The first new mechanism antidepressant in 30 years! Johnson Spravato nasal spray, US Europe to apply for new indications, treat patients with urgent Dutch act ideation.

2020 01 / 17 / X Bio Valley BIOON/ - Johnson's Yang Sen pharmaceuticals recently announced that it has submitted a new II application for Spravato (esketamine) nasal spray to the European Medicines Agency (EMA) The application aims to expand the use of spravato beyond its current indications As an acute short-term treatment drug, it is used in combination with oral antidepressants for adult patients with moderate to severe depressive episodes and suicidal ideation of major depression (MDD) to rapidly reduce 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 In the United States, Janssen Pharmaceutical submitted a new drug supplement application (SNDA) to the FDA in October 2019, seeking approval of spravato for the same indications Spravato is the first antidepressant drug with new mechanism approved in more than 30 years In the United States and the European Union, spravato was approved in March and December 2019, respectively, to treat adult patients with refractory depression (TRD) in combination with oral antidepressants MDD patients assessed as having an imminent risk of suicide constitute a mental emergency requiring immediate intervention Although currently available antidepressants are effective in the treatment of depression, they usually take weeks (4-6 weeks) to achieve full effect This delay has potential risks, especially since the risk of suicide is highest early in the treatment Compared with the standard oral treatment drugs, spravato can provide the advantage of quick effect through intranasal administration This type II change request 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 of Neuropsychopharmacology (ECNP) in Copenhagen, Denmark, in September 2019 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 Globally, major depression (MDD) is the leading cause of disability, which can affect people of different ages Patients with depression (including MDD) continue to suffer from severe disease, which has a significant negative impact on physical function and all aspects of life Although the antidepressants currently available are effective in many patients, the onset time is 4 to 6 weeks, and about one third of patients have no response to the currently available treatment 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 the United States, spravato was approved in March 2019 for use in combination with oral antidepressants in adults with refractory depression (TRD) Previously, FDA has awarded spravato a breakthrough drug qualification to treat TRD patients and MDD patients with imminent suicide risk In the European Union, spravato was approved in December 2019 for the combination of a selective serotonin reuptake inhibitor (SSRI) or a serotonin and noradrenaline reuptake inhibitor (SNRI) for the treatment of adult patients with TRD Patients with depression are considered to have TRD if they do not respond to at least two different antidepressants in their current moderate to severe depressive episode, according to approval This EC approval is valid in 28 EU Member States and European Economic Area (EEA) countries (Norway, Iceland, Liechtenstein) Source of original text: Janssen seeks expanded use of spravato? () nasal spray in Europe as a treatment for expressive symptoms in results with major expressive discorder who have current satisfactory idea with intent