INNOVATION & PIPELINE
For the treatment of Insomnia and Mood Disorders
Seltorexant is an innovative selective orexin 2 receptor antagonist under development for the treatment of insomnia and related mood disorders. Insomnia is the repeated difficulty with sleep initiation, maintenance or quality that occurs despite adequate time and opportunity for sleep, resulting in daytime impairment. Insomnia can be the primary condition for patients or a secondary symptom of, and contributor to, another medical or psychiatric condition, such as mood disorders or schizophrenia.
In the brain, the orexin system is involved in the control of several key functions, including metabolism and wakefulness. Seltorexant seeks to inhibit the activity of the neurons that promote wakefulness by selectively blocking the orexin 2 receptor. Rather than making an individual sleepier, blocking the orexin 2 receptor reduces the level of the neurotransmitters that signal the brain to maintain vigilance and wakefulness, which can be helpful for patients with insomnia. In addition, we believe this approach may help preserve physiologic and restorative sleep, with improved safety and tolerability over current treatments. Recent research also shows that the orexin system affects the secretion and control of stress hormones like the ones involved in the hypothalamic-pituitary-adrenal or HPA axis (e.g., adrenocorticotropic hormone and cortisol). The HPA axis is known to be overactive in depressed patients a significant proportion of whom suffer from insomnia. We are jointly developing Seltorexant under a co-development and license agreement with Janssen Pharmaceutica N.V., a Johnson & Johnson company.
Recent Developments and Next Steps
In September 2017, we announced the enrollment of the first patient in a Phase 2b clinical trial of seltorexant as adjunctive therapy to antidepressants in adult patients with major depressive disorder (MDD) who have responded inadequately to antidepressant therapy.
The primary objectives of this multi-center, double-blind, randomized, parallel group, placebo-controlled, adaptive-dose finding study are to assess the dose-response relationship and antidepressant effects of up to three doses of seltorexant, and to assess the safety and tolerability of seltorexant compared to placebo as described in clinicaltrials.gov: NCT03227224.
The trial consists of three phases: a screening phase lasting up to four weeks, a six-week double-blind treatment phase and a two-week post-treatment follow-up phase. Approximately 280 patients are planned to be enrolled at more than 85 clinical sites in the U.S., Europe, Russia and Japan.
In December 2017, we announced the enrollment of the first patient in a Phase 2b clinical trial of seltorexant in patients with insomnia disorder (NCT03375203). This multicenter, double-blind, randomized, parallel-group, active- and placebo-controlled dose finding study is designed to assess the efficacy and safety of seltorexant in both adult and elderly subjects with insomnia disorder. The primary objective of this trial is to assess the dose-response of three doses of seltorexant (5, 10 and 20 milligrams daily) compared to placebo on sleep onset as measured by the latency to persistent sleep (LPS) using polysomnography (PSG). The key secondary objective is to assess the dose-response of these three doses compared to placebo on wake after sleep onset (WASO) over the first six hours using PSG. In addition, the effects of seltorexant on sleep and cognition will be compared to those effects of zolpidem to determine potential differences between the compounds.
A total of approximately 360 patients 18 to 85 years of age will be randomized in this study at clinical sites in the United States, European Union and Japan. The duration of participation in this study for an individual subject will be up to 61 days, including screening and follow-up.
In December 2017, we announced the enrollment of the first patient in a Phase 2b clinical trial (NCT03321526) comparing seltorexant versus quetiapine as adjunctive therapy in patients with major depressive disorder (MDD) who have responded inadequately to antidepressant therapy.
The primary objective of this multi-center, double-blind, randomized, flexible-dose, parallel-group study is to assess the efficacy of flexibly dosed seltorexant compared to flexibly dosed quetiapine as adjunctive therapy to a baseline antidepressant drug in delaying time to all-cause discontinuation of study drug over a 6-month treatment period. Time to all-cause discontinuation is defined as the number of days from administration of the first dose of study drug to administration of the last dose of study drug.
The trial consists of three phases: a screening phase lasting up to four weeks, a six-month double-blind treatment phase and a two-week follow-up phase. Approximately 100 patients 18 to 64 years of age are planned to be randomized at approximately 34 sites in the U.S. to receive either flexibly dosed seltorexant, 20 milligrams (mg) or 40 mg, or flexibly dosed quetiapine XR, 150 mg or 300 mg. Subjects will continue to take their baseline antidepressant therapy of either an SSRI (selective serotonin reuptake inhibitor) or an SNRI (serotonin-norepinephrine reuptake inhibitor) at the same dose throughout the screening, double-blind and follow-up phases.