ACT-541468 (DORA) meets primary endpoint in Phase 2 program in adult and elderly patients with insomnia

  • Results show desired effect on sleep maintenance and onset - significant dose-response relationship
  • Idorsia to advance ACT-541468 (DORA) into confirmatory Phase 3 program

Allschwil, Switzerland - 28 July 2017 - Idorsia Ltd (SIX: IDIA) today announced positive results for the comprehensive Phase 2 program with the dual orexin receptor antagonist ACT-541468 (DORA) in insomnia, with zolpidem as an active reference. The program comprised two placebo-controlled dose-response studies to evaluate the safety and efficacy of ACT-541468 in adult and elderly patients with insomnia, with a total of 418 patients participating in the trials.

Martine Clozel, MD and Chief Scientific Officer of Idorsia, commented: "Our scientists have been true pioneers in the field of orexin antagonism. More than 20000 compounds were synthesized and studied before ACT-541468 was selected. Its discovery is the result of an extensive effort to combine two important characteristics of a sleep medication: maintaining efficacy throughout the night, and a low potential for a next-day residual effect. I am delighted to see that the positive readouts from this comprehensive Phase 2 program are consistent with our preclinical predictive models, for both adult and elderly patients with insomnia."

The first study in 360 adults (ranging from 18 to 64 years) with a treatment duration of 4 weeks showed a significant dose-dependent decrease in WASO at Day 1 & 2 (average decrease of wake time after sleep onset from baseline on the first 2 nights of treatment, measured by polysomnography). In addition, ACT-541468 significantly decreased LPS (latency to persistent sleep) in a dose-dependent manner.

Treatment with ACT-541468 was generally well tolerated. There were no reports of serious adverse events related to ACT-541468.

The positive readouts of a second study, conducted in 58 elderly patients (ranging from 65 to 85 years), confirmed the efficacy and safety profile of ACT-541468 in this population. The results of this study also showed a significant decrease in WASO and LPS at Day 1 & 2 in a dose-dependent manner.

The overall results of the Phase 2 program with ACT-541468 in insomnia support the decision to initiate efficacy and safety confirmatory studies in both adult and elderly patients.

Detailed results of the Phase 2 program will be made available through scientific disclosure at upcoming congresses and in peer-reviewed publications. 

Guy Braunstein, MD and Head of Global Clinical Development of Idorsia, commented: "The positive results of the Phase 2 program demonstrate that our DORA can deliver on the potential its mechanism of action offers in insomnia. We have observed a fast onset of sleep and a duration of action which does not exceed a normal night's sleep. We will now consult with health authorities and progress this important asset into the Phase 3 program as quickly as possible."

Jean-Paul Clozel, MD and Chief Executive Officer of Idorsia, commented: "We couldn't have asked for a better start for Idorsia. First the excellent results with aprocitentan, where we are in discussions with health authorities to move into Phase 3 for development in resistant hypertension, and now our dual orexin receptor antagonist moving into Phase 3 for insomnia. This will take us an important step closer to delivering on one of our major strategic objectives - to bring at least three products to market within the next 5 years that have the potential to substantially change the treatment options in their target disease."


Notes to the editor

About ACT-541468 (DORA)

ACT-541468 is a dual orexin receptor antagonist (DORA) which targets the orexin system and is intended to treat insomnia. Based on preclinical data, dual orexin receptor antagonism maintains natural sleep architecture. Preclinical data suggests that ACT-541468 will have a low potential for abuse. Data from a comprehensive Phase 1 program indicates that ACT-541468 has a suitable pharmacokinetic and pharmacodynamic profile to deliver fast onset of sleep, a duration of action which is well suited for appropriate sleep maintenance, and low potential for next day residual effect. These properties are being explored clinically and, if confirmed, will give ACT-541468 the potential to be differentiated from current sleep medications, for the benefit of patients.

About Orexins

Orexins are neuropeptide modulators - small protein-like molecules used by nerve cells (or neurons) to communicate with each other in the brain. Orexins act functionally at the interface of alertness, energy homeostasis and reward: aversion systems, essentially to regulate vigilance and alertness states. Defects of the orexin peptides, or their receptors, are associated with wakefulness and sleep disorders.

The anatomical distribution of orexin receptors in the brain supports the essential role that orexin plays in promoting alertness and maintaining wakefulness under situations of high motivational relevance, e.g. circadian vigilance states, reward opportunities or exposure to threats. Orexins and their receptors are highly conserved across vertebrate species.

About Insomnia

Insomnia is defined as a combination of both dissatisfaction with sleep and a significant negative impact on daytime functioning. Dissatisfaction with sleep describes 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 sleeping disorder. By 2020, it is estimated that there will be approximately 13 million insomnia patients being treated with pharmaceutical-grade insomnia medications in the US alone, according to research by GlobalData Ltd in 2015.

Lack of sleep can have a significant negative impact on daytime functioning, physical and mental health. This can include fatigue, daytime sleepiness, poor concentration, depressed mood, or impaired ability to perform social or occupational tasks.

The goal of treatments for insomnia is to improve sleep quality and quantity, as well as reducing insomnia-related daytime impairments, while being safe and devoid of any next morning residual effect. Current treatment of insomnia includes cognitive behavioral therapy, sleep hygiene recommendations, and pharmacotherapy. Most sleep disorder products on the market enhance the effects of gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. Such medications are associated with side effects such as next-day effects, anterograde amnesia, and risk of tolerance and dependence.

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 intend to develop Idorsia into Europe's leading biopharmaceutical company, 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 600 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 

This document does not constitute an invitation or an offer to purchase, sell, trade or subscribe for any shares or other securities of the companies involved. Furthermore, this document is neither a prospectus according to Art. 652a of the Swiss Code of Obligations nor a listing prospectus according to the listing rules of SIX Swiss Exchange Ltd.

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.