Nxera Pharma Receives Approval of QUVIVIQ (daridorexant) 25 and 50 mg in Japan for the Treatment of Insomnia

• The approval of QUVIVIQ™, a novel dual orexin receptor antagonist, is based on robust clinical efficacy and safety data, including from a Phase 3 trial in Japan that met all primary and secondary endpoints
• Plans to make QUVIVIQ available as soon as possible to insomnia patients in Japan are underway

Tokyo, Japan and Cambridge, UK, 24 September 2024 – Nxera Pharma Co., Ltd. (“Nxera” or “the Company”; TSE 4565) – formerly known as Sosei Group or Sosei Heptares – announces that Nxera Pharma Japan Co., Ltd. (“NPJ”) has received approval from the Ministry of Health, Labour and Welfare of Japan (“MHLW”) of its New Drug Application (“NDA”) for QUVIVIQ™ (daridorexant; ACT-541468) 25 and 50 mg for the treatment of adult patients with insomnia. The approval of QUVIVIQ, a novel dual orexin receptor antagonist, is based on robust clinical efficacy and safety data including from a dedicated Japanese Phase 3 trial. Plans to make QUVIVIQ available as soon as possible to insomnia patients in Japan are underway.

Insomnia, characterized by difficulties in sleep onset and/or sleep maintenance, is highly prevalent in Japan, affecting about 20% of Japanese adults according to the MHLW, and is recognized as an important national issue impacting both physical and mental health.

Makoto Uchiyama, M.D., Ph.D., medical advisor of the Japanese Phase 3 study, Director of Tokyo Adachi Hospital, Lecturer of Nihon University School of Medicine, and Visiting Professor of Toho University, commented: “Insomnia is highly prevalent in Japan and is recognized as an important national health issue. The disorder is not only a problem of the night but affects a patient’s ability to function during the day. QUVIVIQ is the first drug for a decade, clinically investigated in more than 100 centers in Japan, to show increased total sleep time and shortened sleep latency in patients with insomnia without marked hangover symptoms the next morning. Providing QUVIVIQ to Japanese healthcare professionals is of great significance and I believe we can change the quality of life of many patients with insomnia.”

Satoshi Tanaka, Dr Med Sci., President of Nxera Pharma Japan, and Executive Officer and Executive Vice President of Nxera Pharma, added: “We are grateful to the investigators who have cooperated in conducting clinical studies in more than 600 Japanese patients and to the patients who have participated in the trials. I also thank the Nxera Pharma Japan team, many of whom have worked on QUVIVIQ for many years and never doubted the benefit that it could bring to patients, I’m very proud of the whole team. The unique characteristics of QUVIVIQ offer patients with insomnia not only a better night sleep but also an improvement in daytime functioning. We are very pleased to bring this dual orexin receptor antagonist, QUVIVIQ, to patients with insomnia in Japan where orexin was discovered.”

The approval of QUVIVIQ by the MHLW is supported by positive results of a randomized, double-blind, placebo-controlled Phase 3 study in Japan to investigate the efficacy and safety of daridorexant. The study met all primary and secondary efficacy endpoints. Daridorexant significantly improved subjective Total Sleep Time (“sTST”), a primary endpoint defined as the change from baseline compared to placebo at 28 days (p<0.001 for 50 mg, p=0.042 for 25 mg). Daridorexant also significantly improved sleep onset as measured by a decrease in subjective Latency for Sleep Onset (“sLSO”), a primary endpoint defined as the change from baseline compared to placebo at 28 days (p<0.001 for 50 mg, p=0.006 for 25 mg). The rate of adverse events was comparable between placebo and daridorexant at both treatment doses. Treatment-emergent adverse events (“TEAEs”) during the double-blind study period were reported in 23.5% and 22.7% of the patients treated with 50 mg and 25 mg daridorexant, respectively (24.4% for placebo).

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Notes to Editors

About QUVIVIQ™
QUVIVIQ (daridorexant) is a dual orexin receptor antagonist that blocks the binding and activity of the wake-promoting neuropeptides known as orexins. In October 2022, daridorexant achieved positive Phase 3 top-line results in Japanese patients with insomnia and a New Drug Application was submitted in Japan in October 2023. Daridorexant is approved in the US and Europe and marketed in these territories under the brand name QUVIVIQ™ by Idorsia Pharmaceuticals Ltd. Nxera Pharma has the Japanese and APAC (ex-China) rights for daridorexant following its acquisition of Idorsia Pharmaceuticals Japan Ltd and Idorsia Pharmaceuticals Korea Co., Ltd in 2023. QUVIVIQ was co-developed in Japan by NPJ and Mochida Pharmaceutical Co. Ltd.

About Insomnia Disorder
Insomnia disorder is defined as difficulty initiating or maintaining sleep, causing clinically significant distress or impairment in important areas of daytime functioning. As defined this impact on sleep quantity or quality should be present for at least three nights per week, lasts for at least three months, and occurs despite an adequate opportunity to sleep.

Insomnia is a condition of overactive wake signaling and studies have shown that areas of the brain associated with wakefulness remain more active during sleep in patients with insomnia. According to a survey by Japan’s Ministry of Health, Labour and Welfare in 2018, about 20% of Japanese adults struggle to get enough rest from sleep.

Insomnia as a disorder is quite different from a brief period of poor sleep, and it can take its toll on both physical and mental health. It is a persistent condition with a negative impact on daytime functioning. Research has shown that poor quality sleep can affect many aspects of daily life, including the ability to concentrate, mood, and energy levels.

The goal of treatments for insomnia is to improve sleep quality and quantity, as well as daytime functioning, while avoiding adverse events and next-morning residual effects. Current recommended treatment of insomnia includes sleep hygiene therapy, cognitive behavioral therapy, and pharmacotherapy.

About the Orexin system
Wake and sleep signaling is regulated by intricate neural circuitry in the brain. One key component of this process is the orexin system, which helps promote wakefulness. There are two forms of orexin neuropeptides – small protein-like molecules used by nerve cells (neurons) to communicate with each other in the brain – orexin A and orexin B. Orexin promotes wakefulness through its receptors OX1R and OX2R. Together, these neuropeptides and receptors make up the orexin system. The orexin system stimulates targeted neurons in the wake system – leading to the release of several chemicals (serotonin, histamine, acetylcholine, norepinephrine) – to promote wakefulness. Under normal circumstances, orexin levels rise throughout the day as wakefulness is promoted and then fall at night. Overactivity of the wake system is an important driver of insomnia.

About the Japanese Phase 3 Study
The Japanese Phase 3 study was a randomized, double-blind, placebo-controlled, parallel-group, multicenter study to investigate the efficacy and safety of daridorexant in patients with insomnia disorder.

The primary objective of the study was to demonstrate the efficacy of 50 mg of daridorexant once daily at bedtime versus placebo for 4 weeks in patients with insomnia disorder. The efficacy of daridorexant was measured by patient reported total sleep time (“sTST”) and latency to sleep onset (“sLSO”).

• The primary efficacy endpoint was change from baseline to Week 4 in sTST and change from baseline to Week 4 in sLSO with 50 mg daridorexant versus placebo.
• The secondary efficacy endpoint was change from baseline to Week 4 in sTST and change from baseline to Week 4 in sLSO with 25 mg daridorexant versus placebo.

The study also evaluated the dose effect of 50 or 25 mg of daridorexant versus placebo using other patient reported sleep measures. The study enrolled 490 patients, randomized 1:1:1 to daridorexant 50 mg, 25 mg or placebo. As insomnia often presents later in life, and older adults are more susceptible to experience fragmented sleep, early awakening, and daytime sleepiness, around 30% of the recruited population was at least 65 years of age.

Key Literature

• Riemann, D., et al. Sleep. 2017;26(6):675-700.
• The Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM–5; American Psychiatric Association, 2013).
• Wardle-Pinkston S., et al. Sleep Med Rev. 2019;48.
• Mignot, E., et al. Lancet Neurol. 2022;21:125–39.
• Muehlan, C., et al. Expert Opin. Drug Metab. Toxicol. 2020;16(11):1063–1078.
• Muehlan, C., et al. J Psychopharmacol. 2020;34(3):326-335.
• Buysse, D.J., et al. Drug Discov Today Dis Models. 2011;8(4):129-137.
• Levenson, J.C., et al. Chest. 2015;147(4):1179-1192.
• Boof, M.L., et al. Eur J Clin Pharmacol. 2019;75(2):195-205.
• Clifford, B.S., et al. Trends Neurosci. 2001;24(12).726-31.
• Gotter, A.L., et al. BMC Neuroscience. 2013;14(1):14-19.
• Patel, D., et al. J Clin Sleep Med. 2018;14(06):1017–1024.
• Fietze I., et al. Drugs Aging. 2022 Oct;39(10):795-810.
• Kunz D, et al. CNS Drugs. 2022 Dec 9.

About Makoto Uchiyama, M.D., Ph.D.
Director, Tokyo Adachi Hospital, Tokyo
Lecturer, Departments of Psychiatry and Sleep Medicine, Nihon University School of Medicine, Tokyo
Visiting Professor, Department of Psychiatry, Toho University School of Medicine, Tokyo
Educational Achievements and certificates:
M.D., Tohoku University, School of Medicine, Sendai, 1980
Ph.D., Tokyo Medical and Dental University, Tokyo, 1994
Designated Physician of Mental Health, Ministry of Health, Labor and Welfare, 1987
Board Certified Physician of the Japanese Society of Sleep Research, 2002
Certified Psychiatrist of the Japanese Board of Psychiatry, 2006
Board-certified Clinical Neurophysiologist (EEG section), Japanese Society of Clinical Neurophysiology, 2006

Dr Uchiyama serves as a consultant to Nxera Pharma Japan Co., Ltd.

About Nxera Pharma
Nxera Pharma (formerly Sosei Heptares) is a technology powered biopharma company, in pursuit of new specialty medicines to improve the lives of patients with unmet needs in Japan and globally.

In addition to several products being commercialized in Japan, we are advancing an extensive pipeline of over 30 active programs from discovery through to late clinical stage internally and in partnership with leading pharma and biotech companies. This pipeline is focused on addressing major unmet needs in some of the fastest-growing areas of medicine across neurology, GI and immunology, metabolic disorders and rare diseases, and leverages the power of our unique and industry leading GPCR-targeted structure-based drug discovery NxWave^TM platform to provide a sustainable source of best- or first-in-class candidates.

Nxera employs over 350 talented people at key locations in Tokyo and Osaka (Japan), London and Cambridge (UK), Basel (Switzerland) and Seoul (South Korea) and is listed on the Tokyo Stock Exchange (ticker: 4565).

For more information, please visit www.nxera.life
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