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Preliminary findings show safety, tolerability of NSI-189 for MDD
Results from a randomized, double-blind, placebo-controlled study showed safety and tolerability of a small molecule drug, NSI-189, among adults with major depressive disorder.
“This small phase 1B trial achieved the primary goal of establishing safety and tolerability of NSI-189 at multiple doses. However, in addition, it is also encouraging to see the early signs of benefit this novel treatment may offer for patients living with [major depressive disorder (MDD)],” Maurizio Fava, MD, of Massachusetts General Hospital, Clinical Trials and Network Institute, Boston, said in a press release. “Improvements in depression and cognitive symptoms, if confirmed in future studies, indicate the promise NSI-189 holds for the treatment of MDD.”
Researchers evaluated tolerability of 40 mg of NSI-189 (Neuralstem) administered once, twice or three times daily for 28 days among 24 adults with MDD. After 28 days, participants were discharged and assessed in periodic follow-ups for 8 weeks. Safety, pharmacokinetic, pharmacodynamic and clinical assessments were conducted throughout the 84-day study.
Across all three doses, NSI-189 was well-tolerated with no serious adverse events.
The mean half-life of the drug was 17.4 to 20.5 hours, with steady-state reached after 96 to 120 hours.
NSI-189 significantly improved Symptoms of Depression Questionnaire (SDQ) and Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) scores, and had a medium-to-large effect size across all other depressive and cognitive measures, including the Montgomery-Asberg Depression Scale (MADRS) and the Clinical Global Impressions-Improvement.
These improvements continued during the 8-week, drug-free phase, according to the release.
Based on MADRS scores, 12 of the 18 participants who completed the study were responders, with a 50% decrease in MADRS scores or return to a normal range. Two participants were nonresponders and four were considered partial responders with posttreatment MADRS scores that indicated a change from moderate to mild depression.
Further, MRI analysis showed a modest increase in left hippocampal volume among participants who received NSI-189, though it was not statistically significant.
Volume increase trends in the amygdala over time were not significant on the left side but were significant on the right side of the brain.
“These results are promising, as it is unusual to see medium-to-large clinical effects from such a small study, particularly in the case of depression where placebo effects can be quite large,” Karl Johe, PhD, chairman and chief scientific officer of Neuralstem, said in the release. “Similar results were seen across several outcome measures and corroborated by blood biomarkers and brain activity and volume. This suggests that the neurogenic mechanism of action of NSI-189 is targeting the core of depression disease. If replicated in the upcoming phase 2 trial, NSI-189 may have potential as a disease modifying agent as indicated by positive effects continued after patients stopped receiving the drug.”
As a result of the study findings, Neuralstem has filed a phase 2 efficacy study of NSI-189 for treatment of MDD as a monotherapy with the FDA. – by Amanda Oldt
Disclosure: Fava reports no relevant financial disclosures. Please see the full study for a list of all authors’ relevant financial disclosures.