Summary:
In the SYMPHONY stage 3 trial, Axsome Therapeutics’ AXS-12 considerably lowered weekly cataplexy assaults and improved indications of narcolepsy, which include extreme daytime sleepiness, cognitive operate, and over-all ailment severity, when compared to placebo. The examine, which included 90 individuals, also observed remission of cataplexy in a third of AXS-12 dealt with clients. The company programs to present detailed results at upcoming scientific conferences.
Crucial Points:
- AXS-12 statistically considerably lessened cataplexy attacks in comparison to placebo.
- AXS-12 achieved statistically considerable remission of cataplexy as opposed to placebo.
- AXS-12 statistically significantly decreased extreme daytime sleepiness severity.
- AXS-12 statistically considerably enhanced focus and memory in contrast to placebo.
- AXS-12 statistically noticeably diminished the over-all severity of narcolepsy when compared to placebo.
- AXS-12 statistically significantly improved general operate and high-quality of everyday living when compared to placebo.
In the SYMPHONY phase 3 demo, Axsome Therapeutics’ AXS-12 (reboxetine), a highly selective and potent norepinephrine reuptake inhibitor and cortical dopamine modulator, achieved its principal endpoint by considerably cutting down the frequency of cataplexy assaults in narcolepsy patients.
AXS-12 also diminished abnormal daytime sleepiness severity, improved cognitive function, and decreased general narcolepsy severity as as opposed to placebo. SYMPHONY was a period 3 multicenter, randomized, double-blind, placebo-managed trial in which 90 clients with a diagnosis of narcolepsy with cataplexy were randomized to remedy with AXS-12 or placebo for 5 weeks.
“The SYMPHONY period 3 demo outcomes confirm the promise and probable of AXS-12 for the therapy of narcolepsy,” suggests Herriot Tabuteau, MD, CEO of Axsome Therapeutics, in a launch. “Treatment with AXS-12 resulted in rapid and substantial reduction of cataplexy activities, the main endpoint of the SYMPHONY trial, even though evidencing enhancement throughout a variety of validated global medical, patient-noted, top quality of existence, and functional end result measures.”
SYMPHONY Section 3 Trial Effects
- AXS-12 fulfilled the principal endpoint by demonstrating a substantial and statistically important reduction from baseline in weekly cataplexy assaults in comparison to placebo at week 5, with reductions of 83% for AXS-12 and 66% for placebo (p=.018). AXS-12 promptly reduced weekly cataplexy assaults, demonstrating at 7 days 1 a reduction of 56% in contrast to a reduction of 31% for placebo (p=.007).
- AXS-12 induced remission of cataplexy and greater cataplexy-absolutely free times in contrast to placebo. Remission of cataplexy, described as a 100% reduction from baseline, was reached at 7 days 5 by 33% of AXS-12 addressed clients when compared to 9.5% of placebo sufferers (p=.008). Accomplishment of remission was swift, staying professional at 7 days 2 by 24% of AXS-12 addressed sufferers as opposed to 4.5% of placebo people (p=.008). AXS-12 elevated the share of cataplexy-free times for each 7 days, outlined as days with zero cataplexy assaults, to 84.5% at 7 days 5 compared to 22.6% for placebo (p=.014).
- AXS-12 noticeably decreased extreme daytime sleepiness severity, assessed by the Clinician International Impression of Severity scale for extreme daytime sleepiness, in contrast to placebo at 7 days 5 with signify reductions of 1.8 factors for AXS-12 when compared to .9 points for placebo (p=.027). Fast advancement on the Clinician International Perception of Severity scale for abnormal daytime sleepiness was observed as early as 7 days 1 as opposed to placebo (p=.006).
- AXS-12 concurrently improved excessive daytime sleepiness and cataplexy as as opposed to placebo. Concurrent excessive daytime sleepiness and cataplexy reaction was attained at 7 days 5 by 57% of clients dealt with with AXS-12 compared to 33% of placebo sufferers (p=.029). Concurrent EDS and cataplexy reaction was described as a ≥30% reduction in inadvertent naps (abnormal daytime sleepiness reaction), and a ≥50% reduction in cataplexy assaults (cataplexy response).
- A reduce in the number of inadvertent naps was professional by 54% of AXS-12 people at week 5 as opposed to 28% of placebo sufferers (p=.016), assessed by the Narcolepsy Symptom Evaluation Questionnaire. Advancement on the Epworth Sleepiness Scale was numerically greater for AXS-12 than for placebo, with mean reductions from baseline of 4.7 points for AXS-12 compared to 3.4 details for placebo. A ≥3-stage advancement from baseline on the Epworth Sleepiness Scale was accomplished by 60% of AXS-12 individuals who had a cataplexy response.
- AXS-12 substantially enhanced focus and memory as measured by the Cognitive Perform Things of the Practical Outcomes of Slumber Questionnaire at 7 days 5 (p=.004). AXS-12 concurrently improved cognition and cataplexy as in contrast to placebo. Concurrent cognitive and cataplexy response was achieved at 7 days 5 by 41% of people handled with AXS-12 compared to 17% of placebo clients (p=.016). Response was described by an enhance in days sufferers rated their Capacity to Focus as extremely good or fantastic (cognitive reaction), and a ≥50% reduction in cataplexy attacks (cataplexy response).
- AXS-12 enhanced narcolepsy overall disorder problem and affected individual purpose and good quality of life. Clinicians documented a swift and major reduction in overall narcolepsy severity for clients treated with AXS-12 when compared to placebo at 7 days 5 (p=.007), with advancements noticed as early as Week 1 (p<0.001). AXS-12 demonstrated significant improvement in overall patient function and quality of life as measured by the Functional Outcomes of Sleep Questionnaire total score as compared to placebo at Week 5 (p=0.005).
- Anxiety and depression, known common narcolepsy co-morbidities, was reported by 45% of study participants at baseline, as assessed by the EuroQol. Improvement from baseline in the Anxiety/Depression domain of the EuroQol was achieved by 55% of patients treated with AXS-12 compared to 32% of placebo patients (p=0.146).
- AXS-12 was well tolerated in the trial. The most commonly reported adverse events in the AXS-12 arm were dry mouth (n=6), nausea (n=6), and constipation (n=4), which were overall mild to moderate. The rates of discontinuation due to adverse events was low (n=1 in each of AXS-12 and placebo arms). There were no serious adverse events in the trial.
AXS-12 was granted Orphan Drug Designation for the treatment of narcolepsy in October 2018.
“Collectively, the data generated in SYMPHONY highlight AXS-12’s positive therapeutic impact and are consistent with the results from the previously completed positive CONCERT trial. As a next step, we look forward to completing the ongoing open-label safety extension trial of AXS-12 as we work to bring this treatment to individuals living with narcolepsy,” says Herriot Tabuteau, MD, CEO of Axsome Therapeutics, in a release.
Axsome plans to present the detailed results of the SYMPHONY trial at upcoming scientific meetings.
“Despite the existence of multiple approved narcolepsy treatments, significant unmet need still exists given the high rates of persistent symptoms reported by patients. Based on the concurrent improvements observed on cataplexy, severity of excessive daytime sleepiness, cognition and overall function, I believe AXS-12 represents a meaningful enhancement to the treatment armamentarium for narcolepsy patients and clinicians and will be a welcome treatment option in our fight against the devastating impact of narcolepsy on patients and their loved ones,” says Michael Thorpy, MD, director of the Sleep-Wake Disorders Center at the Montefiore Medical Center and professor of neurology at Albert Einstein College of Medicine.
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