SCOTTISH MEDICINES CONSORTIUM (SMC) ACCEPTS SPRAVATO®▼ (ESKETAMINE) NASAL SPRAY FOR USE IN TREATMENT OF ADULTS WITH TREATMENT-RESISTANT MAJOR DEPRESSIVE DISORDER IN SCOTLAND

SCOTTISH MEDICINES CONSORTIUM (SMC) ACCEPTS SPRAVATO^®▼ (ESKETAMINE) NASAL SPRAY FOR USE IN TREATMENT OF ADULTS WITH TREATMENT-RESISTANT MAJOR DEPRESSIVE DISORDER IN SCOTLAND

 

SPRAVATO^® (esketamine) nasal spray is the first antidepressant with a new mechanism of action in 30 years to treat major depressive disorder (MDD)

 

High Wycombe, UK, 7^th September 2020 – The Janssen Pharmaceutical Companies of Johnson & Johnson welcomes the Scottish Medicines Consortium’s (SMC) decision to accept SPRAVATO^® (esketamine) nasal spray for use within NHS Scotland in combination with a selective serotonin reuptake inhibitor (SSRI) or serotonin-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.[i]

 

Major depressive disorder (MDD) is a significant health condition that has a profound impact on people’s lives. Up to 30 per cent of people living with MDD are considered to have TRD, which can cause significantly lower health-related quality of life, reduced productivity at work and increased absenteeism.^{[ii][iii],-[iv],—}[v] People living with MDD can suffer with depressive episodes for many months or even years before being diagnosed and the effects go beyond the psychiatric and physical symptoms, affecting employment and education, relationships, health and overall quality of life.^[vi],[vii]

“Janssen is pleased with the SMC’s swift decision to accept the use of esketamine nasal spray in eligible patients, and we applaud the SMC’s pragmatic approach and flexibility in reaching this positive recommendation,” commented Amanda Cunnington, Director of Health Economics, Market Access, Reimbursement (HEMAR) & Patient Engagement and Government Affairs, Janssen-Cilag Limited. “We recognise this outcome results in a discrepancy in access between patients in Scotland and those in the rest of the UK and are currently working closely with NICE in the hope that patients will also be able to access esketamine nasal spray routinely in England, Wales and Northern Ireland.”

 

Esketamine is a glutamate receptor modulator which works on the N-methyl-D-aspartate (NMDA) ionotropic glutamate receptor. Esketamine nasal spray offers a new mechanism of action to treat MDD, in a therapy area that has had little innovation since the introduction of SSRIs or SNRIs over 30 years ago.[viii]

 

The SMC made its decision based on data from the robust Phase 3 clinical trial programme evaluating the safety and efficacy of esketamine in patients with TRD. Results from the Phase 3 study TRANSFORM-2 show that in adults (aged 18 to 64 years) with treatment resistant depression, esketamine nasal spray plus newly initiated oral antidepressant significantly reduced (p=0.02) the Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline to week 4 compared with placebo nasal spray plus newly initiated oral antidepressant.[ix] In another trial, SUSTAIN-1, it was also shown that patients who received esketamine nasal spray plus oral antidepressant have lower rate of relapse compared to placebo nasal spray plus oral antidepressant.[x]

 

The safety profile of esketamine nasal spray was also evaluated across all Phase 3 studies and one Phase 2 study. The most commonly observed adverse reactions in TRD patients treated with esketamine nasal spray were dizziness, nausea, dissociation, headache, somnolence, vertigo, dysgeusia, hypoaesthesia, and vomiting. These side effects were generally mild-to-moderate, transient (resolving within 2 hours) and happened on the day of dosing. ^{[xi] ,[xii],[xiii] xiv]}

 

The SMC’s advice applies only in the context of an approved NHS Scotland Patient Access Scheme (PAS) arrangement. Eligible patients in England and Wales will not have access to the treatment as the NICE technology appraisal process is ongoing for esketamine nasal spray.

 

Esketamine nasal spray is a controlled drug which is intended to be self-administered by the patient in a clinical setting only, under the direct supervision of a healthcare professional. Risk of harm and abuse is minimised through safe storage, provision of a single-use disposable nasal spray device, which prevents multi-use and safeguards against more than one dose of the drug being delivered in a single administration, and assessment of patient risk for abuse or misuse prior to administration. A treatment session consists of nasal administration of esketamine nasal spray and a post-administration observation period. Both administration and post-administration observation of esketamine nasal spray should be carried out in an appropriate clinical setting.

 

ENDS

 

About SPRAVATO^® (esketamine) nasal spray

Esketamine nasal spray is a glutamate receptor modulator which works on the N-methyl-D-aspartate (NMDA) ionotropic glutamate receptor. It is thought that, by acting on the NMDA receptor, esketamine nasal spray increases signalling between certain cells in the brain, which may contribute to the restoration of synaptic function in these brain regions involved with the regulation of mood and emotional behaviour.[xv]^{,[xvi],—[xvii]} Esketamine is derived from part of the ketamine molecule but is appraised by health authorities, such as the European Medicines Agency (EMA) as a distinct medication, due to differences in the efficacy and safety profile. As such, it is important these terms are not used interchangeably.

 

Important safety information

Please refer to the full Summary of Product Characteristics for full prescribing and safety information for esketamine nasal spray: https://www.medicines.org.uk/emc/product/10977/smpc.

 

The European Commission (EC) granted European license authorisation for esketamine nasal spray on 19 December 2019. It is licensed for use in combination with a selective serotonin reuptake inhibitor (SSRI) or serotonin and norepinephrine reuptake inhibitor (SNRI), for adults living 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.^[xviii]

 

Adverse events should be reported. ▼This medicinal product is subject to additional monitoring and it is therefore important to report any suspected adverse events related to this medicinal product. Reporting forms and information can be found at www.yellowcard.mhra.gov.uk or search for MHRA Yellow Card in the Google Play or Apple App Store. Adverse events should also be reported to Janssen-Cilag Limited on 01494 567447 or at dsafety@its.jnj.com.

 

About Major Depressive Disorder (MDD) and Treatment Resistant Depression (TRD)

Major depressive disorder (MDD) is a severe and chronic mood disorder that can have a profound and devastating impact on those affected, as well as their carers, families and loved ones around them.[xix]^,[xx] It causes severe and persistent symptoms of depression which can affect almost every aspect of a person’s life.¹⁹ Treatment-resistant depression (TRD) is defined as an inadequate response to two or more currently available treatments with antidepressants in a single, current episode of moderate-to-severe depression. Up to 30 per cent of people who suffer from MDD do not respond to treatment and are considered to have TRD.⁴

 

According to the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders 5^th edition, American Psychiatric Association, 2013) MDD is diagnosed when at least 5 symptoms of depression, which must include depressed mood and/or loss of interest or pleasure in activities, cause clinically significant distress or impaired functioning almost every day for at least a 2-week period.¹⁹ Other symptoms may also include: irritability, disturbances in sleep, appetite or sexual desire, constipation, suicidal thoughts and slowing of speech and action.^19,[xxi]

 

Although MDD is diagnosed when symptoms are present for at least 2 weeks, episodes usually last significantly longer – months or even years, so people living with MDD may delay seeking help.

 

The impact of Major Depressive Disorder (MDD) and Treatment Resistant Depression (TRD)

Depression, including MDD and TRD, represent a substantial burden both for patients and the wider society. Research suggests patients with TRD are impacted by multiple negative health outcomes including poorer health-related quality of life, higher work productivity loss and increased healthcare use including hospitalisations, compared to the general population.^5,[xxii] In addition, this critical unmet health need carries a significant societal and economic burden.

 

About the Janssen Pharmaceutical Companies of Johnson & Johnson

At Janssen, we’re creating a future where disease is a thing of the past. We’re the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular & Metabolism, Immunology, Infectious Diseases & Vaccines, Neuroscience, Oncology, and Pulmonary Hypertension.

 

Janssen-Cilag Limited is a Janssen Pharmaceutical Company of Johnson & Johnson. Learn more at www.janssen.com/uk. Follow us at www.twitter.com/JanssenUK.

 

Cautions Concerning Forward-Looking Statements

This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding SPRAVATO^® (esketamine) nasal spray. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialise, actual results could vary materially from the expectations and projections of Janssen-Cilag Limited, any of the other Janssen Pharmaceutical Companies and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behaviour and spending patterns of purchasers of healthcare products and services; changes to applicable laws and regulations, including global healthcare reforms; and trends toward healthcare cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended December 29, 2019, including in the sections captioned “Cautionary Note Regarding Forward-Looking Statements” and “Item 1A. Risk Factors,” and in the company’s most recently filed Quarterly Report on Form 10-Q, and the company’s subsequent filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. Neither the Janssen Pharmaceutical Companies nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.     

 

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EM-40927

Date of preparation: September 2020

 

References

 

[i] Scottish Medicines Consortium. Esketamine (Spravato) – SMC2258. Available at: https://www.scottishmedicines.org.uk/medicines-advice. Accessed September 2020.

[ii] Ionescu, D. F., Rosenbaum, J. F., & Alpert, J. E. (2015). Pharmacological approaches to the challenge of treatment-resistant depression. Dialogues in clinical neuroscience, 17(2), 111–126.

[iii] Woo J, et al. (2011) Impact of depression on work productivity and its improvement after outpatient treatment with antidepressants. Value Health;14(4):475-82.

[iv] Al-Harbi KS. (2012) Treatment-resistant depression: therapeutic trends, challenges and future directions. Patient Pref Adherence;6:369–388.

[v] Knoth RL et al. (2010) Effect of inadequate response to treatment in patients with depression. Am J Manag Care; 16:e188-96

[vi] Üstün, T., & Kessler, R. (2002) Global burden of depressive disorders: The issue of duration. British Journal of Psychiatry;181(3):181-183.

[vii] Trivedi MH, et al. (2004) The Link Between Depression and Physical Symptoms. Prim Care Companion J Clin

Psychiatry;6(Suppl 1):12-16.

[viii] Lener MS, Kadriu B and Zarate Jr C. (2017) Ketamine and Beyond: Investigations into the potential of glutamatergic agents to treat depression. Drugs; 77:381-401.

[ix] Popova V, et al. (2019) Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study. Am J Psychiatry;176(6):428-43.

[x] Daly E et al. (2019) Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression: A Randomized Clinical Trial. JAMA Psychiatry. 76(9):893-903.

[xi] Wajs E, Alusio L, Morrison R, et al. (2020). Esketamine Nasal Spray Plus Oral Antidepressant in Patients With Treatment-Resistant Depression: Assessment of Long-Term Safety in a Phase 3, Open-Label Study (SUSTAIN-2). J Clin Psychiatry; 81(3):19m12891.

[xii] Ochs-Ross R, Daly E, Zhang Y, et al.(2019) Efficacy and safety of esketamine nasal spray plus an oral antidepressant in elderly patients with treatment-resistant depression. The American Journal of Geriatric Psychiatry; 28(2):121 – 141.

[xiii] Fedgchin M, et al. (2019) Efficacy and Safety of Fixed-Dose Esketamine Nasal Spray Combined With a New Oral Antidepressant in Treatment-Resistant Depression: Results of a Randomized, Double-Blind, Active-Controlled

Study (TRANSFORM-1). Int J neuropsychopharmacol;22(10):616-630.

[xiv] Daly E, Singh J, Fedgchin M et al. (2018) Efficacy and safety of intranasal esketamine adjunctive to oral antidepressant therapy in treatment-resistant depression. JAMA Psychiatry; 75 (2): 139-148.

[xv] Lener MS, et al. (2017) Ketamine and Beyond: Investigations into the potential of glutamatergic agents to treat depression. Drugs; 77:381-401.

[xvi] Duman R, (2018) Ketamine and rapid-acting antidepressants: a new era in the battle against depression and suicide. F1000 Research; 7:659.

[xvii] Duman R, (2014) Pathophysiology of depression and innovative treatments: remodeling glutamatergic synaptic connections. Dialogues Clin Neurosci;16(1):11-27.

[xviii] European Medicines Agency. Available at: https://www.ema.europa.eu/documents/product-information/spravato-epar-product-information_en.pdf. Accessed September 2020.

[xix] American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing.

[xx] Shah AJ, et al. (2010) Psychological Distress in Carers of People with Mental Disorders. BJMP;3(3):a327.

[xxi] Habert J et al. (2016) Functional Recovery in Major Depressive Disorder: Focus on Early Optimized Treatment. Prim Care Companion CNS Disord; 18(5).

[xxii] Johnston K et al. (2019) The burden of treatment-resistant depression: A systematic review of the economic and quality of life literature. J Affect Disord;242:195-210.