
Daridorexant Phase 3 results in insomnia presented at SLEEP 2020
Allschwil, Switzerland – August 28, 2020
Idorsia Ltd (SIX: IDIA) today announced that the positive results from the first pivotal Phase 3 study (evaluating 25 and 50 mg doses) of its investigational dual orexin receptor antagonist, daridorexant, in adult and elderly patients with insomnia, were presented by Dr Thomas Roth at SLEEP 2020. The study demonstrated efficacy of treatment with daridorexant on objective and subjective sleep parameters, and daytime functioning, with no next-morning residual effect.
The Associated Professional Sleep Societies (APSS) event, SLEEP 2020, is the world’s largest meeting devoted entirely to clinical sleep medicine, and sleep and circadian research and is currently taking place as a virtual meeting. The presentation, entitled “Efficacy and safety of daridorexant in adult and elderly patients with insomnia”, is available for on-demand replay for registered participants through August 1, 2021.
Dr Thomas Roth, PhD, Director of the Sleep Disorder and Research Center at Henry Ford Hospital, commented:
“Daridorexant, a new dual orexin receptor antagonist, has a pharmacokinetic and pharmacodynamic profile optimized for sleep onset and duration of action to improve night-time efficacy, without residual effects. These pharmacological properties led us to hypothesize that daridorexant could also improve the impaired daytime functioning frequently observed in insomnia. A new patient-reported outcome instrument was developed – and validated according to FDA requirements – to specifically assess daytime functioning in patients with insomnia and we included it in the Phase 3 program. The results have been outstanding.”
The Phase 3 trial was designed to measure the impact of daridorexant on objective and subjective sleep parameters as well as on daytime functioning, and to evaluate safety, in patients with moderate to severe insomnia. Sleep variables were assessed using polysomnography for wake after sleep onset (WASO) and latency to persistent sleep (LPS). A sleep diary questionnaire was used to measure subjective total sleep time (sTST). Daytime functioning was assessed using a newly developed and validated patient-reported outcome instrument, the Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ). The IDSIQ comprises 14 items grouped into three domains that reflect daytime effects of insomnia that are commonly encountered in clinical practice: Alert/Cognition, Mood, and Sleepiness/Tiredness.
Daridorexant significantly improved sleep maintenance as measured by a larger decrease in WASO from baseline compared to placebo. The mean change from baseline in WASO (minutes) for placebo, 25 mg and 50 mg was -6.2, -18.4, and -29.0 at 1 Month and -11.1, -23.0 and -29.4 at 3 Months, respectively (all p values vs. placebo <0.0001).
Daridorexant significantly improved sleep onset as measured by a larger decrease in LPS from baseline compared to placebo. The mean change from baseline in LPS (minutes) for placebo, 25mg and 50mg was -19.9, -28.2 (p=0.0005) and -31.2 (p<0.0001) at 1 Month and, -23.1, -30.7 (p=0.0015) and -34.8 (p<0.0001) at 3 Months, respectively (p-values vs placebo).
Subjective total sleep time assessed daily by patients increased more with daridorexant from baseline compared to placebo. The mean change from baseline in sTST (minutes) for placebo, 25mg and 50mg was 21.6, 34.2 (p=0.0013), and 43.6 (p<0.0001) at 1 Month, and 37.9, 47.8 (p=0.0334), 57.7 (p<0.0001) at 3 Months, respectively (p-values vs placebo).
Daridorexant improved daytime functioning, as measured in a secondary efficacy endpoint by the Sleepiness/Tiredness domain of the IDSIQ. For this domain, the improved daytime functioning was demonstrated by a mean score reduction from baseline for placebo, 25mg and 50mg of -2.0,
-2.8 (p=0.0547) and -3.8 (p<0.0001) at 1 Month, and of -3.8, -4.8 (p=0.0534) and -5.7 (p=0.0002) at
3 Months, respectively (p-values vs placebo). In addition, other efficacy endpoints from the IDSIQ patient-reported outcome instrument, namely the “Alert/Cognition” domain, “Mood” domain, and the “Total IDSIQ” scores, consistently showed a dose-dependent improvement, as presented.
The most frequent AEs, nasopharyngitis and headache, were balanced between arms. Somnolence was reported in 6 (1.9%) patients on placebo, 11 (3.5%) patients on daridorexant 25mg, and 5 (1.6%) of patients on daridorexant 50mg.
The late breaking abstract (LBA 4) is available in the Virtual Sleep 2020 meeting guide.
Dr Roth concluded:
“As hypothesized, the optimized profile of daridorexant not only translated in this study into a dose-dependent improvement on objective and subjective sleep parameters, but also into improved daytime functioning, all of which was sustained over time. Very importantly, safety was comparable with daridorexant 25 mg and 50 mg, with no dose-limiting safety findings, no observed next-morning sleepiness compared to placebo, no signals suggestive of rebound insomnia compared to baseline sleep parameters, and no withdrawal effects. With these results daridorexant addresses important needs of patients with insomnia.”
The Phase 3 program design was also presented as a poster entitled “Daridorexant (ACT-541468), a dual orexin receptor antagonist, for the treatment of insomnia disorder: Phase 3 program for assessing efficacy and safety in adult and elderly patients”. The poster is available on demand to registered attendees of SLEEP 2020 and the abstract can be found in the Abstract Supplement.
In April and July 2020, Idorsia reported positive results in each of the two pivotal Phase 3 studies of daridorexant in patients with insomnia. More details and commentary can be found in the dedicated press releases (first study release), (second study release) and the investor webcasts (first study webcast), (second study webcast) which are available for replay on the corporate website.
Notes to the editor
About daridorexant
Daridorexant is a potent, selective, dual orexin receptor antagonist (DORA) currently in development for the treatment of insomnia. Orexin neurons are localized in the lateral hypothalamus and function as a key regulator of wakefulness, signaling other wake promoting neurons to be active, thus maintaining a "wake state". Insomnia is a condition of overactive wake signaling. Studies have shown that areas of the brain associated with wakefulness remain more active during sleep in patients with insomnia. Blocking the activity of orexin reduces the downstream activity of other wake promoting neurotransmitters, allowing sleep to occur. Daridorexant has a pharmacokinetic and pharmacodynamic profile that was tailored specifically for the treatment of insomnia, including fast absorption to support sleep onset, a half-life designed to promote sleep maintenance throughout the night and minimize the risk of relevant carry-over exposure in the morning, without accumulation over time. Daridorexant has shown clinical efficacy in Phase 2 and 3 clinical studies and is expected to be submitted for regulatory review around the end of 2020.
About the Phase 3 registration program
The Phase 3 registration program comprises two confirmatory studies of 3-month duration, together with a long-term extension study. Both pivotal studies are complete, having enrolled around 1,850 patients with insomnia at over 160 sites across 18 countries. As insomnia often presents later in life, around 40% of the recruited population was aged 65 years or older. The confirmatory multi-center, double-blind, randomized, placebo-controlled, parallel-group, polysomnography studies investigated three doses of daridorexant (10 mg, 25 mg, and 50 mg) on sleep and daytime functioning parameters, objectively in a sleep lab by polysomnography and subjectively with a daily patient diary at home.
The impact of insomnia on patients’ daytime functioning was measured daily using the sleepiness domain score from the Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ) a Patient Reported Outcome (PRO) instrument, validated according to the US Food and Drug Administration (FDA) Guidance for Industry. 806 patients decided to continue treatment in the ongoing 40-week extension study which will measure the effect of all three doses vs. placebo, generating data for long-term treatment of insomnia.
About insomnia
Insomnia is defined as a combination of dissatisfaction with sleep and a significant negative impact on daytime functioning. Dissatisfaction with sleep refers to the difficulty to initiate and/or maintain sleep on at least three nights per week for at least three months, despite adequate opportunity to sleep.
Insomnia is, worldwide, the most commonly reported sleep disorder and its impact is often underestimated. It can be a distressing condition that can impair quality of life. Sleepless nights can leave people feeling irritable and out of sorts – this may affect many aspects of daily life, from studying and employment to social activities and relationships. People who suffer from insomnia may lack the energy or motivation to exercise or to take part in social activities. It can also have a significant economic impact as it increases the risk of accident and injury on the road or in the workplace and is a leading cause of absenteeism and reduced productivity at work. People with insomnia are more likely to experience feeling down or depressed, lack concentration, and suffer from poor energy levels during the day compared with people who sleep well. In addition, worrying about sleep can cause stress and may lead to negative thought patterns which may in turn make it more difficult to sleep, setting up a vicious cycle. Chronic insomnia is associated with cardiovascular and cerebrovascular diseases, and increased mortality.
The goal of treatment for insomnia is to improve sleep quality and quantity, as well as to reduce insomnia-related impaired daytime functioning, while avoiding adverse events and next morning residual effects. Current treatment of insomnia includes cognitive behavioral therapy, sleep hygiene recommendations, and pharmacotherapy. The most widely prescribed products on the market that are indicated for insomnia enhance the effects of gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. Such medications are only approved for short-term use and are associated with side effects such as next-day effects, anterograde amnesia, and risk of tolerance and dependence.
About Dr. Thomas Roth, PhD
Dr. Roth has been the Director of the Sleep Disorders and Research Center at Henry Ford Hospital in Detroit, since 1978. Dr. Roth is also a Professor in the Department of Psychiatry at Wayne State University, School of Medicine in Detroit, Michigan, and serves as a Clinical Professor in the Department of Psychiatry at the University of Michigan, College of Medicine in Ann Arbor.
After serving as president of the Sleep Research Society, and the founding president of the National Sleep Foundation (NSF), Dr. Roth became chairman of the National Center on Sleep Disorders Research advisory board. In addition, he was a member of the board of directors of the Associated Professional Sleep Societies (APSS), chaired the Association's Scientific Program Committee and the governing board of the World Federation of Sleep Research Societies.
Dr. Roth was instrumental in the formation of the Association of Sleep Disorders Center (ASDC) and served as the organization's second president. He is also the former Chairman of the World Health Organization's worldwide project on sleep and health. In addition to authoring and co-authoring numerous articles, Dr. Roth serves as past editor-in-chief of the journal Sleep. He currently sits on the editorial boards of Sleep Reviews, Stress Medicine, and Advances in Therapy and Human Psychopharmacology.
In 2002, Dr. Roth received the NSF's Lifetime Achievement Award for his accomplishments and contributions to sleep science, sleep medicine and public health. He received a Distinguished Research Award from the Sleep Research Society as well as the Nathanial Kleitman Award from the Academy of Sleep Medicine. Dr. Roth's contributions to the sleep field are expansive, ranging from prolific research productivity and scholarship to multiple national leadership positions, as well as the mentoring of many students and colleagues. Dr. Roth serves as a consultant to Idorsia.
About Idorsia
Idorsia Ltd is reaching out for more - We have more ideas, we see more opportunities and we want to help more patients. In order to achieve this, we will develop Idorsia into one of Europe’s leading biopharmaceutical companies, with a strong scientific core.
Headquartered in Switzerland - a biotech-hub of Europe - Idorsia is specialized in the discovery and development of small molecules, to transform the horizon of therapeutic options. Idorsia has a broad portfolio of innovative drugs in the pipeline, an experienced team, a fully-functional research center, and a strong balance sheet – the ideal constellation to bringing R&D efforts to business success.
Idorsia was listed on the SIX Swiss Exchange (ticker symbol: IDIA) in June 2017 and has over 800 highly qualified specialists dedicated to realizing our ambitious targets.
For further information, please contact
Andrew C. Weiss
Senior Vice President, Head of Investor Relations & Corporate Communications
Idorsia Pharmaceuticals Ltd, Hegenheimermattweg 91, CH-4123 Allschwil
+41 58 844 10 10
www.idorsia.com
The above information contains certain "forward-looking statements", relating to the company's business, which can be identified by the use of forward-looking terminology such as "estimates", "believes", "expects", "may", "are expected to", "will", "will continue", "should", "would be", "seeks", "pending" or "anticipates" or similar expressions, or by discussions of strategy, plans or intentions. Such statements include descriptions of the company's investment and research and development programs and anticipated expenditures in connection therewith, descriptions of new products expected to be introduced by the company and anticipated customer demand for such products and products in the company's existing portfolio. Such statements reflect the current views of the company with respect to future events and are subject to certain risks, uncertainties and assumptions. Many factors could cause the actual results, performance or achievements of the company to be materially different from any future results, performances or achievements that may be expressed or implied by such forward-looking statements. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those described herein as anticipated, believed, estimated or expected.
Attachment
To view this piece of content from www.globenewswire.com, please give your consent at the top of this page.About GlobeNewswire by notified
GlobeNewswire by notified is one of the world's largest newswire distribution networks, specializing in the delivery of corporate press releases financial disclosures and multimedia content to the media, investment community, individual investors and the general public.
Subscribe to releases from GlobeNewswire by notified
Subscribe to all the latest releases from GlobeNewswire by notified by registering your e-mail address below. You can unsubscribe at any time.
Latest releases from GlobeNewswire by notified
Iveco Group signs a 150 million euro term loan facility with Cassa Depositi e Prestiti to support investments in research, development and innovation11.6.2024 12:00:00 CEST | Press release
Turin, 11th June 2024. Iveco Group N.V. (EXM: IVG), a global automotive leader active in the Commercial & Specialty Vehicles, Powertrain and related Financial Services arenas, has successfully signed a term loan facility of 150 million euros with Cassa Depositi e Prestiti (CDP), for the creation of new projects in Italy dedicated to research, development and innovation. In detail, through the resources made available by CDP, Iveco Group will develop innovative technologies and architectures in the field of electric propulsion and further develop solutions for autonomous driving, digitalisation and vehicle connectivity aimed at increasing efficiency, safety, driving comfort and productivity. The financed investments, which will have a 5-year amortising profile, will be made by Iveco Group in Italy by the end of 2025. Iveco Group N.V. (EXM: IVG) is the home of unique people and brands that power your business and mission to advance a more sustainable society. The eight brands are each a
DSV, 1115 - SHARE BUYBACK IN DSV A/S11.6.2024 11:22:17 CEST | Press release
Company Announcement No. 1115 On 24 April 2024, we initiated a share buyback programme, as described in Company Announcement No. 1104. According to the programme, the company will in the period from 24 April 2024 until 23 July 2024 purchase own shares up to a maximum value of DKK 1,000 million, and no more than 1,700,000 shares, corresponding to 0.79% of the share capital at commencement of the programme. The programme has been implemented in accordance with Regulation No. 596/2014 of the European Parliament and Council of 16 April 2014 (“MAR”) (save for the rules on share buyback programmes set out in MAR article 5) and the Commission Delegated Regulation (EU) 2016/1052, also referred to as the Safe Harbour rules. Trading dayNumber of shares bought backAverage transaction priceAmount DKKAccumulated trading for days 1-25478,1001,023.01489,100,86026:3 June 20247,0001,050.597,354,13027:4 June 20245,0001,055.705,278,50028:6 June20243,0001,096.273,288,81029:7 June 20244,0001,106.174,424,68
Landsbankinn hf.: Offering of covered bonds11.6.2024 11:16:36 CEST | Press release
Landsbankinn will offer covered bonds for sale via auction held on Thursday 13 June at 15:00. An inflation-linked series, LBANK CBI 30, will be offered for sale. In connection with the auction, a covered bond exchange offering will take place, where holders of the inflation-linked series LBANK CBI 24 can sell the covered bonds in the series against covered bonds bought in the above-mentioned auction. The clean price of the bonds is predefined at 99,594. Expected settlement date is 20 June 2024. Covered bonds issued by Landsbankinn are rated A+ with stable outlook by S&P Global Ratings. Landsbankinn Capital Markets will manage the auction. For further information, please call +354 410 7330 or email verdbrefamidlun@landsbankinn.is.
Relay42 unlocks customer intelligence with a new insights and reporting module, powered by Amazon QuickSight11.6.2024 11:00:00 CEST | Press release
AMSTERDAM, June 11, 2024 (GLOBE NEWSWIRE) -- Relay42, a leading European Customer Data Platform (CDP), is leveraging Amazon QuickSight to power its new real-time customer intelligence, reporting, and dashboard module. Harnessing the breadth and quality of customer data, the new Insights module empowers marketing teams to dive deep into customer behaviors and gain invaluable insights into the performance of their marketing programs across all online, offline, paid, and owned marketing channels. Preview of the Relay42 Insights module, in pre-beta version Key capabilities of the Relay42 Insights module include: Deep insights into customer behaviors: With the Relay42 Insights module, marketers can ask unlimited questions about their data and gain a deeper understanding of how to serve their customers more effectively. Simplicity with AI-powered querying: Marketers can use artificial intelligence to query their data using natural language search, reducing the reliance on data scientists. Us
Metasphere Labs Announces X Spaces Event on the Topic of Green Bitcoin Mining and Sound Money for Sustainability11.6.2024 10:30:00 CEST | Press release
VANCOUVER, British Columbia, June 11, 2024 (GLOBE NEWSWIRE) -- Metasphere Labs Inc. (formerly Looking Glass Labs Ltd., "Metasphere Labs" or the "Company") (Cboe Canada: LABZ) (OTC: LABZF) (FRA: H1N) is thrilled to announce an engaging Twitter Spaces event on Green Bitcoin mining, energy markets, and sustainability on July 3, 2024 at 2 p.m. ET. Follow us on X at MetasphereLabs for updates and to join the event. What We'll Discuss Bitcoin Mining Basics: Understand the fundamentals of Bitcoin mining.Energy Market Dynamics: Explore how Bitcoin mining interacts with energy markets.Sustainable Innovations: Learn about our efforts to promote sustainability in Bitcoin mining.Sound Money: Discover how tamper-proof currency can enhance stability.Efficient Payment Rails: See how fast, neutral payment systems support humanitarian projects.Carbon Footprint: Compare Bitcoin's environmental impact with traditional banking. "We're excited to host this event and dive into the critical topics of Bitcoin