NeuroRx Announces FDA Breakthrough Therapy Designation for NRX-101, First Oral Rapid-Acting Antidepressant for Suicidal Bipolar Depression

VCBeat (WeChat ID: vcbeat) has learned that on November 13, 2018 (U.S. local time), NeuroRx, a clinical-stage pharmaceutical company, announced that its investigational drug NRX-101 had been granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration (FDA). The drug is primarily indicated for the treatment of patients with severe bipolar depression experiencing acute suicidal ideation and behavior (ASIB), making it the first oral rapid-acting antidepressant to receive Breakthrough Therapy Designation. Earlier this April, the FDA issued a Special Protocol Assessment (SPA) for the company’s ongoing pivotal Phase 2b/3 clinical trial. In a recent report, NeuroRx disclosed encouraging results from its STABIL-B study, which demonstrated that NRX-101 was well tolerated, with no serious adverse events or discontinuation due to side effects.

NRX-101 is an oral combination therapy comprising fixed doses of D-cycloserine (DCS), an NMDA antagonist, and lurasidone, which exhibits 5-HT2A receptor antagonist activity. Unlike all previously approved antidepressants, DCS elevates the levels of two neurotransmitters: glutamate and glutamine (Glx). Consequently, NRX-101 may represent a novel class of antidepressants with the potential to genuinely reduce suicidal ideation in patients with severe bipolar depression. In contrast, prior serotonergic antidepressants have been associated with an increased risk of suicidality in certain vulnerable populations.

Image source: NeuroRx official website

The key reason NRX-101 is poised to become the first oral, rapid-acting antidepressant to receive FDA Breakthrough Therapy Designation lies in the clinical data obtained from the multicenter STABIL-B feasibility study, which was designed to evaluate the clinical efficacy of NRX-101 compared with a lurasidone control group. These data will be presented next month at the annual meeting of the American College of Neuropsychopharmacology.

Jonathan Javitt, CEO of NeuroRx, stated, “The FDA’s granting of Breakthrough Therapy Designation to NRX-101 recognizes the unique unmet medical needs faced by patients with severe bipolar depression. These patients have historically been nearly excluded from clinical trials for all antidepressant medications currently on the market. We are eager to change this reality, as more than 150,000 Americans receive emergency care each year, and over 25,000 die annually from this fatal illness.”

Bipolar depression, also known as bipolar disorder, currently affects approximately 5.7 million patients in the United States. It is characterized by significant mood fluctuations, with patients experiencing a progression from mania to hypomania, and ultimately to depression. The suicide rate among patients with bipolar depression is substantially higher than that among patients with major depressive disorder. Data indicate that up to 20% of individuals with bipolar depression die by suicide, while more than 50% have attempted suicide. Previously, the only FDA-approved treatment for suicidal bipolar depression was electroconvulsive therapy (ECT), which increases levels of Glx (glutamate and glutamine) in the brain. Although ECT can effectively reduce the risk of suicide, it is associated with numerous well-known side effects, including confusion and memory loss. Meanwhile, most commonly used antidepressant medications on the market carry FDA-mandated warning labels identifying the potential for increased suicide risk.

NeuroRx is currently conducting a pivotal Phase 2b/3 clinical trial under a Special Protocol Assessment (SPA), evaluating daily oral NRX-101 versus standard of care (lurasidone) in patients with severe bipolar depression and acute suicidal ideation following initial stabilization with ketamine. Previously, NeuroRx was granted Fast Track designation by the FDA in August 2017.

Breakthrough Therapy Designation was established in 2012 under the U.S. FDA’s Food and Drug Administration Safety and Innovation Act (FDASIA), aiming to accelerate the development and review of drugs and biologics intended to treat serious or life-threatening conditions. Preliminary clinical evidence indicates that drugs and biologics granted Breakthrough Therapy Designation can significantly improve clinical outcomes compared with existing therapies. From the program’s inception through 2017, only 46 drugs received this designation, 38 of which were used to treat cancer, infectious diseases, and metabolic disorders. Breakthrough Therapy Designation reflects the FDA’s commitment to efficient drug development and provides enhanced guidance; compared with other FDA priority programs or drugs without priority designation, it substantially reduces average development time.

NeuroRx, founded in 2015 and headquartered in Wilmington, Delaware, is a clinical-stage biopharmaceutical company. The company is advancing the clinical development of its lead candidate, NRX-101, the world’s first oral therapy for acute suicidal ideation and behavior (ASIB) in bipolar depression. Previously, NeuroRx secured $6.7 million in financing in 2016.