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30068311000001106

New Medicines

SpravatoMajor depressive disorder in adults judged clinically as a psychiatric emergency; acute short-term treatment

Information

Spravato
Licence extension / variation
Janssen
Janssen

Development and Regulatory status

Launched
Launched
Launched
February 2021
Feb 21Approved in EU and UK for the rapid reduction of depressive symptoms in a psychiatric emergency, for adult patients with a moderate-to-severe episode of major depressive disorder (MDD) [13].
Dec 20Recommended for EU approval by CHMP - the additional indication is, co-administered with oral antidepressant therapy, "in adults with a moderate to severe episode of Major Depressive Disorder, as acute short-term treatment, for the rapid reduction of depressive symptoms, which according to clinical judgement constitute a psychiatric emergency" [12].
Jul 20Licence change approved in US for use in combination with an oral antidepressant, to treat depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behaviour. The approval is based on two phase 3 clinical trials in which Spravato, plus comprehensive standard-of-care, demonstrated a significant and rapid reduction of depressive symptoms within 24 hours [11].
Jan 20Filed in the EU [10].
Oct 19Janssen submit sNDA to FDA for esketamine CIII nasal spray (Spravato) for rapid reduction of depressive symptoms in adults with major depressive disorder who have active suicidal ideation with intent [9].
Jan 19Company plans to file in the US for this indication; no details provided of EU plans [6].
Dec 17Johnson & Johnson has a second breakthrough therapy designation from the FDA for esketamine for the indication of major depressive disorder with imminent risk for suicide [3].
Jul 17PIII in EU & US [1].

Category

NMDA receptor antagonist; (S)-enatiomer of ketamine
An episode of depression serious enough to require treatment occurs in about 1 in 4 women and 1 in 10 men at some point in their lives. Some people have two or more episodes of depression at various times in their life. Prevalence of major depression in primary care is between 5% and 10%; two to three times as many people have depressive symptoms but do not meet criteria for major depression. Depression is the third most common reason for a consultation in primary care.
Major depressive disorder in adults judged clinically as a psychiatric emergency; acute short-term treatment
Intranasal

Further information

Yes

Trial or other data

Sep 19Positive results from PIII double-blind, randomised, placebo-controlled, multicentre trials, ASPIRE I and ASPIRE II (n=456), reported. Both studies met their respective primary efficacy endpoint, a reduction in depressive symptoms at 24 hours after the first dose, as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) with esketamine nasal spray 84 mg plus SOC showing superiority (p=0.006) vs placebo plus SOC. The studies also reported that both esketamine+SOC and placebo+SOC resulted in improvement in severity of suicidality as measured by the revised Clinical Global Impression of Severity of Suicidality (CGI-SS-R) at 24 hours after the first dose. The treatment difference between the two groups on this secondary endpoint was not statistically significant. The company suggest this may be due to the substantial beneficial effects of comprehensive SOC used in the trial. Esketamine nasal spray was well-tolerated with no new safety signals. In the esketamin+SOC group, the most common adverse events (≥10%), with a frequency of more than twice that of the placebo+SOC group, were dizziness, dissociation, nausea, somnolence, vision blurred, vomiting, paresthesia, increased blood pressure and sedation [8].
Jun 19PIII Aspire II study (NCT03097133) has finished recruiting and collecting primary outcome data [7].
Nov 18PIII Aspire II study (NCT03097133) is still recruiting; collection of primary outcome data now expected to complete Jul 19 [5].
Apr 18Positive data from 12-week, PIIa, randomised, double-blind, placebo-controlled, multicentre study in 68 adults with major depressive disorder who were assessed to be at imminent risk for suicide. Pts were randomised 1:1 to receive standard of care (SOC) plus esketamine nasal spray 84 mg (N=36) or placebo nasal spray (N=32) for 25 days. The primary efficacy endpoint was achieved, with the mean change from baseline at 4 hours post-dose showing a rapid, clinically meaningful and statistically significant improvement in depressive symptoms of -13.4 (9.03) for esketamine nasal spray 84 mg plus SOC, compared to -9.1 (8.38) for placebo nasal spray plus SOC, p=0.015; p=0.61. Esketamine nasal spray was generally well-tolerated based on the adverse event data from this study. The most common (>20%) treatment-emergent adverse events (TEAEs) in the esketamine nasal spray group during the double-blind phase were: nausea (37.1%), dizziness (34.3%), unpleasant taste (31.4%), dissociation (31.4%), headache (31.4%), and vomiting (20.0%).[4]
Sep 17PIII trial to evaluate the efficacy and safety of intranasal esketamine in addition to comprehensive standard of care for the rapid reduction of the symptoms of MDD, including suicidal ideation, in adult patients assessed to be at imminent risk for suicide starts (Aspire II; NCT03097133). Change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) total score at 24 hours post first dose will be the primary endpoint. It will enrol approximately 224 patients in the US, Argentina, Austria, Belgium, Brazil, Canada, Czech Republic, France, Lithuania, Poland, Turkey and the UK. Collection of primary outcome data is expected to complete Sep 19 [2].

Evidence based evaluations

KeyzilenAcute inner ear tinnitus - first-line up to 3 months from onset

Information

Keyzilen
New formulation - repurposed medicine
Altamira therapeutics
Altamira therapeutics

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials
Nov 21: No further development reported. Further PII/PIII trial planned [15]

Category

NMDA receptor antagonists. Biocompatible gel formation of a cochlear N-methyl-D-aspartate (NMDA) receptor antagonist.
As many as 1 in 10 people have persistent tinnitus that is mild and not very troublesome. However, about 1 in 100 people have tinnitus which persists most of the time, and severely affects their quality of life [2].
Acute inner ear tinnitus - first-line up to 3 months from onset
Intratympanic

Trial or other data

Sep 19Auris announced they have met with the EMA and FDA and obtained advice on the development plan and regulatory pathway for esketamine (Keyzilen), and plans for a further PII/III trial with funding options under consideration [13]
Mar 18The company announced that the TACTT3 trial failed to meet its primary efficacy endpoint of a statistically significant improvement in the Tinnitus Functional Score from baseline to Day 84 in the active treated group compared to placebo either in the overall population or in the otitis media subpopulation [11]