Breakthrough Therapy Designation from U.S. Food and Drug Administration for Two Drugs for Patients with Major Depressive Disorder with Imminent Risk for Suicide
31 Aug 2018
Major depressive disorder (MDD) affects approximately 16 million people in the U.S. and 121 million people worldwide. As per the report on global burden of disease, the estimated point prevalence of unipolar depressive episodes is 1.9% and 3.2% among men and women, and the one-year prevalence at 5.8% and 9.5% for men and women, respectively. If the current trends for demographic and epidemiological transition continue, then by the year 2020, the burden of depression will increase to 5.7% of the total burden of disease, additionally it would also become the second leading cause of disability-adjusted life years (DALYs), second only to ischemic heart disease.
Depression leads an individual to experience continuous suffering from a serious, biologically based disease which can prevent them from enjoying life and functioning normally and is most commonly associated with suicide. There are more than 41,000 suicides each year in the U.S. alone, and most common reason for the same is untreated or poorly treated major depression. According to a study, people with depression die 7.9 years earlier than those without. While conventional antidepressants can be effective in treating major depressive disorder, and thereby suicidal ideation, they are not FDA-approved for this use, and their delayed onset of effect, which takes three to six weeks, limits their value in treating acutely suicidal patients. Depression, although being widely prevalent, is underserved and has seen scant innovation in decades. There remains a significant unmet need in treating MDD. Upwards of 70% of patients with MDD are partial or non-responders to first-line therapies, which include selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs).
Esketamine, developed by Johnson & Johnson and previously approved for treatment-resistant depression, in November 2013, is an N-methyl-D-aspartate (NMDA) receptor antagonist. It is an isomer of the generic anesthetic ketamine. It leads to an increased release of glutamate in synapses. Esketamine has shown remarkable results in patients with major depressive disorder with imminent risk for suicide in a Phase 2 clinical trial data, with some patients responding to treatment within hours. It has received a breakthrough therapy designation (BTD) from the FDA for MDD with imminent risk for suicide. It is delivered through intranasal route which offers fast-acting benefits, unlike standard oral treatment approaches. If approved by the FDA, esketamine would be one of the first new approaches to treat major depressive disorder available to patients in the last 50 years.
The common side effects observed during the Phase 2 study were dizziness, sedation, nausea, dissociation and perceptual changes, and small increases in pulse and blood pressure, however they were temporary and resolved within two hours. Janssen is currently working on Phase III plans for esketamine. The company is also conducting trials on esketamine in patients with treatment resistant depression. It received BTD for this indication in November 2013 and may file for marketing authorization in 2018.
Esketamine of Janssen is in a head-to-head race with rapastinel of Ireland-headquartered Allergan to lead the MDD market.
Rapastinel is an Allergan’s investigational drug, also known as GLYX-13. It received FDA BTD in February 2016. In the phase II trial conducted on rapastinel it was seen that rapastinel provides rapid antidepressant effect and was tolerable with no psychotomimetic or hallucinogenic side effects.