Neuralstem's NSI-189 Novel Neurogenic Compound Shows Significant Effect In Major Depressive Disorder Cognitive Deficit and Depression Symptoms Improve Significantly, Trial Data Shows
GERMANTOWN, Md., June 25, 2014 /PRNewswire/ -- Neuralstem, Inc. (NYSE MKT: CUR) announced that two sets of data from the NSI-189 clinical trial in major depressive disorder (MDD) were reported at two recent academic conferences: American Society of Clinical Psychopharmacology (ASCP) Annual Meeting, on June 17th, and the International College of Neuropyschopharmacology (CINP) Annual Meeting, on June 24th, 2014. NSI-189 is Neuralstem's lead proprietary neurogenic compound. At yesterday's CINP meeting, a poster presentation on quantitative EEG (qEEG) measurements, an electrophysical biomarker of depression, taken during the course of study showed that patients in the active treatment arm of the study:
- Had significantly increased brain wave patterns in the hippocampal region of the brain. Specifically, qEEG measurements at Day 28 showed statistical significance between the treatment and the placebo group in the electrical wave patterns emanating from specific areas of the brain, namely the left posterior temporal lobe and parietal region (p<0.02).
- Showed increased electrical coherence in the prefrontal cortical region, which is a pro-cognitive signal.
- Researchers concluded that these electrophysiological changes are consistent with the neurogenic hypothesis of the drug mechanism, which involves long-term structural changes in the hippocampus.
These results follow the 28-day clinical data presented at the ASCP meeting last week, which showed a significant and large treatment effect in the improvement of both depression and cognitive symptoms in the active therapy patients, compared to placebo, which continued eight weeks after treatment stopped, specifically:
- In a comprehensive assessment scale for depression (Symptoms of Depression Questionnaire or SDQ), the combined treatment group showed statistically significant improvement (p=0.02) after 28 days of the drug treatment compared to its randomized, double-blinded, placebo control group. There was a large effect size of 0.90.
- As measured by the assessment scale of cognitive and functioning deficits specifically designed for depressed patients (Cognitive and Physical Functioning Questionnaire or CPFQ), the treatment group was significantly better than the placebo group (p=0.01) at Day 28 with a large effect size of 0.94.
- As measured by both by SDQ and CPFQ, NSI-189's significant and large treatment effects continued for eight weeks even after the drug was withdrawn.
"This is a small study, but we should acknowledge the importance of showing such a powerful signal in such a small study in an indication with a very high placebo effect, historically," said Richard Garr, Neuralstem's President and CEO. "Additionally, we believe that no approved antidepressants have shown this type of long-term disease modifying property. If these large effect sizes and stable improvements in both depression and cognition are replicated with larger cohorts, we will pursue a breakthrough designation, with accelerated development prospects and reimbursement advantages. We plan to launch a large, multi-site Phase II study by the first quarter of 2015."
"We believe this qEEG data confirms that NSI-189 is affecting key circuitry common in both mood control and cognition, involving hippocampal neurogenesis and synaptogenesis," said Dr. Karl Johe, Neuralstem's Chairman and Chief Scientific Officer. "The next clinical trial will test two doses (40mg QD and 40mg BID), along with a randomized, double-blinded, placebo control group, in approximately 150 patients with confirmed diagnosis of recurrent MDD, with the aim of confirming these extremely promising results in a larger clinical setting."
About the Trial
In this single-site study, 24 patients with confirmed diagnosis of recurrent major depressive disorder (MDD), were treated orally with NSI-189 in three equal dose cohorts (8/dose cohort; 40mg QD, 40mg BID, and 40mg TID) for 28 days. Each dose cohort consisted of randomized, double-blinded, placebo controls at 1:3 ratio of placebo: drug. All subjects stayed in-clinic for the 28-day treatment period. After this period, the subjects returned to the clinic for follow-up measures for up to additional 8 weeks post dosing.
About Major Depressive Disorder
Major depressive disorder (MDD), also called major depression, is characterized by a combination of symptoms that interfere with a person's ability to function normally. MDD affects approximately 14.8 million American adults and is the leading cause of disability in the U.S. for ages 15-44, according to the National Institute of Mental Health. While most treatments modulate brain neurotransmitter levels to treat brain chemistry, new research suggests that brain physiology could also be involved. Depressed patients have reduced volume in the hippocampus, a part of the brain that generates new neurons. Neuralstem believes that stimulating the generation of new neurons in the hippocampus could potentially address the pathology of the depression itself.
Neuralstem's patented technology enables the production of neural stem cells of the brain and spinal cord in commercial quantities, and the ability to control the differentiation of these cells constitutively into mature, physiologically relevant human neurons and glial cells. Neuralstem's NSI-566 spinal cord-derived stem cell therapy is in Phase II clinical trials for amyotrophic lateral sclerosis (ALS), often referred to as Lou Gehrig's disease. Neuralstem has been awarded orphan status designation by the FDA for its ALS cell therapy.
In addition to ALS, the company is also targeting major central nervous system conditions with its NSI-566 cell therapy platform, including spinal cord injury and ischemic stroke. The company has received FDA approval to commence a Phase I safety trial in chronic spinal cord injury.
Neuralstem also maintains the ability to generate stable human neural stem cell lines suitable for systematic screening of large chemical libraries. Through this proprietary screening technology, Neuralstem has discovered and patented compounds that may stimulate the brain's capacity to generate neurons, possibly reversing pathologies associated with certain central nervous system conditions. The company has completed a Phase I safety trial evaluating NSI-189, its first neurogenic small molecule product candidate, for the treatment of major depressive disorder (MDD). Additional indications might include traumatic brain injury (TBI), Alzheimer's disease, and post-traumatic stress disorder (PTSD).
Cautionary Statement Regarding Forward Looking Information:
This news release may contain forward-looking statements made pursuant to the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Investors are cautioned that such forward-looking statements in this press release regarding potential applications of Neuralstem's technologies constitute forward-looking statements that involve risks and uncertainties, including, without limitation, risks inherent in the development and commercialization of potential products, uncertainty of clinical trial results or regulatory approvals or clearances, need for future capital, dependence upon collaborators and maintenance of our intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements. Additional information on potential factors that could affect our results and other risks and uncertainties are detailed from time to time in Neuralstem's periodic reports, including the annual report on Form 10-K for the year ended December 31, 2013 and Form 10Q, for the period ended March 31, 2014.
SOURCE Neuralstem, Inc.