The first patients have been enrolled into the Phase 3 registration program with nemorexant (proposed INN for ACT-541468), a dual orexin receptor antagonist, for the treatment of adult and elderly patients with insomnia, according to Idorsia Ltd. The Phase 3 program aims to confirm the positive results observed in the comprehensive Phase 2 clinical program in both adult and elderly patients with insomnia.
The registration program comprises two confirmatory studies together with a long-term extension study, which will recruit a total of 1,800 patients with insomnia from over 160 sites across 18 countries and is anticipated to run for around 2 years. As insomnia often presents later in life, around 40% of the recruited population will be aged 65 years and older. The program will investigate three doses (10 mg, 25 mg, and 50 mg), which were all effective and well tolerated in both adult and elderly patients studied in Phase 2. Patients will be treated for three months in the two trials, with the opportunity to continue treatment in a 40-week extension study.
Thomas Roth, PhD, director of the Sleep Disorder and Research Center at Henry Ford Hospital, says in a release, “Good quality sleep is vital to our physical and mental health. Poor quality sleep can affect many aspects of daily life, including the ability to concentrate, work effectively, and can impact social activities. Insomnia is a distinct disorder and not merely a symptom of other disorders. It is important to take it seriously and to help patients to fall asleep and stay asleep for the right amount of time thereby positively impacting their quality of life. There are treatments available to help insomnia but they may be associated with side effects, have limited efficacy, or are not suitable for long-term use.”
Martine Clozel, MD, Idorsia chief scientific officer, says, “Dual orexin receptor antagonism specifically targets excessive alertness, in contrast to treatments of insomnia that act via broad sedation of the CNS. As a result, nemorexant offers the potential to induce a normal sleep architecture with a maintained efficacy in chronic insomnia patients. The pharmacokinetic/pharmacodynamic profile of nemorexant, observed in patients with insomnia, is a direct result of our targeted approach, based on early use of modeling, to identify a compound with the optimal profile for a sleep medication.”
Idorsia has worked closely with patients to design the registration program through the development of a tailored patient-reported outcome instrument. This validated tool will be used to measure the impact of nemorexant on daytime performance. Idorsia will continue its patient focus through the conduct of a patient preference study. The aim of the study is to collect information on what patients consider important with regards to safety and efficacy of a sleep therapy.
Guy Braunstein, MD, head of global clinical development, says, “As shown in the Phase 2 study, nemorexant has the potential to offer the combination of fast onset of sleep, maintained efficacy throughout the night, without next-day residual effects. Our confirmatory Phase 3 registration program goes one step further: We will follow patients throughout the night and during the day, which will help us to characterize the impact of the condition on the daytime performance and how it is affected by the treatment. With the patient preference study, we will further the understanding of what is important to patients, in essence we will have a preferred benefit-risk profile from the patient’s perspective.”
The confirmatory multi-center, double-blind, randomized, placebo-controlled, parallel-group, polysomnography studies will assess the efficacy and safety of nemorexant on objective and subjective sleep and daytime functioning parameters in adult and elderly patients with insomnia disorder. The first study will evaluate treatment with 25 mg and 50 mg doses over 3 months, while the second study will measure treatment with 10 mg and 25 mg doses over 3 months. The 40-week extension study will measure all three doses, generating data for long-term treatment of insomnia.