Insomnia new drug daridorexant first Phase III trial results positive, significantly improve sleep quality

On April 20, The Swiss pharmaceutical company Idorsia announced that its candidate drug, the dual appetite receptor antagonist daridorexant, had been active in the first critical Phase III clinical trial for insomniacs, significantly improving sleep quality and daytime performanceUnlike previous studies, this time also evaluated the daytime performance after the treatment of insomnia, which is the traditional treatment of insomnia drugs will lead to a second day 'hangover' feeling, affecting normal working conditions, has been criticizedPhoto Source: Idorsia's websitesince the late 1990s, Idorsia has been developing daridorexant (formerly known as nemorexant), a double appetite receptor antagonistAppetite is a neuropeptide that regulates awakening and stimulates several signaling pathways that cause awakeningDaridorexant suppresses the overactive awakening pathway seroaheads insomniacs by blocking the function of appetiteThis is different from the mechanism of action of most sleep drugs, such as benzodiazepines, which cause patients to experience a "hangover" the next day by sedating the brain, i.edizziness, fatigue, fatigue and dysorientation due to the high concentration of the drug in the body memoryappetite stimulates multiple arousal signaling pathways (Photo: Idorsia.com)In the previous 2 studies, the researchers selected adults (64 years old) insomnia subjects to be randomized (1:1:1:1:1:1:1:1), daily oral placebo,dorexant(5, 10, 25 or 50mg) or zoldempi (zoldem) 10mgThe main effect is a change in the waking time from the baseline to the first and second days after the start of sleepSecondary efficacy indicators are changes in the continuous sleep incubation period from baseline to day 1 and 2, changes in subjective wakefulness time after sleep begins, and subjective incubation period from baseline to 4th week of sleepSecurity is also evaluatedIt was found that 359 of the 1,005 subjects (64% of women) were randomized and received a dose of 1 A significant dose-reactive relationship (two-sided P 0.001) found that a significant dose-response relationship was found on the basis of continuous sleep on the first and second days of sleep after reducing sleep starting, from the baseline to the first and second days of sleep These decreases continue until days 28 and 29 (P - 0.050 and P s 0.042, respectively) Similar dose-dependent relationships were observed for subjective awakening after sleep began and subjective incubation periods for sleep begin Among the subjects treated with 5, 10, 25 and 50 mg darid dorexant, the incidence of adverse events caused by treatment was 35%, 38%, 38% and 34%, respectively, compared with 30% for placebo and 40% for 10mg of pyretin There are no clinically related severe adverse events Four subjects withdrew from treatment due to adverse events Phase III enrollment program included two three-month confirmed studies and a 40-week expanded study that recruited about 1,800 insomnia patients (900 per study) from more than 160 sites in 18 countries the first Phase 3 clinical trial, which recruited 930 adults (39.1% to 65 years old) for insomnia, using two drug doses, 25 and 50 mg The researchers used polyguided sleep monitoring techniques to measure the time it takes to fall asleep and the time it takes to maintain sleep, the primary endpoint, and the total sleep and daytime performance were secondary endpoints, using the Sleep Time Symptoms and Impact Squestionnaire (IDSIQ) and sleep diaries Analysis of 1 and 3 months after treatment showed that daridorexant significantly improved the patient's sleep-starting and sleep-support IDSIQ is a specially developed questionnaire that evaluates not only nighttime sleep, but also daytime status safety, the placebo group and daridorexant had a similar incidence of adverse events at both doses During the study period, 37.7% of patients in the 25 and 50 mg daridorexant treatment groups had treatment-related adverse events (Treatment-emergent adverse, TEAE) and 34.0% in the placebo group The most common TEAE was nasopharyngitis and headache, with an incidence of more than 3%, higher than in the placebo group Compared to the daridorexant treatment group (2 5 mg, 2 cases; 50 mg, 3 cases), the number of severe adverse events in the placebo group was higher (7 cases) in addition, according to independent blind assessment, the underlying narcolepsy symptoms in all groups (which are used to indicate excessive sleep during the day) were balanced, and every morning the patient was evaluated by a visual simulation scale, no residual effect was found the following morning, and the patient did not experience reactive insomnia, or withdrawal symptoms after discontinuation, and no suicide, suicidal thoughts or self-harm were observed Show that the drug has important safety and tolerance Jean-Paul Clozel, M.D., and CEO of Idorsia, commented: 'Although we designed daridorexant as the best solution for sleep medicines, I was shocked by the results Once approved, Idorsia will have a significant impact on this medical, social and economic problem by providing daridorexant to millions of insomniacs Especially in this age of imprisonment in which we live, sleep is a major problem that requires a very safe and effective drug that can be used by many people With these results, Idorsia has entered a new era; less than three years into its existence, Idorsia is taking a big step towards becoming a mature biopharmaceutical company Dr Thomas Ross, director of the Center for Sleep Disorders and Research at Henry Ford Hospital, commented: 'Insomnia medication not only helps patients fall asleep quickly, stay sleep, but also addresses the negative effects of poor sleep on daytime function I believe that the best way to achieve this is to reduce excessive sobriety in insomniacs by blocking the effects of octreotide This will allow patients to fall asleep all night, while avoiding the adverse effects of many sleep medications through the extensive sedation of the brain The results seen in the three-month, three-part study show that daridorexant can meet this important need for insomniacs Dr Martine Clozel, chief scientific officer at Idorsia, said: 'Daridorexant was not discovered by accident, and our research team has been working very hard to find a double antagonist since it first studied appetitein and its receptors in 1998 Not only does this molecule work quickly, but its duration must also be characterized by "long enough at night and short enough during the day" to avoid any negative activity left on the morning of the following morning The results of this study we shared today are very valuable and prove that we have been on the right track for more than 20 years Guy Braunstein, M.D., , and head of global clinical development at Idorsia, commented: 'When designing our solutions, we must demonstrate the effectiveness of daridorexant on objective sleep measurements It's also very important for us that we have to provide what patients really need Therefore, the goal of the program is to determine whether Dalidosone can improve patients' perception of sleep and daytime performance To measure this, we developed and validated a specific patient reporting results tool This is a great commitment and we are confident that if any drug can show a positive impact, it is daridorexant We know that this information is missing from sleep science Guy Braunstein, , added: 'The results of this critical study are really striking about the consistency of the benefits of sleep ingress In addition, this is the first study to demonstrate that insomnia products can improve daytime sensationin in patients If you ask anyone with insomnia, that's what they want -- sleep longer and feel better during the day Daridorexant is solving the real problem sqisof When you see that the effect does not affect safety, the effect is more significant We are now looking forward to the results of the second key study of Daridorexant 10 and 25 mg The results of the second validation Phase III study of daridorexant, which measures three doses of 10, 25 and 50 mg and is also in March, are expected to be announced later this year, Idorsia said If all goes well, the company will apply to the U.S FDA for approval by the end of 2020 the second randomized controlled trial was also a multicenter, double-blind, randomized, placebo-controlled, parallel group, multicenter study that assessed the efficacy and safety of daridorexant's objective and subjective sleep and daytime performance parameters for adult and elderly insomniacs The published results of Phase 1, Phase 3, assessed 25 mg and 50 mg dose therapy for 3 months, while the second study will evaluate 10 mg and 25 mg dose therapy for 3 months and are expected to report the results in the third quarter of 2020 it's worth noting that Idorsia will also conduct an extended 40-week study to assess the efficacy of three doses of daridorexant and obtain data on the drug's long-term treatment of insomniacpatients Expect this treatment to be a better choice for insomniacs about 30 percent of adults worldwide suffer from insomnia, most of whom have insomnia symptoms that last for months to years Currently, two appetite receptor antagonists have been approved to treat insomnia clots worldwide, Belsomra of Mersadon (detailed report: Mersadon insomnia drug Belsomra has finally been approved by the FDA - how to break out into a new challenge ) and Wesfarmers' Dayvigo (detailed report: insomnia treatment is dawning: FDA approved for The vigo ) References: 1 Dau villiers Y, Zammit G, Fietze I, Mayleben D, Seboek Kinter D, Pain S, Hedner J DDororexant, a New Dual Orexin Eid Ingatagonist to Treat Insomnia.
Ann 2020 Mar;87 (3):347-356 doi: 10.1002/ana.25680 2 Idorsia's Drug Improves Sleep in First Phase III Trial for Insomnia (Source: LABIOTECH.eu) 3 Idorsia announces s positive results in the first Phase 3 study of dorexant with improved overall sleep and daytime performance of patients with insomnia (source: Idorsia official website) 4 Idorsia Company Presentation (Source: Idorsia) Author: MedSci Source: MedSci Original