Neuralstem, Inc. has announced the enrollment of its first patient in its double-blind, placebo-controlled multi-center Phase 2 study of a compound called NSI-189 for the treatment of MDD (major depressive disorder).
MDD usually consists of a persistent feeling of sadness or loss of interest. MDD can also include an inability to sleep or concentrate on tasks, changes in appetite, decreased energy level, and even thoughts of suicide.
MDD is treated with a variety of psychological therapies, such as
cognitive behavioral therapy, Behavior therapy, and Psychotherapy. Cognitive behavioral therapy is a type of talk therapy that focuses on changing a person’s thoughts in order to change their behavior and feelings. Behavior therapy focuses on changing behavior to help people break unhealthy habits. Psychotherapy treats mental or behavioral disorders through talk therapy. A medical procedure called electroconvulsive therapy is also used for some patients. Medications include antipsychotic medicines such as Aripiprazole (Abilify), anxiolytics like buspirone (Buspar), and antidepressants such as Trazodone (Oleptro), Bupropion (Wellbutrin), Duloxetine (Cymbalta) and a host of others.
The medications used to treat MDD regulate the levels of particular neurotransmitters (small molecules used neurons use to communicate with each other) in the brain.
NSI-189 works rather different from these other medications. NSI-189 activates neurogenesis, or the production of new neurons. The drug also activates the formation of new synapses and increases the volume of the hippocampus. All of these processes are thought to play a role in reversing depression. Such neurological outcomes can also enhance cognition and promote neuroregeneration.
This phase 2 trial will randomize 220 patients, in three cohorts, two of whom will receive the drug (40 mg twice a day or 40 mg once a day) and another of which will receive the placebo. Twelve different sites will participate in this MDD trial, all under the direction of Maurizio Fava.
The primary efficacy endpoint is a reduction in depression symptoms. The Montgomery-Asberg Depression Rating Scale (MADRS) will be used to assess thee severity of depression symptoms. Other endpoints will examine cognitive improvement measures.
The trial will last for 12 weeks, with an additional observational follow-up period of six months in order to assess NSI-189 long-lasting durability of benefits.
Neuralstem expects to report the results of this trial in the second half of 2017.
“A new class of treatment is needed in major depression, where existing compounds are not effective for all patients and have high side effect profile, so patients discontinue treatment,” said Fava. “We were encouraged by the signs of improvement in the depression and cognitive symptoms of MDD patients, as witnessed in Phase I with NSI-189, and look forward to validating in Phase 2.”
As mentioned in this statement to the press by Fava, NSI-189 successfully completed a phase I clinical trial for MDD in 2011. In this trial, NSI-189 was administered to 41 healthy volunteers. A phase Ib clinical trial for treating MDD in 24 patients was started in 2012 and completed in July 2014, and the results of this trial were published in December 2015.
NSI-189 works via a new pathway that is different from current antidepressants in that it appears to create long-lasting, positive structural changes in the brain.
In animal experiments, rodents treated with NSI-189 showed significant increases in synaptogenesis, neurogenesis, and hippocampal volume.
In the Phase 1b trial, therapeutic effects were observed in patients after completion of the 28-day dosing, and these improvements persisted for an additional 56 days without the drug. This seems to support the hypothesis of a new mechanism of action that induces long-lasting structural changes in key areas of the brain. In this trial, NSU-189 was shown to be safe and demonstrated large treatment effects in two key depression outcome measures.
The Phase 1b study also showed significant improvement in cognitive symptoms (as measured by the Cognitive and Physical Functioning Questionnaire), compared to placebo.
Brain imaging with quantitative EEGs showed an increase in alpha brain waves in two parts of the brain (left posterior temporal and left parietal region), both of which are involved in depression and cognition, compared to placebo.
No significant adverse effects were observed.
This new clinical trial will test the efficacy of this new drug to treat moderate to severe clinical depression.