The first new mechanism antidepressant in 30 years! Johnson Spravato nasal spray to submit new indications in the United States

October 10, 2019 / Biovalley BIOON/ - Johnson's Yang Sen pharmaceuticals recently announced that it has submitted a new drug application for Dutch act Spravato (esketamine) CIII nasal spray to the US Food and Drug Administration (FDA), seeking approval for a new indication of Spravato for severe depression with strong suicidal ideation (MDD) adult patients, rapid reduction of depressive symptoms If approved, spravato will be the first drug to be used in a population of patients with serious illness who are usually excluded from antidepressant treatment studies MDD patients with strong suicidal ideation constitute a mental emergency requiring immediate intervention Although antidepressants currently available are effective in many patients, they may take four to six weeks to work, providing only limited benefits to those with urgent needs Compared with the standard oral treatment drugs, spravato can provide the advantage of quick effect through intranasal administration This SNDA submission is based on the positive results of two key phase III clinical studies (aspire I & II) These two studies were double-blind, randomized, placebo-controlled, multicenter studies A total of 456 adult patients with moderate to severe MDD were enrolled More than 85% of them were assessed as moderate to extreme suicidal ideation by clinicians In the study, all patients received a comprehensive standard care plan (SOC), including first hospitalization and new / or optimized antidepressant treatment plan These patients were randomly assigned to receive spravato + SOC or placebo + SOC The main efficacy endpoint was the relief of depression 24 hours after the first administration, measured by the Montgomery - Spielberg Depression Rating Scale (MADRS) The secondary end point was the improvement in the severity of suicide measured by the revised cgi-ss-r 24 hours after the first administration It is worth mentioning that aspire I & II is one of the first global clinical studies to be conducted in a population of patients with this serious disease, who are usually excluded from antidepressant treatment studies The results of the two studies were presented at the 32nd annual meeting of the European Society for neuropsychopharmacology (ECNP) in Copenhagen, Denmark, on September 7 The results showed that when combined with comprehensive SOC, Spravato nasal spray treatment rapidly reduced the depressive symptoms in the high-risk group compared with placebo The results were as follows: 2 studies achieved their respective end point of treatment Compared with placebo +SOC treatment group, Spravato nasal spray 84mg+SOC treatment group had statistically significant advantage in reducing MDD depression symptoms (p=0.006) The data of reducing depressive symptoms were as follows: in two studies, MADRS was used 24 hours after the first administration, the average difference between the spravato + SOC treatment group and the placebo + SOC treatment group was 3.8 and 3.9 points respectively, in addition, 4 hours after the first administration, the spravato + SOC treatment showed significant effect on MDD symptoms From 4 hours to 25 days, both the spravato group and the placebo group continued to improve, and the degree of difference between the two groups remained largely unchanged throughout the 25 day double-blind period At the end of the double-blind period, 54% and 47% of the patients in the spravato treatment group were in remission (MADRS ≤ 12), respectively The clinical improvement of the two treatment groups in the double-blind period remained unchanged in the follow-up period of 9 weeks In terms of improvement of secondary end-point suicide severity: there was no significant difference in treatment between the two groups, which may be due to the substantial beneficial effect of comprehensive SOC used in clinical trials, including the dispersing effect of inpatient psychiatric treatment on acute suicide crisis in the two treatment groups In the two studies, spravato + SOC had good tolerance and no new safety signal The safety observed in the treatment of MDD patients with strong suicidal ideation in both studies was consistent with the previous clinical study evaluating spravato in the treatment of refractory depression (TRD) In the spravato + SOC group, the most common adverse reactions (> 10%) were dizziness, dissociation, nausea, drowsiness, blurred vision, vomiting, abnormal sensation, increased blood pressure and sedation, with the incidence more than twice that of the placebo + SOC group The active drug component of spravato is esketamine, which is a non competitive and subtype non selective activity-dependent N-methyl-D-aspartate (NMDA) receptor antagonist It has a new and unique mechanism of action Its principle of action is different from other drugs on the market for the treatment of depression NMDA receptor is a subtype of ionotropic glutamate receptor, which plays a key role in synaptic plasticity and information exchange between neurons In depression, blocking NMDA receptors is believed to improve brain plasticity and enhance synaptic connections In March this year, spravato was approved by the US FDA and became the first antidepressant drug with new mechanism in the past 30 years The drug is applicable to: combined with oral antidepressants, for the treatment of adult patients with refractory depression (TRD) Previously, FDA has awarded spravato a breakthrough drug qualification to treat TRD patients and MDD patients with imminent suicide risk Original source: Janssen submissions supplementary new drug application to U.S FDA for spravato? (esketamine) CIII nasal spray for the rapid reduction of