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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. -
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 -
Orexins, Sleep, and Blood Pressure
Current Hypertension Reports (2018) 20: 79 https://doi.org/10.1007/s11906-018-0879-6 SLEEP AND HYPERTENSION (SJ THOMAS, SECTION EDITOR) Orexins, Sleep, and Blood Pressure Mariusz Sieminski1 & Jacek Szypenbejl1 & Eemil Partinen2,3 Published online: 10 July 2018 # The Author(s) 2018 Abstract Purpose of Review The aim of this review was to summarize collected data on the role of orexin and orexin neurons in the control of sleep and blood pressure. Recent Findings Although orexins (hypocretins) have been known for only 20 years, an impressive amount of data is now available regarding their physiological role. Hypothalamic orexin neurons are responsible for the control of food intake and energy expenditure, motivation, circadian rhythm of sleep and wake, memory, cognitive functions, and the cardiovascular system. Multiple studies show that orexinergic stimulation results in increased blood pressure and heart rate and that this effect may be efficiently attenuated by orexinergic antagonism. Increased activity of orexinergic neurons is also observed in animal models of hypertension. Summary Pharmacological intervention in the orexinergic system is now one of the therapeutic possibilities in insomnia. Although the role of orexin in the control of blood pressure is well described, we are still lacking clinical evidence that this is a possibility for a new approach in the treatment of cardiovascular diseases. Keywords Orexin . Hypocretin . Blood pressure . Sleep . Narcolepsy . Autonomic nervous system Introduction cardiovascular system. With such a variety of functions, orexins appear to be a promising target for therapeutic in- We are celebrating the twentieth anniversary of the discov- terventions aimed at solving the most pivotal health prob- ery of hypocretins/orexins. -
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. -
Royalty Pharma Minerva Press Release January 19 2021
ROYALTY PHARMA ACQUIRES ROYALTY INTEREST IN SELTOREXANT FROM MINERVA NEUROSCIENCES NEW YORK, NY and WALTHAM, MA, January 19, 2021 – Royalty Pharma plc (Nasdaq: RPRX) and Minerva Neurosciences, Inc. (Nasdaq: NERV) today announced that Royalty Pharma will acquire Minerva’s royalty interest in seltorexant for an upfront payment of $60 million and up to $95 million in additional milestone payments. The additional payments to Minerva will be contingent on the achievement of certain clinical, regulatory and commercialization milestones. Seltorexant is currently in Phase 3 development for the treatment of major depressive disorder (MDD) with insomnia symptoms by Janssen Pharmaceutica, N.V., a subsidiary of Johnson & Johnson. “We are very pleased to have entered into this agreement with Royalty Pharma, the leader in acquiring pharmaceutical royalties across the life sciences industry,” said Dr. Remy Luthringer, Executive Chairman and Chief Executive Officer of Minerva. “The proceeds will be used to fund continued development of roluperidone, the Company’s proprietary lead compound, which is in Phase 3 development to treat negative symptoms in schizophrenia.” “We are delighted to partner with Minerva,” said Pablo Legorreta, founder and Chief Executive Officer of Royalty Pharma. “Based on seltorexant’s differentiated mechanism of action and robust clinical evidence to date, we are excited by the therapy’s emerging profile and the opportunity it may bring to address a significant unmet need for the millions of patients with major depressive disorder with insomnia symptoms.” Minerva Neurosciences is entitled to a mid-single digit royalty on worldwide net sales of seltorexant. Cooley acted as legal advisors to Minerva Neurosciences on the transaction. -
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. -
Tackling Insomnia As Part of the Complete Approach to Mental Healthcare
Tackling Insomnia as Part of the Complete Approach to Mental Healthcare Karl Doghramji, MD Professor of Psychiatry, Neurology, and Medicine Medical Director, Jefferson Sleep Disorders Center Thomas Jefferson University Philadelphia, Pennsylvania Educational grant support was provided from Eisai. Faculty Disclosure • Dr. Doghramji: Consultant—Eisai, Purdue, Merck, Pfizer; Stock—Merck. Disclosure • The faculty have been informed of their responsibility to disclose to the audience if they will be discussing off-label or investigational use(s) of drugs, products, and/or devices (any use not approved by the US Food and Drug Administration). – Dr. Doghramji will be discussing off-label use of medications in this presentation and will identify those medications. • Applicable CME staff have no relationships to disclose relating to the subject matter of this activity. • This activity has been independently reviewed for balance. Learning Objectives • Discuss the relationship between insomnia and comorbid psychiatric disorders and the resulting implications for diagnosis and co-treatment • Evaluate current guideline recommendations for insomnia management with respect to the present standard of care and unmet needs with existing therapies • Review the latest clinical data surrounding the mechanisms of action and risk/benefit profiles of emerging pharmacotherapies for insomnia for informed therapeutic decision-making Mr. A • 58-year-old accountant, c/o unrefreshing sleep • Onset 4 months ago • Frequency 4 to 5 nights/week • Mind “spins” at bedtime • Feels washed out during day; low energy • Moody, irritable • Curtailed social activities • Medical history: Hypertension, controlled with losartan • Exam: Nl vital signs, BMI 38 • MSE: Psychomotor slowing; mood “fine”. Affect restricted, no h/s ideation, sensorium clear. Cognitive functions intact • Recent blood tests, including CBC, blood chemistry tests, LFTs, and TSH are WNL What additional criterion must be met to satisfy criteria for DSM-5 insomnia disorder? 1. -
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. -
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. -
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. -
ACNP 59Th Annual Meeting: Panels, Mini-Panels and Study Groups
www.nature.com/npp ABSTRACTS COLLECTION ACNP 59th annual meeting: panels, mini-panels and study groups Neuropsychopharmacology (2020) 45:1–67; https://doi.org/10.1038/s41386-020-00889-0 Sponsorship Statement: Publication of this supplement is sponsored by the ACNP. Individual contributor disclosures may be found within the abstracts. Asterisks in the author lists indicate presenter of the abstract at the annual meeting Study Group programs at UCLA and nationally. Dr. Shawn McClintock will present on how inclusion and diversity can be infused into the 1. Inclusion and Diversity Efforts Within Large Scientific continuing education and scientific programs as part of the ACNP Organizations: Tangible Methods: That Work conference, as well as strategies to translate knowledge from the conference to the membership’s place of work. Dr. Sade Spencer April Thames*, Sade Spencer, Lisa Eyler, Shawn McClintock, (co-Chair) will lead an interactive discussion and exercise to Erika Nurmi engage the audience in determining an action intention to take 1234567890();,: back with them to their spheres of influence based on what they Study Group Summary: Owing to the scarcity of women and have learned in the symposium. Overall, this timely and innovative underrepresented minorities in science especially in senior and work group sets the stage within and beyond the ACNP leadership roles, diversity and inclusion are aspirational “buzz- conference to ensure successful integration, implementation, words” that are used widely across institutions, organizational and long-lasting state-of-the-art diversity and inclusion practices. settings, and the scientific community. At federal, state and Disclosure: Nothing to disclose. private sector levels, billions of dollars have been allocated to “fix” this longstanding systemic problem. -
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.