FDA Awards SPA Letter to NeuroRx for Pivotal Studies of NRX-101

The US Food and Drug Administration (FDA) today awarded a Special Protocol Agreement (SPA) letter to NeuroRx, a clinical-stage biopharmaceutical company, for NRX-101, the first drug regimen designed to treat patients with severe bipolar depression and acute suicidal ideation and behavior, the company announced.

The FDA has agreed to the design of a phase 2b/3 study of NRX-101, a formulation of d-cycloserine and lurasidone, with the primary endpoints being the change from baseline in measurements of depression via the Montgomery—Åsberg Depression Rating Scale (MADRS) and suicidality via the Columbia Suicide Severity Rating Scale (C-SSRS). Ultimately the goal is to enroll between 140 and 170 patients.

If successful, the therapy could have immense implications for patients suffering from depression with suicidal ideation, who face a multitude of treatment challenges.

“I think it’s becoming increasingly apparent that 50 years of serotonergic drugs have benefitted, at most, half of the people that need them,” Jonathan Javitt MD, MPH, the chief executive officer of NeuroRx, told MD Magazine at the American Psychiatric Association's annual meeting in New York City. “Every one of those drugs has a warning on the label that says it may cause suicide—and there’s a good reason for that. Everything you do to raise serotonin in the brain has the potential to cause an [adverse effect] called akathisia. People with bipolar depression, tragically, are even more susceptible.”

Although it only accounts for roughly 10% of all depression cases, bipolar depression accounts for up to 40% of suicides, Javitt noted. “Just a diagnosis of bipolar depression means that you have a 20% chance of dying from suicide at some point in your life,” he said.

Additionally, the company received a Letter of Support from the FDA’s Center for Drug Evaluation and Research encouraging its development of Glutamine+Glutamate (Glx) as a pharmacodynamic biomarker for depression. The letter was sent on the basis of both published and unpublished data that was reviewed by FDA and demonstrated a significant association between clinical symptoms of depression and levels of brain Glx, as measured by magnetic resonance spectroscopy.

“We have evidence that d-cycloserine and ketamine raise Glx in the brain,” Javitt said, “and an increase in Glx is directly associated with a decrease in depression. We think that this is the beginning of a whole new platform of antidepressant drugs. [This] is just the first generation.”

This effect from intravenous ketamine and oral d-cycloserine—both N-methyl-D-aspartate (NMDA) blocking drugs— is one that has not been observed in drugs targeting the serotonin pathway. Currently, none of the selective serotonin reuptake inhibitors (SSRIs), the most commonly prescribed medications for depression, have been shown to increase Glx.

NeuroRx also announced that its medical affairs department will meet with physicians interested in participating in upcoming clinical trials at the American Psychiatric Association’s annual meeting, in New York City. The company is located at Booth #1408.

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