TITUSVILLE, N.J. – (August 3, 2020) – The Janssen Pharmaceutical Companies of Johnson & Johnson today announced that the U.S. Food and Drug Administration (FDA) has approved the supplemental new drug application (sNDA) for Spravato (esketamine) CIII nasal spray, taken with an oral antidepressant, to treat depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior.¹ Spravato is the first and only approved medicine that has been shown to reduce depressive symptoms within 24 hours,¹ providing a new option for significant symptom relief until a longer-term, comprehensive treatment plan can take effect.

The effectiveness of Spravato in preventing suicide or in reducing suicidal ideation or behavior has not been demonstrated. Use of Spravato does not preclude the need for hospitalization if clinically warranted, even if patients experience improvement after an initial dose of Spravato. Spravato carries a Boxed Warning regarding a Risk Evaluation and Mitigation Strategy (REMS) and the risk of suicidal thoughts and behaviors. See below for Important Safety Information. Spravato will be made available at REMS certified treatment centers. Janssen is working to responsibly educate and certify treatment centers in accordance with the REMS so healthcare providers can offer Spravato to appropriate patients.

Depression is the leading cause of disability worldwide and the condition most frequently associated with suicide.² MDD is a serious disease that causes a significant, negative impact on the way people think, feel and act.³ Symptoms and severity vary by person and may include persistent feelings of sadness, hopelessness or tension; changes in sleep or appetite; difficulty concentrating or performing activities of daily living; lack of interest; and/or thoughts of harming themselves.³

“Many people who live with depression know all too well the feeling of desperation. If that major depression progresses to active suicidal thoughts, it’s crushing, and they need options to help change the trajectory of their acute depressive episode,” said Theresa Nguyen, Chief Program Officer, Mental Health America. “Traditional oral antidepressants need weeks or more to take effect, so the availability of a medicine that can begin providing relief within a day is potentially life changing.”

The sNDA approval is based on two identical Phase 3 clinical trials in which Spravato plus comprehensive standard of care demonstrated a significant, rapid reduction of depressive symptoms within 24 hours, with some patients starting to respond as early as four hours. Spravato plus comprehensive standard of care led to a 15.9 and 16.0 point decrease on the Montgomery-Åsberg Depression Rating Scale (MADRS), a tool used to assess severity of depressive symptoms, in the two trials at 24 hours after the first dose of study medication. This compared to a reduction of 12.0 and 12.2 points in the placebo plus comprehensive standard of care group. The comprehensive standard of care included initial hospitalization, a newly initiated or optimized oral antidepressant and twice-weekly treatment visits for four weeks, during which patients received Spravato 84 mg or placebo nasal spray.^4,5

Both the Spravato and placebo groups continued to improve between four hours and 25 days, with 41 percent and 43 percent of the Spravato plus comprehensive standard of care group achieving clinical remission of depression (minimal or no symptoms) compared with 34 percent and 27 percent in the placebo groups, by the end of the double-blind period, in the two trials, respectively.^4,5

“It is astonishing to me that despite what we know about the risk of serious suicidal ideation in the context of major depression, patients with suicidal ideation have previously been excluded from nearly all studies examining antidepressant treatment efficacy. There is an immense need for high quality evidence showing effective and rapid antidepressant action in this population,” said Gerard Sanacora,* Ph.D., M.D., Director, Yale Depression Research Program, Co-Director, Yale New Haven Hospital Interventional Psychiatry Service, and esketamine clinical trial investigator. “The clinical trials supporting this new indication provide compelling evidence that esketamine may offer clinicians a new way to provide support to patients quickly in the midst of an urgent depressive episode and help set them on the path to remission.”

In the two Phase 3 trials, improvement in the severity of suicidality at 24 hours was measured using a standardized global scale. The treatment difference between the two groups was not statistically significant on this key secondary endpoint. Both Spravato and placebo in combination with comprehensive standard of care showed a similar reduction on this measure.^4,5

The safety profile observed in the trials was consistent with previous studies of Spravato in treatment-resistant depression (TRD), adding to the established body of safety and efficacy evidence. The most common side effects included dissociation (feeling disconnected from yourself, your thoughts, feelings, space and time), dizziness, sedation (sleepiness), increased blood pressure, hypoesthesia, vomiting, euphoric mood and vertigo.¹

With this new indication, Spravato can be prescribed to treat depressive symptoms in two MDD subpopulations of adults with high unmet need:

• TRD, which the FDA approved on March 5, 2019, and
• MDD with acute suicidal ideation or behavior.¹

A full course of treatment for the new indication is twice weekly for four weeks, after which evidence of therapeutic benefit should be evaluated to determine need for continued treatment.

“People living with major depression need more options to meet their most critical needs, and we’re proud to help redefine how we treat ongoing and acutely worsening depressive symptoms,” said Bill Martin, Global Therapeutic Area Head, Neuroscience, Janssen Research & Development, LLC. “Spravato can now help patients with challenging to treat depression find significant and swift relief from debilitating depressive symptoms, offering those living with this serious mental health condition the possibility of a better future.”

Once Spravato is determined as an appropriate treatment option, in accordance with the REMS, patients will be treated at a certified treatment center trained to administer the medicine and address their needs. Janssen will educate healthcare providers and payers on this updated label to ensure appropriate patients are evaluated and the full course of treatment is delivered in a safe, appropriate and controlled manner for patients to receive the maximum treatment benefit.

For patients who need help getting started on Spravato and staying on track, Janssen CarePath offers a comprehensive support program. Janssen CarePath provides information on insurance coverage, potential out-of-pocket costs and treatment support, and identifies options that may help make treatment more affordable, including the Janssen CarePath Savings Program for commercially insured patients who are eligible. Those who don’t have commercial or private health insurance, or who aren’t eligible for the Janssen CarePath Savings Program, can visit JanssenPrescriptionAssistance.com for more information about other resources that may help with their out-of-pocket medication costs.

*Dr. Sanacora has received research support from Janssen and has served as a paid consultant to the company.

About Spravato

Spravato (esketamine) CIII nasal spray is a non-selective, non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor – an ionotropic glutamate receptor. It has a novel mechanism of action, meaning it works differently than currently available therapies for major depressive disorder (MDD).

Spravato is approved in the United States, in conjunction with an oral antidepressant, to treat adults with treatment-resistant depression (TRD) and depressive symptoms in adults with MDD with acute suicidal ideation or behavior. Spravato has been submitted for health authorities’ review for TRD and adults with MDD who have current suicidal ideation with intent in other markets around the world, including Europe. The FDA granted Breakthrough Therapy Designation to esketamine nasal spray for TRD in November 2013 and for MDD with imminent risk for suicide in August 2016.

About the Spravato® Risk Evaluation & Mitigation Strategy (REMS)
A REMS program is in place to ensure the safety of all patients who are treated with Spravato. Spravato is available only through a restricted distribution program called the Spravato REMS. The goals of the REMS are to mitigate the risks of serious adverse outcomes resulting from sedation and dissociation caused by Spravato administration, and abuse and misuse of Spravato, by:

• Ensuring Spravato is only dispensed and administered to patients in medically supervised healthcare settings that monitor these patients
• Ensuring pharmacies and healthcare settings that dispense Spravato are REMS certified
• Ensuring each patient is informed about serious adverse outcomes from dissociation and sedation and the need for monitoring
• Enrolling all patients who receive treatment in an outpatient healthcare setting in a REMS registry to further characterize the risks and support safe use

About the Phase 3 Studies^4,5
ASPIRE I and ASPIRE II evaluated the efficacy and safety of Spravato in addition to a comprehensive standard of care in adult patients with major depressive disorder who had active suicidal ideation with intent. This is the first global clinical program to study this severely ill patient population, who have been typically excluded from antidepressant clinical trials, addressing a great unmet need. Patients were defined as those with major depression and active suicidal thoughts with intent. Every patient was treated with a comprehensive standard of care in both trials to safely and ethically conduct the studies. The comprehensive standard of care included initial hospitalization, a newly initiated or optimized oral antidepressant and twice-weekly treatment visits for four weeks.

The primary efficacy endpoint of the double-blind, randomized, placebo-controlled, multicenter studies was a reduction in depressive symptoms at 24 hours after the first dose, as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS). The MADRS scale is a tool used to assess severity of depressive symptoms, allowing clinicians to evaluate 10 symptoms on a six-point scale to produce a total score of up to 60 points. A secondary efficacy endpoint measured improvement in severity of suicidality as measured by the revised Clinical Global Impression of Severity of Suicidality (CGI-SS-r), a seven-point scale developed by clinical experts that is a measure of the severity of suicidality as judged by the clinician’s global impression.

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. Follow us at www.twitter.com/JanssenUS. Janssen Pharmaceuticals, Inc. is one 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) CIII 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 materialize, actual results could vary materially from the expectations and projections of OPCO, 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 behavior 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.

1. 1 SPRAVATO® [Prescribing Information]. Titusville, N.J., Janssen Pharmaceuticals, Inc. July 2020.
   2 World Health Organization. Media Centre: Depression. Available at: http://www.who.int/news-room/fact-sheets/detail/depression. Accessed July 21, 2020.
2. 3 National Institute of Mental Health. Depression. Available at: https://www.nimh.nih.gov/health/topics/depression/index.shtml. Accessed July 21, 2020.
   4 Dong-Jing Fu et al. J Clin Psych. 2020.
   5 Dawn Ionescu, Carla Canuso, Dong-Jing Fu, et al. Esketamine nasal spray for rapid reduction of major depressive disorder symptoms in patients at imminent risk for suicide: ASPIRE-2 study. Presented at European College of Neuropsychopharmacology (ECNP) Congress; September 2019; Copenhagen, Denmark.

Source: Janssen Pharmaceutical Companies of Johnson & Johnson

Posted: August 2020

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