Johnson & Johnson’s investigational seltorexant shows numerically higher response in patients with depression with insomnia symptoms, with fewer side effects compared to quetiapine XR

TITUSVILLE, NJ. (September 22, 2025) – Johnson & Johnson announced results from the Phase 3 MDD3005 26-week clinical trial evaluating the efficacy and safety of seltorexant compared to quetiapine extended release (XR) as an adjunctive treatment in adult and elderly patients with major depressive disorder (MDD) with insomnia symptoms. The findings were presented at this year’s annual U.S. Psychiatric and Mental Health Congress (Psych Congress), held from September 17-21 in San Diego, California. Seltorexant is an investigational, first-in-class selective antagonist of the human orexin-2 receptor being studied for the adjunctive treatment of MDD with insomnia symptoms. The Phase 3 randomized, double-blind, parallel-group study showed a numerically greater response rate at 26 weeks with seltorexant than quetiapine XR (57.4 percent versus 53.4 percent), a commonly prescribed adjunctive therapy for MDD patients experiencing insomnia symptoms, though this difference did not reach statistical significance for the primary endpoint.1Seltorexant and quetiapine XR showed large and clinically meaningful improvements in depressive symptoms (-23.0 and -22.7, respectively), as measured by change in Montgomery-Asberg Depression Rating Scale (MADRS) total score from baseline. Seltorexant was also safe and well-tolerated, with common adverse events consistent with previous seltorexant clinical trials. Patients treated with seltorexant experienced considerably fewer side effects than those treated with quetiapine XR, with more patients completing the 26-week study period. Somnolence with seltorexant occurred at a rate four times lower than with quetiapine XR (6 percent versus 24 percent, respectively), and patients experienced notably less weight gain with seltorexant, seeing an average increase of 0.5 kg (1.1 lb.) compared to 2.1 kg (4.6 lb.) with quetiapine XR. “Although the study did not meet its primary endpoint, seltorexant showed efficacy comparable to quetiapine XR, a medication with proven efficacy for MDD that is often associated with notably challenging side effects for patients, such as weight gain and over-sedation.2These findings are particularly important, as many patients discontinue treatment due to side effects,3” said Andrew Cutler, M.D., Chief Medical Officer, National Educational Institute and Associate Clinical Professor of Psychiatry at the SUNY Upstate Medical Hospital.a“Seltorexant has the potential to help address a persistent treatment gap in MDD, particularly for the nearly 60 percent of patients who continue to experience residual insomnia symptoms while on an antidepressant.4” The results from this study were observed in a patient population that was assessed to be moderately-to-severely depressed and suffered from clinically relevant insomnia symptoms. Depression and insomnia symptoms are closely linked, with patients often experiencing both simultaneously.5Insomnia symptoms, such as trouble falling asleep, staying asleep or getting good quality sleep, can worsen depression.4,6This can lead to a frustrating cycle for patients – creating a bidirectional relationship where their depression leads to sleep disturbances, which in turn worsens their depression. Currently, no therapies are approved to help treat MDD with insomnia symptoms. “With a potential first-in-class mechanism of action, seltorexant represents a promising advancement in the treatment of MDD,” said Bill Martin, Ph.D., Global Therapeutic Area Head, Neuroscience, Johnson & Johnson Innovative Medicine. “Together with existing positive Phase 3 data, these results reinforce the value seltorexant may bring by offering patients meaningful symptom relief without a considerable compromise on tolerability.” Other accepted data at Psych Congress showcased Johnson & Johnson’s ongoing commitment to advancing treatment and care for people living with some of today’s most prevalent and debilitating neuropsychiatric disorders. A complete listing of Company-sponsored abstracts can be viewedhere. Editor’s note: aAndrew Cutler, M.D., has provided consulting, advisory, and speaking services to Johnson & Johnson. He has not been paid for any media work. 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 symptoms associated with depression and restoring sleep without next-day sedation in patients 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. Seltorexant is the only investigational therapy being studied in MDD that is believed to work by normalizing the overactivation of the orexin-2 receptors, thereby addressing the underlying biology that contributes to depression and insomnia symptoms. About MDD3005 The Phase 3 MDD3005 study was a randomized, double-blind, parallel-group study designed to evaluate the efficacy and safety of seltorexant 20 milligrams compared to quetiapine extended release (XR) as adjunctive therapy to a current SSRI or SNRI 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, with an estimated 332 million people living with the disorder around the world.7,8MDD often includes sleep disturbances such as insomnia or hypersomnia, with approximately 60 percent of MDD patients experiencing insomnia symptoms despite being on an SSRI/SNRI.4Disturbed sleep and insomnia symptoms have a significant impact on a patient’s quality of life and exacerbate the risk of depressive relapse and suicide.9,10,11 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 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 athttps://www.jnj.com/or atwww.innovativemedicine.jnj.com.Follow us at@JNJInnovMed. © Johnson & Johnson and its affiliates 2025. All rights reserved. Cautions Concerning Forward-Looking Statements This press release contains “forward-looking statements” as defined in the Private Securities Litigation Reform Act of 1995 related to seltorexant. 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 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 most recent Annual Report on Form 10-K, 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 Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com, www.investor.jnj.com or on request from Johnson & Johnson. Johnson & Johnson does not undertake to update any forward-looking statement as a result of new information or future events or developments. Footnotes 1Chopra A. Treatment Strategies for Managing Insomnia in MDD. Pharmacology Institute. Published December 1, 2023. https://psychopharmacologyinstitute.com/section/treatment-strategies-for-managing-insomnia-in-mdd-2765-5607 2MedlinePlus. Quetiapine. Published June 15, 2020. https://medlineplus.gov/druginfo/meds/a698019.html 3Niarchou E, Roberts L, Naughton BD. What is the impact of antidepressant side effects on medication adherence among adult patients diagnosed with depressive disorder: A systematic review. Journal of Psychopharmacology. 2024;38(2):127-136. doi:https://doi.org/10.1177/02698811231224171 ‌ 4Ohayon MM, Roth T. Place of chronic insomnia in the course of depressive and anxiety disorders. J Psychiatr Res. 2003;37(1):9-15. doi:10.1016/S0022-3956(02)00052-3 5Riemann D, Berger M, Voderholzer U. Sleep and depression—results from psychobiological studies: an overview. Biol Psychol. (2001) 57:67–103. 6Nutt D, Wilson S, Paterson L. Sleep disorders are core symptoms of depression. Dialogues Clin Neurosci. 2008 Sep; 10(3): 329–336. 7World Health Organization. “Depression: let’s talk” says WHO, as depression tops list of causes of ill health. March 30, 2017. 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 8World Health Organization. Depressive disorder (depression). March 31, 2023. Available at: https://www.who.int/news-room/fact-sheets/detail/depression 9Chopra, 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 10Chow 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. Available at: https://www.ajmc.com/view/economic-burden-mdd 11Taddei-Allen P. Economic Burden and Managed Care Considerations for the Treatment of Insomnia. AJMC. 2020 Apr 12. Available at:https://www.ajmc.com/view/economic-burden-and-managed-care-considerations-for-the-treatment-of-insomnia Media contact: Caitlin Lormel [email protected] Investor contact: Lauren Johnson [email protected] Discover J&J News Our Credo & our purpose Leadership Social impact Suppliers Our history Policies & reports Environmental sustainability Medicines & therapies Products Oncology Immunology Neuroscience Cardiopulmonary Medical devices & technology Products Cardiovascular Orthopaedics Surgery Vision About us Our company Medicines & therapies Medical devices & technology Careers Investors Media Key links Terms of use Privacy Cookie policy Customize cookie settings Digital Accessibility Statement Get in touch Contact Socials linkedin instagram facebook twitter This website is intended for U.S. audiences only. Do not sell or share my personal information Limit the use of my sensitive personal information © Johnson & Johnson and its affiliates 2026

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