SPRAVATO® (esketamine nasal spray) authorised in Europe
Posted in Industry News on 11th Feb 2021
SPRAVATO® (Esketamine Nasal Spray) Authorised in Europe for the Rapid Reduction of Depressive Symptoms in a Psychiatric Emergency for Adult Patients with a Moderate to Severe Episode of Major Depressive Disorder
- This makes esketamine nasal spray the first N-methyl-D-aspartate (NMDA) antagonist to be authorised for adult patients with a moderate to severe episode of major depressive disorder (MDD) in a psychiatric emergency1–3
- European Commission (EC) authorisation is based on results from two Phase 3 ASPIRE studies, which evaluated the efficacy and safety of esketamine nasal spray used in addition to comprehensive standard of care (SOC)4–6
- This authorisation marks the second indication for esketamine nasal spray in the European Economic Area (EEA), Northern Ireland and Great Britain7
The Janssen Pharmaceutical Companies of Johnson & Johnson has announced that the European Commission (EC) has authorised the expanded use of SPRAVATO® (esketamine nasal spray), co-administered with oral antidepressant therapy in adults with a moderate to severe episode of major depressive disorder (MDD), as acute short-term treatment, for the rapid reduction of depressive symptoms, which according to clinical judgement constitute a psychiatric emergency.7
The EC authorisation of esketamine nasal spray was based on data from the Phase 3, short-term (four weeks), double-blind, randomised, placebo controlled, multicentre, ASPIRE I & II clinical studies conducted globally. These studies compared the efficacy and safety of esketamine nasal spray in combination with comprehensive standard of care (SOC) against placebo nasal spray in combination with comprehensive SOC in adult patients with moderate to severe MDD and current/active suicidal ideation with intent. The comprehensive SOC included initial psychiatric hospitalisation and newly initiated or optimised oral antidepressant (AD) therapy (AD monotherapy or AD plus augmentation [e.g., second antidepressant, an atypical antipsychotic, or a mood stabilizer]), which was determined by the treating physician based on clinical judgement and practice guidelines, for the duration of the studies. The comprehensive SOC was enhanced by twice-weekly visits with extensive clinical contact, and concomitant use of benzodiazepines was permitted during the study.4,5 Psychotherapy was also permitted during the ASPIRE II trial.5
In each study, the primary efficacy measure was the reduction of symptoms of MDD as measured by the change from baseline Montgomery-Åsberg Depression Rating Scale (MADRS)* total score at 24 hours after first dose.7 Patients treated with esketamine nasal spray accompanied by comprehensive SOC achieved a difference of -3.8 (pooled) in depressive symptoms (reduction from baseline MADRS total score) at 24 hours after receiving the first dose compared to placebo nasal spray in combination with comprehensive SOC, which is a statistically significant (p=0.006 in each of the two studies) and clinically meaningful reduction.4,5,7,8 The benefit of esketamine nasal spray plus comprehensive SOC on symptoms of MDD was apparent as early as four hours after the first dose.4,5 The effectiveness of esketamine nasal spray in preventing suicide or in reducing suicidal ideation or behaviour was not demonstrated.
The safety profile for esketamine nasal spray in this patient population was consistent with previous studies in adults with treatment-resistant major depressive disorder (TRD).1,9 The most common treatment-emergent adverse events (≥20 per cent) observed in the esketamine nasal spray plus comprehensive SOC group versus the placebo nasal spray plus comprehensive SOC group in the ASPIRE 1 trial were dizziness (35.4 per cent vs 8.9 per cent), dissociation (29.2 per cent vs 3.6 per cent), and nausea (20.4 per cent vs 13.4 per cent). In the ASPIRE 2 trial they were dizziness (41.2 per cent vs 18.6 per cent), dissociation (38.6 per cent vs 8.0 per cent), nausea (33.3 per cent vs 14.2 per cent), as well as dysgeusia (25.4 per cent vs 15.9 per cent), somnolence (22.8 per cent vs 10.6 per cent), headache (20.3 per cent vs 20.4 per cent), and paraesthesia (20.2 per cent vs 6.2 per cent) respectively.4,5
This authorisation of esketamine nasal spray by the European Commission is a welcome and significant step toward reducing the burden faced by many adults with major depressive disorder in Europe, and is part of Janssen’s commitment to patients with serious mental illnesses. This new indication for esketamine nasal spray provides psychiatrists with an innovative treatment option to help their adult patients needing urgent relief from debilitating symptoms during a psychiatric emergency based on clinical judgment.
Tito Roccia, Therapeutic Area Medical Affairs Director, Neuroscience, Janssen-Cilag Ltd.
This EC authorisation is valid in all 27 member states of the European Union as well as the EEA countries (Norway, Iceland, and Liechtenstein), Northern Ireland, and may be implemented in relation to the converted EU Marketing Authorisation in Great Britain.
Esketamine nasal spray is already authorised by the EC for use in combination with a selective serotonin reuptake inhibitor (SSRI) or serotonin and norepinephrine reuptake inhibitor (SNRI), for adults with treatment-resistant Major Depressive Disorder (TRD), who have not responded to at least two different treatments with antidepressants in the current moderate to severe depressive episode.7
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- Canuso C, et al. Presented at 58th Annual Meeting of Neuropsychopharmacology (ACNP); December 2019.
- Summary of Product Characteristics. Spravato 28 mg nasal spray. Janssen-Cilag International. Last updated February 2021.
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- Johnson & Johnson Ltd. Press release on December 2019. Available at: https://www.janssen.com/emea/sites/www_janssen_com_emea/files/spravatorv_esketamine_nasal_spray_approved_in_europe_for_adults_with_treatment-resistant_major_depressive_disorder.pdf (last accessed February 2021).
- Johnson & Johnson Ltd. Press release on March 2019. Available at: https://www.jnj.com/janssen-announces-u-s-fda-approval-of-spravatotm-esketamine-ciii-nasal-spray-for-adults-with-treatment-resistant-depression-trd-who-have-cycled-through-multiple-treatments-without-relief (last accessed February 2021).
- Johnson & Johnson Ltd. Press release on August 2020. Available at: https://www.jnj.com/janssen-announces-u-s-fda-approval-of-spravato-esketamine-ciii-nasal-spray-to-treat-depressive-symptoms-in-adults-with-major-depressive-disorder-with-acute-suicidal-ideation-or-behavior (last accessed February 2021).
- World Health Organization (WHO). Depression and Other Common Mental Health Disorders: Global Health Estimates, 2017. Available at: http://www.who.int/mental_health/management/depression/prevalence_global_health_estimates/en/ (last accessed February 2021).
- World Health Organization (WHO). Depression. Available at: http://www.who.int/news-room/fact-sheets/detail/depression (last accessed February 2021).
- World Health Organization (WHO). International Classification of Diseases 11th Revision (ICD-11). 6A71.3. 2019. Available at: https://icd.who.int/browse11/l-m/en#/http%3a%2f%2fid.who.int%2ficd%2fentity%2f2139612744 (last accessed February 2021).
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- Ionescu D, et al. Dialogues Clin Neurosci 2015;17(2):111–126.