Neuralstem has 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, and the International College of Neuropyschopharmacology (CINP) Annual Meeting. NSI-189 is Neuralstem’s lead proprietary neurogenic compound.
At the 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, 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 randomised, 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by SDQ and CPFQ, NSI-189’s significant and large treatment effects continued for eight weeks even after the drug was withdrawn.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,” says Richard Garr, Neuralstem’s president and chief executive officer. “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,” says 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 randomised, 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.”