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The first new mechanism antidepressant in 30 years! Johnson & Johnson Spravato Nasal Spray Submits New Indication Application in the U.S.
Author : admin Time : 2019/12/5 21:15:38Click :
October 10, 2019 / Bio Valley BIOON /-Janssen Pharmaceuticals, a Johnson & Johnson subsidiary, recently announced that it has submitted a new supplement to the US Food and Drug Administration (FDA) depression drug Spravato (esketamine) CIII nasal spray The application (sNDA) seeks approval for a new indication for Spravato for adult patients with severe depression (MDD) who have a strong suicidal ideation to rapidly reduce depressive symptoms. If approved, Spravato will be the first drug to be used in a group of patients with severe illnesses that are normally excluded from antidepressant treatment research.
MDD patients with strong suicidal thoughts constitute a type of mental emergency that requires immediate intervention. Although currently available antidepressants are effective for many patients, their onset of action may take 4 to 6 weeks and only provide limited benefits to those patients with urgent needs. Compared to standard oral therapies, Spravato offers the advantage of rapid onset of administration by intranasal route.
The submission of the sNDA is based on the positive results of two key Phase III clinical studies (ASPIRE I & II). Both studies were double-blind, randomized, placebo-controlled, and multicenter studies. A total of 456 adults with moderate to severe MDD were enrolled, and more than 85% of them were rated by clinicians as moderate to extreme suicidal ideation. In the study, all patients received a comprehensive standard care regimen (SOC), including a first hospital stay and a newly started / or optimized antidepressant treatment regimen. These patients were randomly assigned to receive either Spravato + SOC or placebo + SOC. The primary efficacy endpoint was a reduction in depressive symptoms 24 hours after the first dose, measured using the Montgomery-Sberg Depression Rating Scale (MADRS). The secondary endpoint was to use the revised Suicide Severity Clinical Overall Impression Scale (CGI-SS-R) to measure improvements in suicide severity 24 hours after the first dose.
It is worth mentioning that ASPIRE I & II is the first global clinical study conducted in this group of patients with severe diseases, and such patients are usually excluded from antidepressant treatment research. The results of the two studies were presented at the 32nd European Neuropsychopharmacological Society's Annual Conference (ECNP) 2019 in Copenhagen, Denmark, on September 7. The results showed that when combined with comprehensive SOC, Spravato nasal spray therapy rapidly reduced depression symptoms in this high-risk patient population compared to placebo.
The specific results were: Both studies reached their respective primary efficacy endpoints-compared with the placebo + SOC treatment group, the Spravato intranasal spray 84mg + SOC treatment group had a statistically significant advantage in rapidly reducing MDD depression symptoms (P = 0.006).
Data on the reduction of depressive symptoms were: In two studies, MADRS measurements were performed 24 hours after the first dose. The average difference between the Spravato + SOC treatment group and the placebo + SOC treatment group was 3.8 and 3.9 points, respectively. Four hours after the administration, Spravato + SOC treatment showed a significant effect on MDD symptoms. From 4 hours to 25 days, both the Spravato-treated and placebo groups 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 patients in the Spravato treatment group had remissions (MADRS score ≤ 12 points) in the two studies. The clinical improvement of the two treatment groups in the double-blind period remained unchanged during the follow-up period of 9 weeks.
Improvement in the suicidal severity of the secondary endpoint: There was no statistically significant difference in treatment between the two groups, which may be due to the substantial beneficial effects of the comprehensive SOC used in clinical trials, including hospitalization of patients with mental illness for patients in the two treatment groups The decentralized effect of the acute suicide crisis.
In two studies, the Spravato + SOC protocol was well tolerated and there were no new safety signals. The safety observed in treating MDD with strong suicidal thoughts in both studies was consistent with previous clinical studies evaluating Spravato for refractory depression (TRD). In the Spravato + SOC group, the most common adverse reactions (> 10%) were dizziness, dissociation, nausea, drowsiness, blurred vision, vomiting, paresthesia, increased blood pressure, and sedation. 2 times more.
Spravato's active pharmaceutical ingredient is esketamine, a non-competitive and subtype non-selective activity-dependent N-methyl-D aspartate (NMDA) receptor antagonist with a new and unique mechanism of action Its principle of action is different from other depression treatment drugs currently on the market. The NMDA receptor is a subtype of the ionic glutamate receptor and plays a key role in synaptic plasticity and information exchange between neurons. In depression, blocking NMDA receptors is thought to improve brain plasticity and enhance synaptic connections.
In March of this year, Spravato was approved by the US FDA, becoming the first antidepressant with a new mechanism of action in the past 30 years. The drug is suitable for: combined oral antidepressants for the treatment of adult patients with refractory depression (TRD) treatment. Previously, the FDA has granted Spravato breakthrough drug eligibility for TRD patients and MDD patients with an immediate risk of suicide.
MDD patients with strong suicidal thoughts constitute a type of mental emergency that requires immediate intervention. Although currently available antidepressants are effective for many patients, their onset of action may take 4 to 6 weeks and only provide limited benefits to those patients with urgent needs. Compared to standard oral therapies, Spravato offers the advantage of rapid onset of administration by intranasal route.
The submission of the sNDA is based on the positive results of two key Phase III clinical studies (ASPIRE I & II). Both studies were double-blind, randomized, placebo-controlled, and multicenter studies. A total of 456 adults with moderate to severe MDD were enrolled, and more than 85% of them were rated by clinicians as moderate to extreme suicidal ideation. In the study, all patients received a comprehensive standard care regimen (SOC), including a first hospital stay and a newly started / or optimized antidepressant treatment regimen. These patients were randomly assigned to receive either Spravato + SOC or placebo + SOC. The primary efficacy endpoint was a reduction in depressive symptoms 24 hours after the first dose, measured using the Montgomery-Sberg Depression Rating Scale (MADRS). The secondary endpoint was to use the revised Suicide Severity Clinical Overall Impression Scale (CGI-SS-R) to measure improvements in suicide severity 24 hours after the first dose.
It is worth mentioning that ASPIRE I & II is the first global clinical study conducted in this group of patients with severe diseases, and such patients are usually excluded from antidepressant treatment research. The results of the two studies were presented at the 32nd European Neuropsychopharmacological Society's Annual Conference (ECNP) 2019 in Copenhagen, Denmark, on September 7. The results showed that when combined with comprehensive SOC, Spravato nasal spray therapy rapidly reduced depression symptoms in this high-risk patient population compared to placebo.
The specific results were: Both studies reached their respective primary efficacy endpoints-compared with the placebo + SOC treatment group, the Spravato intranasal spray 84mg + SOC treatment group had a statistically significant advantage in rapidly reducing MDD depression symptoms (P = 0.006).
Data on the reduction of depressive symptoms were: In two studies, MADRS measurements were performed 24 hours after the first dose. The average difference between the Spravato + SOC treatment group and the placebo + SOC treatment group was 3.8 and 3.9 points, respectively. Four hours after the administration, Spravato + SOC treatment showed a significant effect on MDD symptoms. From 4 hours to 25 days, both the Spravato-treated and placebo groups 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 patients in the Spravato treatment group had remissions (MADRS score ≤ 12 points) in the two studies. The clinical improvement of the two treatment groups in the double-blind period remained unchanged during the follow-up period of 9 weeks.
Improvement in the suicidal severity of the secondary endpoint: There was no statistically significant difference in treatment between the two groups, which may be due to the substantial beneficial effects of the comprehensive SOC used in clinical trials, including hospitalization of patients with mental illness for patients in the two treatment groups The decentralized effect of the acute suicide crisis.
In two studies, the Spravato + SOC protocol was well tolerated and there were no new safety signals. The safety observed in treating MDD with strong suicidal thoughts in both studies was consistent with previous clinical studies evaluating Spravato for refractory depression (TRD). In the Spravato + SOC group, the most common adverse reactions (> 10%) were dizziness, dissociation, nausea, drowsiness, blurred vision, vomiting, paresthesia, increased blood pressure, and sedation. 2 times more.
Spravato's active pharmaceutical ingredient is esketamine, a non-competitive and subtype non-selective activity-dependent N-methyl-D aspartate (NMDA) receptor antagonist with a new and unique mechanism of action Its principle of action is different from other depression treatment drugs currently on the market. The NMDA receptor is a subtype of the ionic glutamate receptor and plays a key role in synaptic plasticity and information exchange between neurons. In depression, blocking NMDA receptors is thought to improve brain plasticity and enhance synaptic connections.
In March of this year, Spravato was approved by the US FDA, becoming the first antidepressant with a new mechanism of action in the past 30 years. The drug is suitable for: combined oral antidepressants for the treatment of adult patients with refractory depression (TRD) treatment. Previously, the FDA has granted Spravato breakthrough drug eligibility for TRD patients and MDD patients with an immediate risk of suicide.
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