DOCSLIB.ORG

Idorsia Adds Insomnia to Its Pipeline Successes

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Idorsia Adds Insomnia to Its Pipeline Successes April 20, 2020 Idorsia adds insomnia to its pipeline successes Jacob Plieth Daridorexant scores in the first of two phase III insomnia studies, but attention will fall on a secondary endpoint measuring daytime performance. When Idorsia was created in the wake of Johnson & Johnson’s takeover of Actelion, and then licensed its lead to J&J, its fate looked to be sealed. But instead of also being taken over Idorsia has set about developing its own pipeline, and today reported a positive pivotal study hit with daridorexant, a separate lead asset. Daridorexant, a dual orexin receptor antagonist in development for insomnia, looks to have aced all four primary endpoints in the first of its two phase III trials, at both doses tested. While the data have yet to be scrutinised in detail, what looks to be an absence of sleep-inducing drugs’ typical side effects could give Idorsia’s immunology/cardiology pipeline an added focus. However, analysts will likely zero in on one key secondary endpoint, namely patients’ daytime performance. This was measured using IDSIQ, a patient-reported questionnaire developed by Idorsia and validated by the US FDA. According to this metric daridorexant 50mg, but not 25mg, hit statistical significance versus placebo. This is important because Idorsia’s second pivotal trial tests 10mg and 25mg, so if this result is consistent the company might see no benefit on daytime performance in the second study. Nevertheless, on an analyst call today executives said the trial that just read out marked the first time an insomnia product had improved performance during the day in addition to improving sleep quality at night. Daridorexant enables patients to “sleep faster, sleep longer and function better the next day”, said Idorsia’s chief executive, Jean-Paul Clozel. Whether a single trial backing just one dose of a product is sufficient to make such a claim will remain a key focus as the markets await full data and readout of the second pivotal study, due later this year. As for the primary endpoints, there seems little doubt about daridorexant’s efficacy. Both doses beat placebo in one and three-month sleep maintenance and sleep onset. WASO = wake after sleep onset (measure of sleep maintenance); LPS = latency to persistent sleep (sleep onset); sTST = subjective total sleep time; IDSIQ = insomnia daytime symptoms and impacts questionnaire. Source: Idorsia presentation. Perhaps even more importantly, adverse events looked balanced across the three cohorts; numerically there were more falls and fainting with placebo than active drug, and none of the adverse events listed were more prevalent with 50mg than with 25mg. Safety is a vital consideration for insomnia drugs, because of their propensity to cause sleepiness during the day. Two other orexin receptor antagonists are approved – Merck & Co’s Belsomra and Eisai’s Dayvigo – but both carry warnings of daytime impairment and possible effects on driving performance. With Idorsia trading up 16% today, clearly the hope is that daridorexant could revolutionise insomnia treatment; sellside forecasts see 2024 revenue of $190m at present, according to EvaluatePharma, so an upgrade looks likely should the full data retain their lustre. Daridorexant’s development also owes much to persistence in R&D; when Mr Clozel was running Actelion that company had been developing an earlier version of the orexin approach, almorexant, but this project was pulled because of drug-drug interactions (Actelion re-awakens research on sleep medicine, July 7, 2016). Today’s daridorexant data back the decision to press on. Three years after Mr Clozel got J&J to pay $30bn for Actelion and $230m for an Idorsia asset, the Midas touch has not deserted him. Daridorexant's pivotal programme Study Design Data 25mg & 50mg vs All primary endpoints met; secondary performance endpoint (IDSIQ) NCT03545191 placebo stat sig only for 50mg 10mg & 25mg vs NCT03575104 Study ends Apr 2020 placebo More from Evaluate Vantage Evaluate HQ 44-(0)20-7377-0800 Evaluate Americas +1-617-573-9450 Evaluate APAC +81-(0)80-1164-4754 © Copyright 2021 Evaluate Ltd..
Load more

Recommended publications
  • The Pharmacoeconomic Burden of Insomnia
    The Pharmacoeconomic Burden of Insomnia: Current Treatment Challenges and an Update on Safe and Efficacious Options © 2020. All rights reserved. No part of this report may be reproduced or distributed without the expressed written permission of PTCE. Faculty Information Julie A. Dopheide, PharmD, BCPP, FASHP Douglas S. Burgoyne, PharmD, FAMCP Professor of Clinical Pharmacy, Adjunct Associate Professor Psychiatry and the Behavioral Sciences Department of Pharmacotherapy University of Southern California School University of Utah College of Pharmacy of Pharmacy and Keck School of Medicine Salt Lake City, Utah Los Angeles, California This activity is supported by an educational grant from Eisai. Educational Objectives After completion of this activity, participants will be able to: • Characterize the pathophysiology, epidemiology, and disease burden of insomnia including the impact on quality of life in vulnerable patient groups • Identify appropriate pharmacotherapy for insomnia based on guideline recommendations, drug efficacy and safety profiles, and patient factors • Examine the economic burden of insomnia and impact of available treatment options, including effects on vulnerable patient groups Insomnia Overview Julie Dopheide, PharmD, BCPP, FASHP Emily Morris, 16 years old Emily Morris, 16 years old 2020 National Sleep Foundation Poll Shows High Levels of Daytime Sleepiness and Negative Health Impact #1 Cause of Daytime Sleepiness: Insomnia Health Impacts of Feeling Sleepy Feeling Sleepy How Many Days Per Week? 5-7 days 28% 28% 2-4 days 44% 0-1 days 0 20 40 60 1-2 days 2-4 days 5-7 days Feeling Unwell Headache Irritability Sleep in America Poll 2020. National Sleep Foundation. Published March 2020. Accessed October 8, 2020.
    [Show full text]
  • Clinical Pharmacology of Daridorexant, a Novel Dual Orexin Receptor Antagonist
    Clinical pharmacology of daridorexant, a novel dual orexin receptor antagonist Inauguraldissertation zur Erlangung der Würde eines Dr. sc. med. Vorgelegt der Medizinischen Fakultät der Universität Basel Von Clemens Mühlan aus 4055 Basel, Schweiz Basel, 2021 Originaldokument gespeichert auf dem Dokumentenserver der Universität Basel edoc.unibas.ch Genehmigt von der Medizinischen Fakultät auf Antrag von Prof. Dr. Stephan Krähenbühl Prof. Dr. Matthias Liechti Dr. Alexander Jetter Dr. Jasper Dingemanse Basel, 24. Februar 2021 Dekan Prof. Dr. Primo Leo Schär 2 of 118 TABLE OF CONTENTS LIST OF ABBREVIATIONS AND ACRONYMS ............................................................4 ACKNOWLEDGEMENTS .................................................................................................8 SUMMARY .........................................................................................................................9 1 BACKGROUND AND INTRODUCTION ................................................................15 1.1 Insomnia .......................................................................................................15 1.2 The orexin system as a therapeutic target .....................................................18 1.3 Review of orexin receptor antagonists .........................................................20 1.4 Selective vs dual orexin receptor antagonism ..............................................23 1.5 Orexin receptor antagonists available in clinical practice ............................24 1.6 Orexin receptor
    [Show full text]
  • Rxoutlook® 4Th Quarter 2020
    ® RxOutlook 4th Quarter 2020 optum.com/optumrx a RxOutlook 4th Quarter 2020 While COVID-19 vaccines draw most attention, multiple “firsts” are expected from the pipeline in 1Q:2021 Great attention is being given to pipeline drugs that are being rapidly developed for the treatment or prevention of SARS- CoV-19 (COVID-19) infection, particularly two vaccines that are likely to receive emergency use authorization (EUA) from the Food and Drug Administration (FDA) in the near future. Earlier this year, FDA issued a Guidance for Industry that indicated the FDA expected any vaccine for COVID-19 to have at least 50% efficacy in preventing COVID-19. In November, two manufacturers, Pfizer and Moderna, released top-line results from interim analyses of their investigational COVID-19 vaccines. Pfizer stated their vaccine, BNT162b2 had demonstrated > 90% efficacy. Several days later, Moderna stated their vaccine, mRNA-1273, had demonstrated 94% efficacy. Many unknowns still exist, such as the durability of response, vaccine performance in vulnerable sub-populations, safety, and tolerability in the short and long term. Considering the first U.S. case of COVID-19 was detected less than 12 months ago, the fact that two vaccines have far exceeded the FDA’s guidance and are poised to earn EUA clearance, is remarkable. If the final data indicates a positive risk vs. benefit profile and supports final FDA clearance, there may be lessons from this accelerated development timeline that could be applied to the larger drug development pipeline in the future. Meanwhile, drug development in other areas continues. In this edition of RxOutlook, we highlight 12 key pipeline drugs with potential to launch by the end of the first quarter of 2021.
    [Show full text]
  • ACNP 59Th Annual Meeting: Poster Session I
    www.nature.com/npp ABSTRACTS COLLECTION ACNP 59th Annual Meeting: Poster Session I Neuropsychopharmacology (2020) 45:68–169; https://doi.org/10.1038/s41386-020-00890-7 Sponsorship Statement: Publication of this supplement is sponsored by the ACNP. Presenting author disclosures may be found within the abstracts. Asterisks in the author lists indicate presenter of the abstract at the annual meeting. M1. Juvenile Social Isolation of Rats Induces Lost of Jessica Jessica Deslauriers*, Jose Figueroa, Cindy Napan, Corticotropin Releasing Factor-Receptor 1 Antagonist Effect in Yanilka Soto-Muniz, Victoria Risbrough the Nucleus Accumbens Université Laval, Québec, Canada Katia Gysling*, Juan Zegers, Javier Novoa, Hector Yarur Background: Post-traumatic stress disorder (PTSD) is a common Pontificia Universidad Catolica de Chile, Santiago, Chile psychiatric condition that is defined by its paradigmatic symptoms including but not limited to anxiety, avoidance, and increased arousal Background: Social isolation is a model of chronic stress widely by environmental cues due to a severely traumatic event. Recent used to study early life adversity. It is well known that early life studies show that this condition is correlated with both peripheral 1234567890();,: adversity may lead to the development of psychiatric disorders in and central immune dysfunction, but the relationship between adulthood. Juvenile rats exposed to social isolation showed inflammation and PTSD remains unclear. In a mouse model of PTSD, increased anxiety-like behavior and significant changes in Nucleus we found increased plasma levels of the pro-inflammatory cytokine Accumbens (Nac) dopamine (DA) activity in adulthood (Lukkes interleukin-1β (IL-1β) after exposure to trauma. A major component in et al.
    [Show full text]
  • Minutes of the CHMP Meeting 22-25 March 2021
    17 May 2021 EMA/CHMP/258452/2021 Human Medicines Division Committee for medicinal products for human use (CHMP) Minutes for the meeting on 22-25 March 2021 Chair: Harald Enzmann – Vice-Chair: Bruno Sepodes Disclaimers Some of the information contained in this set of minutes is considered commercially confidential or sensitive and therefore not disclosed. With regard to intended therapeutic indications or procedure scopes listed against products, it must be noted that these may not reflect the full wording proposed by applicants and may also vary during the course of the review. Additional details on some of these procedures will be published in the CHMP meeting highlights once the procedures are finalised and start of referrals will also be available. Of note, these minutes are a working document primarily designed for CHMP members and the work the Committee undertakes. Note on access to documents Some documents mentioned in the minutes cannot be released at present following a request for access to documents within the framework of Regulation (EC) No 1049/2001 as they are subject to on- going procedures for which a final decision has not yet been adopted. They will become public when adopted or considered public according to the principles stated in the Agency policy on access to documents (EMA/127362/2006). Official address Domenico Scarlattilaan 6 ● 1083 HS Amsterdam ● The Netherlands Address for visits and deliveries Refer to www.ema.europa.eu/how-to-find-us Send us a question Go to www.ema.europa.eu/contact Telephone +31 (0)88 781 6000 An agency of the European Union © European Medicines Agency, 2021.
    [Show full text]
  • A New Medication for Insomnia in Older Adults?
    PATIENT PAGE Daridorexant: A new medication for insomnia in older adults? Jennifer Rose V. Molano, MD First published February 24, 2020, DOI: http://dx.doi.org/10.1212/WNL.0000000000009489 Related Articles Daridorexant, a new dual orexin receptor antagonist, in elderly subjects with insomnia disorder http://dx.doi.org/10.1212/ WNL.0000000000009489 What was the study and why is it important? In this issue of Neurology®, the authors of this study determined whether daridorexant, a new sleep medication, was safe and effective in treating insomnia for adults >65 years of age.1 Insomnia is difficulty falling asleep or staying asleep that may interfere with daytime functioning, including an increased risk for falls, mood disorders such as depression, and decreased quality of life.2,3 It can be seen in about half of older adults. There are treatments, but commonly used medications for insomnia in older adults can increase the risk of thinking problems and falls.2,3 How was the study done? In this study, participants reported that they usually took >30 minutes to fall asleep, woke up for >30 minutes after falling asleep, and had a total sleep time of <6 1/2 hours at least 3 times a week over 3 months. People could not join the study if they had known conditions that interfered with sleep. These included obstructive sleep apnea, restless legs syndrome, too much caffeine use, daytime naps >1 hour, and jet lag, among others. The researchers studied 58 people who fit these rules. About two-thirds were women. First, they collected information about their usual sleep.
    [Show full text]
  • International Nonproprietary Names for Pharmaceutical Substances (INN)
    WHO Drug Information, Vol. 32, No. 4, 2018 Proposed INN: List 120 International Nonproprietary Names for Pharmaceutical Substances (INN) Notice is hereby given that, in accordance with article 3 of the Procedure for the Selection of Recommended International Nonproprietary Names for Pharmaceutical Substances, the names given in the list on the following pages are under consideration by the World Health Organization as Proposed International Nonproprietary Names. The inclusion of a name in the lists of Proposed International Nonproprietary Names does not imply any recommendation of the use of the substance in medicine or pharmacy. Lists of Proposed (1–117) and Recommended (1–78) International Nonproprietary Names can be found in Cumulative List No. 17, 2017 (available in CD-ROM only). The statements indicating action and use are based largely on information supplied by the manufacturer. This information is merely meant to provide an indication of the potential use of new substances at the time they are accorded Proposed International Nonproprietary Names. WHO is not in a position either to uphold these statements or to comment on the efficacy of the action claimed. Because of their provisional nature, these descriptors will neither be revised nor included in the Cumulative Lists of INNs. Dénominations communes internationales des Substances pharmaceutiques (DCI) Il est notifié que, conformément aux dispositions de l'article 3 de la Procédure à suivre en vue du choix de Dénominations communes internationales recommandées pour les Substances pharmaceutiques les dénominations ci-dessous sont mises à l'étude par l'Organisation mondiale de la Santé en tant que dénominations communes internationales proposées.
    [Show full text]
  • ACNP 59Th Annual Meeting: Poster Session III
    www.nature.com/npp ABSTRACTS COLLECTION ACNP 59th Annual Meeting: Poster Session III Neuropsychopharmacology (2020) 45:278–382; https://doi.org/10.1038/s41386-020-00892-5 Sponsorship Statement: Publication of this supplement is sponsored by the ACNP. Presenting author disclosures may be found within the abstracts. Asterisks in the author lists indicate presenter of the abstract at the annual meeting. W1. Efforts to Develop and Validate Models and Endpoints understanding these endpoints and representative data will be Within the NINDS Preclinical Screening Platform for Pain presented. (PSPP) Conclusions: This presentation will describe efforts to standar- dize models and endpoints to enhance rigor and reproducibility Taleen Hanania, Mark Varney, Emer Leahy, David Budac, while evaluating potential non-opioid, non-addictive therapeutics Elizabeth Dugan, Steven Leiser, Mark Urban, Sarah Woller, for pain within the NINDS HEAL Initiative PSPP program. Smriti Iyengar* Keywords: Pain, Preclinical Models and Endpoints, Validation, Heal Initiative NINDS/NIH, Carmel, Indiana, United States Disclosure: Electrical Engineering, Delphi: Employee (Spouse), Eli Lilly: Retiree, Stock / Equity (Self) 1234567890();,: Background: The NIH Helping to End Addiction Long-term Initiative, or NIH HEAL Initiative, is a trans-agency effort to W2. The D1 Positive Allosteric Modulator, DETQ, Improves provide scientific solutions to the opioid crisis. As part of the NIH Cognition in Aged Mice and Enhance Cortical and HEAL Initiative, the National Institute of Neurological Disorders Hippocampal Acetylcholine Efflux and Stroke (NINDS) has been charged with enhancing pain management and accelerating the discovery and development Herbert Meltzer*, Lakshmi Rajagopal, Mei Huang, Kjell of new non-addictive pain therapeutics. Toward this goal, NINDS Svensson created the Preclinical Screening Platform for Pain (PSPP) with the aim of accelerating the preclinical development of non- Northwestern University, Chicago, Illinois, United States opioid, non-addictive therapeutics for pain.
    [Show full text]
  • A New Dual Orexin Receptor Antagonist for the Treatment of Insomnia
    Psychopharmacology (2021) 238:2693–2708 https://doi.org/10.1007/s00213-021-05954-0 REVIEW Nonclinical pharmacology of daridorexant: a new dual orexin receptor antagonist for the treatment of insomnia Catherine Roch1 · Giorgio Bergamini1 · Michel A. Steiner1 · Martine Clozel1 Received: 4 May 2021 / Accepted: 3 August 2021 / Published online: 20 August 2021 © The Author(s) 2021 Abstract Dual orexin receptor antagonists (DORAs) represent a novel type of sleep medication that provide an alternative to the tra- ditionally used positive allosteric gamma-aminobutyric acid (GABA)-A receptor modulators. Daridorexant is a new DORA that exhibited in phase 3 trials in insomnia not only a benefcial efect on sleep variables, measured objectively and assessed subjectively, but also an improvement in daytime functioning. Daridorexant was discovered through a tailored research pro- gram aimed at identifying an optimized sleep-promoting molecule with pharmacokinetic properties appropriate for covering the whole night while avoiding next-morning residual activity at efcacious doses. By specifc binding to both orexin recep- tors, daridorexant inhibits the actions of the wake-promoting orexin (also called hypocretin) neuropeptides. This mechanism avoids a more widespread inhibition of neuronal pathways and associated side efects that are intrinsic to positive allosteric GABA-A receptor modulators. Here, we review the general pharmacology of daridorexant, based on nonclinical pharmacol- ogy studies of daridorexant, unpublished or already described, or based on work with other DORAs. Some unique features of daridorexant will be highlighted, such as the promotion of natural and surmountable sleep, the preservation of memory and cognition, the absence of tolerance development or risk of physical dependence, and how it can beneft daytime functioning.
    [Show full text]
  • Orexins/Hypocretins and Cancer: a Neuropeptide As Emerging Target
    molecules Review Orexins/Hypocretins and Cancer: A Neuropeptide as Emerging Target Couvineau Alain * , Nicole Pascal, Gratio Valérie and Voisin Thierry INSERM UMR1149/Inflammation Research Center (CRI), Team “From Inflammation to Cancer in Digestive Diseases” Labeled by “la Ligue Nationale Contre le Cancer”, University of Paris, DHU UNITY, 75018 Paris, France; [email protected] (N.P.); [email protected] (G.V.); [email protected] (V.T.) * Correspondence: [email protected] Abstract: Over 20 years ago, orexin neuropeptides (Orexin-A/hypocretin-1 and Orexin-B/hypocretins-2) produced from the same precursor in hypothalamus were identified. These two neurotransmitters and their receptors (OX1R and OX1R), present in the central and peripheral nervous system, play a major role in wakefulness but also in drug addiction, food consumption, homeostasis, hormone secretion, reproductive function, lipolysis and blood pressure regulation. With respect to these biological functions, orexins were involved in various pathologies encompassing narcolepsy, neurodegenerative diseases, chronic inflammations, metabolic syndrome and cancers. The expression of OX1R in various cancers including colon, pancreas and prostate cancers associated with its ability to induce a proapoptotic activity in tumor cells, suggested that the orexins/OX1R system could have a promising therapeutic role. The present review summarizes the relationship between cancers and orexins/OX1R system as an emerging target. Keywords: orexins; neuropeptide; GPCR; apoptosis; cancer; gastroenterology Citation: Alain, C.; Pascal, N.; Valérie, G.; Thierry, V. Orexins/ Hypocretins and Cancer: A Neuropeptide as Emerging Target. 1. Introduction Molecules 2021, 26, 4849. https:// The identification of orexin, also termed hypocretin, is still young in science history [1]. doi.org/10.3390/molecules26164849 It was in the late 1990s, when two independent groups identified and characterized these neuropeptides in mouse hypothalamus [2,3].
    [Show full text]
  • 20 Years of Medicinal Chemistry ÂŒ Always Look at the Bright Side
    SCS LaureateS and awardS & FaLL Meeting 2020 CHIMIA 2020, 74, No. 7/8 549 doi:10.2533/chimia.2020.549 Chimia 74 (2020) 549–560 © C. Boss 20 Years of Medicinal Chemistry – Always Look at the Bright Side (of Life) Christoph Boss* SCS Industrial Science Award 2019 Abstract: This paper summarizes a personal perspective on key learnings from projects the author was involved in over the last 20 years. For example, the discovery of macitentan, the most successful molecule to date from this personal collection, marketed by J&J for the treatment of pulmonary arterial hypertension (PAH).[1] Then the discovery of ACT-462206, a dual orexin receptor antagonist for the treatment of insomnia disorder with a serendipitously short story from the screening hit to the drug[2] followed by the identification of daridorexant, another dual orexin receptor antagonist. Daridorexant successfully passed first pivotal phase 3 clinical trial in April 2020 for the treatment of insomnia disorder[3] (“Good things come to those who wait”). Finally, ACT-451840, an antimalarial drug with a novel mechanism of action, identified in the perfect collaboration between academia and industry. The compound is in phase 2 clinical development.[4] In addition, the importance of the screening compound collection is briefly discussed, as a key asset for drug discovery. The measures Idorsia implemented to obtain valuable hits from high-throughput screening (HTS) campaigns are elaborated.[5] Drug discovery is a multi-disciplinary business with unlimited exciting challenges asking for excessive optimism when tackling them in a playful manner. Keywords: Endothelin receptor antagonist · G-protein-coupled receptor (GPCR) · Insomnia disorder · Malaria · Medicinal chemistry · Orexin receptor antagonist · Screening compound collection Christoph Boss studied chemistry at the ment of insomnia disorder in April 2020.
    [Show full text]
  • Reaching out for More
    Idorsia – Reaching out for more The following 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. 2 J.P. Morgan Healthcare Conference | 12 Jan 2021 “We have one simple vision: creating a sustainable mid-size pharma company based on innovation” Jean-Paul Clozel Chief Executive Officer 3 J.P. Morgan Healthcare Conference | 12 Jan 2021 The origin of Idorsia 4 J.P. Morgan Healthcare Conference | 12 Jan 2021 USD 30 Billion acquisition of Actelion – Idorsia is born Marketed products – PAH franchise, late-stage pipeline with royalties to Idorsia, option to license aprocitentan All research projects and early-stage pipeline 5 J.P.
    [Show full text]