Johnson & Johnson Pivotal Study of Seltorexant Shows Statistically Significant and Clinically Meaningful Improvement in Depressive Symptoms and Sleep Disturbance Outcomes

The Phase 3 randomized, double-blind, multicenter, placebo-controlled study achieved all primary and secondary endpoints, with seltorexant demonstrating both a statistically significant and clinically meaningful improvement in depressive symptoms based on the Montgomery-Asberg Depression Rating Scale (MADRS) total score at day 43, and improved sleep disturbance outcomes, in patients who had a prior inadequate response to SSRI/SNRI antidepressants alone. These results were observed in a patient population that was assessed to be moderately-to-severely depressed despite ongoing treatment with SSRI/SNRIs and suffered from significant sleep disturbance. Seltorexant was also safe and well-tolerated in the study, with similar rates of common adverse events seen in both trial arms, consistent with previous seltorexant clinical trials.

“Depression is a leading cause of disability worldwide and shares a strong link with sleep disturbances. In MDD, insomnia symptoms exacerbate the risk of depressive relapse, increase healthcare costs and impact quality of life, and it often goes under treated despite being one of the most common residual symptoms^2,3,4,” said Andrew Krystal, MD, Professor, Psychiatry, University of California, San Francisco Weill Institute for Neurosciences. “Seltorexant has the potential to fill a significant unmet need for new therapies to treat patients experiencing depression and insomnia, and most importantly, to improve outcomes and quality of life for these patients.”

MDD is often accompanied by sleep disturbances such as insomnia or hypersomnia. With insomnia, patients may have trouble falling asleep, staying asleep, or getting good quality sleep. Approximately 60 percent of MDD patients on standard-of-care oral antidepressants experience residual insomnia symptoms.¹ Currently, no therapies are approved to treat MDD with insomnia symptoms.

“For nearly seven decades, Johnson & Johnson has delivered transformational treatments and solutions for people living with serious mental illness, and we are proud to present these data from our marketed and late-stage neuropsychiatry portfolios at ASCP,” said Bill Martin, Ph.D., Global Therapeutic Area Head, Neuroscience. “As global leaders, we must continue to drive innovation in the treatment of depression, bringing new mechanisms of action and potentially first-in-class therapies to the millions of people living with mental health disorders.”

DELIVERING RAPID AND SUSTAINED EFFICACY FOR TREATMENT-RESISTANT DEPRESSION (TRD)
Additional data presented at ASCP includes positive topline results from the placebo-controlled Phase 4 TRD4005 study of SPRAVATO^® (esketamine) CIII nasal spray as a monotherapy in patients with TRD, which met both its primary and secondary endpoints. The randomized, double-blind, multicenter study showed SPRAVATO^® provided rapid, statistically significant, and clinically meaningful improvement in depressive symptoms ~24 hours after the first dose and sustained through 4 weeks of treatment, as assessed by changes in MADRS total score.

The safety profile of SPRAVATO^® monotherapy was consistent with the registration Phase 3 studies of TRD in combination with an oral antidepressant, and no new safety concerns were identified.

SPRAVATO^® is approved by the U.S. Food and Drug Administration (FDA), in combination with an oral antidepressant, for adults with TRD and depressive symptoms in adults with MDD with suicidal thoughts or behaviors. With its approval in 2019, SPRAVATO^® offered the first novel mechanism of action in decades for the treatment of MDD. To date, SPRAVATO^® has been administered to more than 100,000 people living with challenging-to-treat forms of depression around the world.

ABOUT SELTOREXANT
Seltorexant, an investigational first-in-class therapy, is a selective antagonist of the human orexin-2 receptor currently being developed as an adjunctive treatment for adults with MDD with insomnia symptoms. Seltorexant selectively antagonizes the orexin-2 receptors, potentially improving mood and sleep symptoms associated with depression. When orexin-2 receptors are stimulated for too long or at inappropriate times, their activation can cause hyperarousal manifestations, including insomnia and excessive cortisol release, which may contribute to depression and insomnia.

ABOUT MDD3001
The Phase 3 MDD3001 study was a randomized, double-blind, multicenter, placebo-controlled study designed to compare the efficacy and safety of oral, once daily seltorexant 20 milligrams to that of placebo, adjunctive to background SSRI/SNRI, for improving depressive symptoms in adult and elderly patients with MDD with insomnia symptoms.

ABOUT MAJOR DEPRESSIVE DISORDER WITH INSOMNIA SYMPTOMS
MDD is one of the most common psychiatric disorders and leading causes of disability worldwide,⁵ with an estimated 280 million people living with the disorder around the world.⁶ MDD is often accompanied by sleep disturbances such as insomnia or hypersomnia, with approximately 60 percent of MDD patients experiencing insomnia symptoms despite being on an SSRI/SNRI.¹ Disturbed sleep and insomnia symptoms have a significant impact on a patient’s quality of life and exacerbate the risk of depressive relapse and suicide.^2,4

ABOUT SPRAVATO^®
SPRAVATO^® (esketamine) CIII nasal spray is approved by the U.S. Food and Drug Administration in combination with an oral antidepressant for adults with TRD and depressive symptoms in adults with major depressive disorder with acute suicidal ideation or behavior. It is the first novel mechanism of action in decades for the treatment of MDD. SPRAVATO^® is a non-selective, non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor and is believed to work differently by acting on a pathway in the brain that affects glutamate. To date, SPRAVATO^® has been approved in 77 countries and administered to more than 100,000 patients worldwide.

ABOUT TRD4005
The Phase 4 TRD4005 clinical trial was a randomized, double-blind, multicenter, placebo-controlled study designed to evaluate the efficacy, safety, and tolerability of esketamine monotherapy at either 56 milligrams or 84 milligrams, administered bi-weekly, compared with placebo nasal spray in improving depressive symptoms in adult patients with TRD.

ABOUT TREATMENT-RESISTANT DEPRESSION
It is estimated that at least 30 percent of people living with MDD have treatment-resistant depression, which is defined as not responding to at least two or more different antidepressants of adequate dose and duration.⁷ TRD has a significant negative impact, emotionally and functionally, on the individual and their loved ones, and has one of the highest economic burdens of all psychiatric disorders.⁷

ABOUT JOHNSON & JOHNSON
At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and where solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity.

Learn more at http://www.jnj.com or at https://www.janssen.com/johnson-johnson-innovative-medicine. Follow us at @JNJInnovMed.

Janssen Research & Development, LLC and Janssen Biotech, Inc. are both Johnson & Johnson companies.

CAUTIONS CONCERNING FORWARD-LOOKING STATEMENTS
This press release contains “forward-looking statements” as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits and treatment impact of seltorexant and SPRAVATO^®. 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 Janssen Research & Development, LLC, Janssen Biotech, Inc., 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 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 31, 2023, including in the sections captioned “Cautionary Note Regarding Forward-Looking Statements” and “Item 1A. Risk Factors,” and in Johnson & Johnson’s subsequent Quarterly Reports on Form 10-Q and other filings with the U.S. 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 Janssen Research & Development, LLC, Janssen Biotech, Inc. nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.

© Johnson & Johnson 2024. All rights reserved.

1. Emery PC, Wilson KG, Kowal J. Major depressive disorder and sleep disturbance in patients with chronic pain. Pain Res Manag. Jan-Feb 2014;19(1):35-41. doi: 10.1155/2014/480859

2. Chopra, A. (2023, December 1). Understanding the Relationship Between Insomnia Disorder and MDD. Psychopharmacology Institute. https://psychopharmacologyinstitute.com/section/understanding-the-relationship-between-insomnia-disorder-and-mdd-2765-5602

3. Chow W et al. Economic Burden Among Patients With Major Depressive Disorder: An Analysis of Healthcare Resource Use, Work Productivity, and Direct and Indirect Costs by Depression Severity. AJMC. 2019 Feb 2014. Link: https://www.ajmc.com/view/economic-burden-mdd

4. Taddei-Allen P. Economic Burden and Managed Care Considerations for the Treatment of Insomnia. 2020 Apr 12. Link: https://www.ajmc.com/view/economic-burden-and-managed-care-considerations-for-the-treatment-of-insomnia.

5. World Health Organization. “Depression: let’s talk” says WHO, as depression tops list of causes of ill health. March 30, 2017. Accessed April 2024. Available at: https://www.who.int/news/item/30-03-2017--depression-let-s-talk-says-who-as-depression-tops-list-of-causes-of-ill-health

6. World Health Organization. Depressive disorder (depression). March 31, 2023. Accessed April 2024. Available at: https://www.who.int/news-room/fact-sheets/detail/depression

7. Zhdanava M, Pilon D, Ghelerter I, et al. The prevalence and national burden of treatment-resistant depression and major depressive disorder in the United States. J Clin Psychiatry. 2021;82(2):20m13699.

Source: Johnson & Johnson