NeuroRx has signed a Cooperative Research and Development Agreement (CRADA) with the U. S. Department of Veterans Affairs, as represented by the Michael E. DeBakey VA Medical Center in Houston, TX and the Houston VA Research & Education Foundation. The collaboration also includes Baylor College of Medicine, in Houston, TX. NeuroRx is developing a sequential treatment regimen of NRX-100 (ketamine) and NRX-101 (a proprietary formulation of d-cycloserine / lurasidone), for the treatment of severe bipolar depression in patients with Acute Suicidal Ideation & Behavior (ASIB). The FDA awarded FAST TRACK designation to this investigational drug regimen in September, 2017. NeuroRx has now signed agreements with three clinical trial centers, including one with the University of Alabama, Birmingham. Patient enrollment will begin shortly. The company is in active discussions with additional sites with which it expects to form contracts in early 2018.
There currently is no approved drug therapy for bipolar depression in patients with Acute Suicidal Ideation and Behavior (ASIB); the only FDA-approved treatment is electroconvulsive therapy (ECT). In fact, most antidepressants carry a warning about their potential for increasing the risk of suicide.
"A relatively high proportion of individuals with bipolar disorder attempt suicide in their lifetime, yet patients with Acute Suicidal Ideation and Behaviors have been excluded from virtually all clinical studies," said Sanjay J. Mathew, M.D., Professor in the Menninger Department of Psychiatry and Behavioral Sciences at Baylor College of Medicine. "There is a tremendous unmet need to develop rapid-acting and life-saving new interventions for these individuals, including many veterans and active-duty military personnel. This groundbreaking clinical trial is of critical importance to our field."
Bipolar disorder, which affects 5.7 million Americans, is characterized by significant changes in mood, from mania or hypomania, to depression, often quite severe. The depressive phase, which is called "bipolar depression," can trigger suicidal thoughts and behaviors. Standard-of-care consists of hospitalized observation and electroconvulsive therapy (ECT). Unfortunately, most commonly-used antidepressants bear an FDA-mandated warning label identifying their potential to increase the risk of suicide.
Each day, approximately 100 Americans, and more than 2,100 people worldwide, end their lives by suicide, according to American Foundation for Suicide Prevention (AFSP) and the World Health Organization (WHO). Although only 10% of all people with depression have bipolar depression, NeuroRx estimates that bipolar depression accounts for nearly half of all suicides each year. Estimates indicate that 50% or more of individuals with bipolar disorder attempt suicide and that 11% or more succumb to suicide.
NRX-101 is a patented, oral, fixed-dose combination of two FDA-approved drugs: d-cycloserine, a N-methyl-D-aspartate (NMDA) receptor modulator, and lurasidone, a 5-HT2a receptor antagonist. NeuroRx's investigational treatment approach begins with a single dose of NRX-100 (ketamine), an FDA-approved anesthetic, for initial stabilization, followed by approximately six weeks of daily oral NRX-101.
Results from two Phase II clinical studies, involving 26 and 8 patients respectively, have been published in peer-reviewed journals. The first study showed a 50% reduction in symptoms of depression in patients with major depressive disorder, and the second, a 75% reduction in suicidal ideation in bipolar patients. In both studies patients were on background antidepressant therapy and then treated with d‑cycloserine, one of the active ingredients in NRX-101.