options, and this therapy could help the over five million people in the U.S. currently living with the disease."
The Phase 2 clinical study of CERE-110 is being carried out in collaboration with the ADCS and is funded by a grant from the National Institute on Aging (NIA), part of the National Institutes of Health (NIH).
"We are very encouraged by the Phase 1 data from the CERE-110 study," stated Edward Lanphier, Sangamo's president and CEO. "These positive data supported the further testing of this novel approach in a Phase 2 clinical trial to evaluate efficacy. The Phase 2 study is fully-funded and fully-enrolled and currently in the two year follow-up phase. We look forward to presenting data from the clinical trial in 2015."
The data, which have been accepted for publication in Alzheimer's and Dementia, the official publication of The Alzheimer's Association (Rafii et al., 2013), were presented by Raymond Bartus, Ph.D., who led the preclinical and early clinical development of CERE-110.
It is well-documented that cholinergic nerve cells in the brain degenerate early in AD and are linked to initial memory loss and cognitive decline. Current therapies for AD include a class of small molecule drugs called cholinesterase inhibitors, which aim to preserve or enhance the chemical signaling in cholinergic nerves. However, these drugs have dose-limiting side-effects, do not change the underlying disease process or its progression, are effective for some but not all people, and may help only for a limited time.
Research in animal models suggests that growth factors, such as NGF, which promote nerve growth, nerve repair and protect nerves against damage, may improve AD symptoms and slow disease progression. However, delivery of proteins to the appropriate part of the brain, in a manner that enables them to have a therapeutic effect, has proved challenging due to the blood brain barrier. Gene therapy with AAV, combined with stereotactic surgery, enables delivery of the gene encoding a biologically active protein such as NGF to a precise location in the brain. The nucleus basalis of Meynert (NBM), a structure near the base of the brain, is considered to be the best target for delivery of a gene-based therapeutic for AD as its cells represent the primary source of cholinergic nerves projecting to the brain cortex. Thus, a single treatment of CERE-110 into this structure is expected to provide a safe long-term source of NGF protein that may protect and preserve cholinergic cells in the brains of AD patients and potentially slow disease progression.
About the CERE-110 Phase 1 Study and Summary of Data Presented at the CTAD Meeting
Ten subjects (10) with mild to moderate AD were treated with a single administration of CERE-110 in an open-label dose-escalation study to evaluate three different doses of the therapeutic (two dose cohorts of three subjects each and the third, highest dose, of four subjects). The drug was delivered by standard stereotactic surgery into the NBM and subjects were followed for 24 months. The trial was designed to evaluate safety and tolerability, and signs of efficacy.
The data demonstrated that:
- The treatment is feasible and well tolerated. Serious adverse events (SAEs) were transient, acceptable and related to the surgical procedure. AEs were not dose-related and not related to either the AAV or NGF
- Long term expression of NGF was observed in brain tissue, with desired changes in neuronal cell volume of targeted neurons providing evidence of bioactivity
- Preservation of glucose utilization, as measured by 18FDG (Fludeoxglucose) Positron Emission Tomography (PET) brain imaging, was observed through the 24 months of the study suggesting that the nerve cells of the brain were not deteriorating significantly over this time period
- Efficacy assessments such as mental state (MMSE), cognition (ADAS-Cog) and activities of daily living (ADAS-ADL), demonstrated no evidence of accelerated decline over 24 months, although the sample size was too small to allow any conclusions to be drawn regarding improvement in symptoms.
About the Ongoing CERE-110 Phase 2 Study
Forty-nine (49) patients with mild to moderate AD were treated with a single administration of CERE-110 at 10 clinical sites throughout the U.S. Approximately half of the patients received CERE-110 while the other half received an appropriate sham (placebo) surgery control treatment. Patients will be followed for a minimum of two years with respect to safety, brain imaging, as well as measures of cognitive function and quality of life - standard tests used in Alzheimer's clinical trials. The clinical study was carried out in collaboration with the Alzheimer's Disease Cooperative Study (ADCS) based at the University of California San Diego (UCSD) and funded by a grant from the National Institute on Aging (NIA). Enrollment was completed in March 2013 and data are expected in 2015.
CERE-110 is an adeno-associated viral (AAV) vector that encodes the gene for nerve growth factor (NGF), a naturally occurring protein that maintains survival of nerve cells in the brain. CERE-110 is surgically injected into the nucleus basalis of Meynert (NBM), a brain region where cholinergic nerve cell degeneration occurs in AD. Delivery of NGF using an AAV vector has the potential to induce sustained expression of NGF, resulting in long-lasting protection and preservation of cholinergic nerves. The cholinergic system is important in memory and cognitive function, and a restoration of the function of this system may slow the progression of the disease and possibly improve memory in individuals with AD.
About Alzheimer's Disease (AD)
Alzheimer's disease is a progressive disorder of the brain that gradually affects one's memory and ability to learn, reason, communicate and carry out daily activities. There are now more than five million people in the United States living with AD, and there is currently no cure.
Since 2008, CTAD has been a conference organized and planned by AD clinical researchers for AD clinical researchers. CTAD embraces the organizing committee mandate to maintain CTAD's unique role in AD research: To provide a substantive, clinical research-oriented conference and an annual opportunity for the world's preeminent clinical researchers to engage in both formal and informal exchanges of views. CTAD's ongoing commitment to providing a relatively intimate forum has resulted in the conference's reputation of facilitating and fostering international collaboration in AD clinical research matters. More information is available at www.ctad-alzheimer.com.
Sangamo BioSciences, Inc. is focused on research and development of novel DNA-binding proteins for therapeutic gene regulation and genome editing. The Company has ongoing Phase 2 and Phase1/2 clinical trials to evaluate the safety and efficacy of a novel ZFP Therapeutic® for the treatment of HIV/AIDS. As part of its acquisition of Ceregene Inc., Sangamo acquired a fully-enrolled and funded, double-blind, placebo-controlled Phase 2 trial to evaluate NGF-AAV (CERE-110) in Alzheimer's disease. Sangamo's other therapeutic programs are focused on monogenic diseases, including hemophilia, Huntington's disease and hemoglobinopathies such as beta-thalassemia and sickle cell anemia. Sangamo's core competencies enable the engineering of a class of DNA-binding proteins known as zinc finger DNA-binding proteins (ZFPs). Engineering of ZFPs that recognize a specific DNA sequence enables the creation of sequence-specific ZFP Nucleases (ZFNs) for gene modification and ZFP transcription factors (ZFP TFs) that can control gene expression and, consequently, cell function. Sangamo has entered into a strategic collaboration with Shire to develop therapeutics for hemophilia, Huntington's disease and other monogenic diseases and has established strategic partnerships with companies in non-therapeutic applications of its technology including Dow AgroSciences and Sigma-Aldrich Corporation. For more information about Sangamo, visit the company's website at www.sangamo.com
ZFP Therapeutic® is a registered trademark of Sangamo BioSciences, Inc.
This press release may contain forward-looking statements based on Sangamo's current expectations. These forward-looking statements include, without limitation, references relating to the development of CERE-110 for the treatment of Alzheimer's disease and expected timing of data release from the CERE-110 Phase 2 clinical trial. 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 our clinical trials, whether the clinical trials will validate and support the tolerability and efficacy of CERE-110, ZFNs and ZFP TFs, technological challenges, Sangamo's ability to develop commercially viable products and technological developments by our competitors. For a more detailed discussion of these and other risks, please see Sangamo's public filings with the Securities and Exchange Commission, including the risk factors described in its Annual Report on Form 10-K and its most recent Quarterly Report on Form 10-Q. Sangamo assumes no obligation to update the forward-looking information contained in this press release.
SOURCE Sangamo BioSciences, Inc.