Janssen Receives Positive CHMP Opinion for SPRAVATO? (Esketamine Nasal Spray) for the Rapid Reduction of Depressive Symptoms in a Psychiatric Emergency for Patients with Major Depressive Disorder

• Positive opinion is based on results from two Phase 3 ASPIRE studies in adult patients with moderate to severe Major Depressive Disorder (MDD) with current/active suicidal ideation with intent, designed to evaluate the efficacy and safety of esketamine nasal spray used in addition to comprehensive standard of care (SOC)^1,2
• In ASPIRE studies, rapid reduction in depressive symptoms was seen as early as four hours after an initial dose of esketamine nasal spray^1,2

The Janssen Pharmaceutical Companies of Johnson Johnson announced today that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended the expanded use of SPRAVATO (esketamine nasal spray) co-administered with oral antidepressant therapy in adults with a moderate to severe episode of MDD, as acute short term treatment, for the rapid reduction of depressive symptoms, which according to clinical judgement constitute a psychiatric emergency.³

"Immediate intervention for individuals living with Major Depressive Disorder who are in a psychiatric emergency is essential," said Allitia DiBernardo, MD, European Therapeutic Area Lead for Mood Disorders, Janssen-Cilag. "Whilst currently available antidepressants are effective in treating depressive symptomatology, they can often take weeks to achieve their full effects, which limits their utility in acute, emergency treatment."

The European marketing authorisation application was based on the Phase 3 double-blind, randomised, placebo controlled, multicentre ASPIRE I II clinical studies conducted across Europe. 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.^1,2 The comprehensive SOC included initial psychiatric hospitalisation and newly initiated or optimised oral antidepressant therapy, which was determined by the treating physician based on clinical judgement and practice guidelines, for the duration of the studies.^1,2

Across both studies, patients treated with esketamine nasal spray accompanied by comprehensive SOC had a statistically significant and clinically meaningful reduction in depressive symptoms (reduction from baseline Montgomery-Åsberg Depression Rating Scale [MADRS] total score) at 24 hours after receiving the first dose compared to placebo nasal spray in combination with comprehensive SOC (p=0.006). The benefit of esketamine nasal spray plus comprehensive SOC on symptoms of MDD was apparent as early as 4 hours after the first dose.^1,2 The effectiveness of esketamine nasal spray in preventing suicide or in reducing suicidal ideation or behaviour has not been demonstrated.

The safety profile of esketamine nasal spray in this patient population was consistent with previous studies in adults with treatment-resistant depression (TRD).^4,5 The most common treatment-emergent adverse events (=20%) observed in the esketamine nasal spray plus comprehensive SOC group versus the placebo nasal spray plus comprehensive SOC group during the double-blind phase were dizziness (38.3% vs 13.8%), dissociation (33.9% vs 5.8%), nausea (26.9% vs 13.8%), somnolence (20.7% vs 10.2%), and headache (20.3% vs 20.4%), respectively.⁶

"There is a pressing need to provide individuals with Major Depressive Disorder who are experiencing a psychiatric emergency with treatments that can rapidly reduce their depressive symptoms," said Bill Martin, Ph.D., Global Therapeutic Area Head, Neuroscience, Janssen Research Development, LLC. "If approved by the European Commission, esketamine nasal spray has the potential to offer individuals relief from debilitating depressive symptoms and address a key unmet need within this population."

With this positive CHMP opinion, esketamine nasal spray will now be considered by the European Commission for adults with a moderate to severe episode of MDD, as acute, short term treatment, for the rapid reduction of depressive symptoms, which according to clinical judgement constitute a psychiatric emergency. The European Commission has the authority to grant marketing authorisation for medicines in the European Economic Area.

The Montgomery-Åsberg Depression Rating Scale (MADRS): A 10-item diagnostic questionnaire that psychiatrists use to measure the severity of depressive episodes in patients with mood disorders

ENDS#

About esketamine nasal spray

As an antagonist of the N-methyl-D-aspartate (NMDA) glutamate receptor, esketamine nasal spray offers the first new approved mechanism of action in 30 years for an anti-depressant.^4,7-9

Esketamine nasal spray is self-administered, under the direct supervision of a healthcare professional, through a single-use nasal spray device, offering a novel mode of drug administration for the treatment of MDD. The decision to prescribe esketamine nasal spray should be determined by a psychiatrist.¹⁰

Esketamine nasal spray was approved by the European Commission for use in combination with a selective serotonin reuptake inhibitor (SSRI) or serotonin and norepinephrine reuptake inhibitor (SNRI), in adult patients with treatment-resistant major depressive disorder (TRD) in December 2019. The U.S. Food and Drug Administration (FDA) approved esketamine nasal spray for use in conjunction with an oral antidepressant, for adults living with treatment-resistant depression in March 2019 and for use in adults with major depressive disorder with acute suicidal ideation or behaviour on 31 July 2020.^11-13

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 https://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 [e-mail].

For further safety information, please see the Summary of Product Characteristics available at https://www.ema.europa.eu/en/documents/product-information/spravato-epar-product-information_en.pdf

About Major Depressive Disorder

Major depressive disorder (MDD) affects nearly 40 million people of all ages in Europe and is one of the leading causes of disability worldwide.^14,15 Individuals with depression, including MDD, experience continuous suffering from a serious, biologically-based disease, which has a significant negative impact on all aspects of life, including quality of life and function.^16,17 At its worst, MDD can be fatal, with MDD patients demonstrating a 20-fold higher risk of suicide than the rest of the population.¹⁸ Despite treatment advances, currently available antidepressant medications can take between four to six weeks to reach their full effect,and one-third of people who suffer from MDD do not respond to these treatments.^19,20

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.

Learn more at www.janssen.com/emea. Follow us at www.twitter.com/JanssenEMEA. Janssen Research Development, LLC and Janssen-Cilag International NV are part of the Janssen Pharmaceutical Companies of Johnson Johnson.

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 International NV, 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 health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care 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. None of 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.

References

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2. Ionescu D, et al.Int J Neuropsychopharmacol 2020;pyaa068.
3. Committee of Medicinal Products for Human Use (CHMP) meeting highlights. Available at: https://www.ema.europa.eu/en (last accessed December 2020).
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5. Fedgchin M, et al. Intl J Neuropsychopharmacol 2019;22(10):616-630.
6. Canuso C, et al. Presented at 58th Annual Meeting of Neuropsychopharmacology (ACNP); December 2019.
7. Hillhouse TM Porter JH. Exp Clin Psychopharmacol 2015;23(1):1-21.
8. Duman RS, et al. Nat Med 2016;22(3):238-249.
9. Newport DJ, et al. Am J Psychiatry 2015;172(10):950-966.
10. Summary of Product Characteristics. Spravato 28 mg nasal spray. Janssen-Cilag International. Last updated October 2020.
11. 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 December 2020).
12. 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 December 2020).
13. 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 December 2020).
14. 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 December 2020).
15. World Health Organization (WHO). Depression. Available at: http://www.who.int/news-room/fact-sheets/detail/depression (last accessed December 2020).
16. 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 December 2020).
17. American Psychological Association (APA). Diagnostic and Statistical Manual of Mental Disorders. 5th ed. 2013.
18. Lepine JP, et al. Neuropsychiatric Dis Treat 2011;7(suppl 1):3-7.
19. Machado-Vieira R, et al. Pharmaceuticals 2010;3(1):19-41.
20. Ionescu D, et al. Dialogues Clin Neurosci 2015;17(2):111-126.

EM-40125 December 2020

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