Gudeman, Jennifer

Abstract Introduction Individuals with narcolepsy were surveyed to better understand desired treatment outcomes and how those outcomes map to commonly experienced symptoms, treatment awareness, and medication usage. Methods In February 2022, an email invitation to a 27-question online survey was sent to US members of MyNarcolepsyTeam, a social network of >9,800 members. Results In total, 110 members completed the survey. The most frequently mentioned desired treatment goals aligned with the most commonly reported symptoms: being able to stop sleeping during the day (77%); increased energy (62%); improved memory (36%); improved productivity (29%); improved sleep continuity (22%); and for patients with narcolepsy type 1, reducing cataplexy (28%). A common theme was desire for a medication that would treat the underlying cause and not just improve specific symptoms. In one patient’s own words: “I want to see treatments that target the root problem of poor nighttime sleep rather than just being a band-aid for [excessive daytime sleepiness] EDS, like stimulants are.” Only a small percentage of respondents (13%) were not currently taking any type of medication to address narcolepsy symptoms. 64% were currently taking ≥2 medications to address both the daytime and nighttime symptoms. Most commonly mentioned current treatments were dextroamphetamine-amphetamine (30%), modafinil (22%), melatonin (16%), armodafinil (15%), venlafaxine (14%), and oxybate (14%). Notably, 33% of patients taking sodium oxybate chose sleeping through the night as a desired outcome. Most common sources for learning about treatments were narcolepsy-specific websites (53%), MyNarcolepsyTeam specifically (45%), the patient’s doctor (42%), scientific articles (42%), and advocacy groups (37%). Conclusion Patients experience a wide range of both daytime and nighttime symptoms and seek relief from both sets of symptoms including EDS (93%), fatigue (79%), cognitive challenges (74%), as well as sleep disruptions (63%). As a result, the majority need multiple medications. Understanding the experiences and needs of people with narcolepsy provides significant opportunities for clinicians to support, educate, and treat their patients holistically. Additionally, content readily available on the internet, whether it is narcolepsy-specific content or social networks, helps patients proactively discuss options with their clinician. Support (if any) Avadel Pharmaceuticals

Abstract Introduction Sodium oxybate (SXB) is strongly recommended for treatment of narcolepsy. Patients treated with available immediate-release oxybates are required to awaken for a second dose 2.5–4 hours after the bedtime dose to cover a full night of sleep. This study characterized SXB treatment patterns and discontinuation in narcolepsy patients. Methods Mayo Clinic patients from 1975–2020 were identified using an electronic health record–based search. Patients with ≥1 narcolepsy-specific ICD-9/-10 code and ≥1 diagnostic mention of narcolepsy in clinical notes (identified using a natural-language-processing [NLP] algorithm) were included. NLP was used to identify SXB non-use events with manual chart reviews performed to characterize reasons for discontinuation, switching, or missing the second dose and effects of missing the second dose. Results Of the patients with narcolepsy prescribed SXB (n=351; mean age at first diagnosis code observed at Mayo Clinic, 32 y [IQR: 23.2–46.1]; 65.5% female; 92.3% white), 113 (32.2%) had clinical notes indicating discontinuation of SXB, with 71 (20.2%) including reasons for discontinuation. The most common reasons for discontinuation (n≥5) included lack of efficacy (n=11), side effects (n=10), gastrointestinal side effects (n=10), neurological side effects (n=9), psychiatric side effects (n=8), lack of access (insurance/cost, n=10), and resolution/absence of cataplexy (n=5). Mentions of switching from SXB to other drugs (n=12 patients) included switching to stimulants (mixed amphetamine salts, n=3; dextroamphetamine, n=2; methylphenidate, n=1), sedative hypnotics (zolpidem, n=2), antidepressants (mirtazapine, n=1), and wake-promoting agents (solriamfetol, n=1). Of the 38 patients (10.8%) with mentions of missing the second nightly SXB dose, reasons were recorded for 24 (63.2%), including inability to wake up (n=14), forgetting the second dose (n=3), and having to wake up early the following day (n=3). Consequences of missing the second dose were recorded for a small subset (increased cataplexy, n=4; lower daytime alertness, n=3; awakens earlier, n=1; tiredness, n=1). Conclusion Limited data are available regarding real-world use of SXB. This novel study used a combination of NLP algorithm and manual chart review to identify difficulties patients have with the second, middle-of-the night immediate-release oxybate dose and patient-experienced consequences of not adhering to the prescribed dosing regimen. Support (if any) Avadel Pharmaceuticals

Abstract Introduction Narcolepsy is a rare, chronic sleep disorder whose symptoms detrimentally impact quality of life. Narcolepsy has a complex phenotype associated with multiple comorbid conditions. This is the first study to use aggregate electronic health record (EHR) data to characterize the demographics and comorbidities of patients with narcolepsy. Methods An EHR-based search identified first-time Mayo Clinic patients between 2000–2020. Included patients had ≥1 narcolepsy-specific ICD-9/10 code and ≥1 disease-supportive statement in the clinical notes (identified using a natural language processing algorithm). A control cohort was propensity-matched for birth year, age at first institutional encounter, sex, race, ethnicity, number of diagnosis codes, and mortality. Common comorbidities were compared and ranked between cohorts by odds ratio (OR); P values were adjusted and calculated based on Bonferroni correction. Results In the EHR database (N=6,389,186 patients), 2057 patients with narcolepsy were identified (median age at first presentation to Mayo clinic, 32 y [range, 17–48]; 59.6% female; 92.6% white; 89.2% non-Hispanic) and propensity-matched with a control cohort of 2057 patients (median age at first presentation to Mayo clinic, 35 y [range, 12–52]; 58.9% female; 94.6% white; 84.5% non-Hispanic). Among the top comorbidities that occurred more frequently in the narcolepsy cohort compared to the control cohort (OR [95% CI]; P< 0.001]) were sleep disorders (restless leg syndrome, 3.94 [3.09–5.02]; obstructive sleep apnea, 3.27 [2.83–3.79]; insomnia, 1.84 [1.57–2.17]); mood disorders (depression, 2.11 [1.86-2.40]; dysthymia, 1.86 [1.54–2.25]; anxiety, 1.67 [1.46–1.89]); and pain disorders (chronic pain syndrome, 2.20 [1.76–2.76]; migraine, 1.96 [1.66–2.31]; fibromyalgia, 1.90 [1.61–2.25]; carpal tunnel syndrome, 1.80 [1.46–2.22]; myalgia, 1.69 [1.45–1.97]). Other comorbidities statistically significantly associated with narcolepsy were (OR range, 1.33–1.95) irritable bowel syndrome (P< 0.001), asthma (P< 0.001), cervical spondylosis (P< 0.01), syncope (P< 0.01), and hypothyroidism (P< 0.05). Conclusion This propensity-matched cohort study affirmed prior studies of increased psychiatric and sleep disorders in patients with narcolepsy. Narcolepsy patients were twice as likely to experience chronic pain syndrome compared to the matched control group. Understanding common narcolepsy comorbidities may help optimize treatment efficacy and increase understanding of the medical/psychiatric challenges of narcolepsy patients. Support (if any) Avadel Pharmaceuticals

Abstract Introduction Extended-release once-nightly sodium oxybate (ON-SXB; FT218) is in development for adults with narcolepsy. In REST-ON, significant improvements on the Maintenance of Wakefulness test, Clinical Global Impression of Improvement rating, and number of weekly cataplexy episodes occurred with all analyzed ON-SXB doses vs placebo (week 3, 6-g dose; week 8, 7.5-g dose; week 13, 9-g dose; all P<0.001). ON-SXB was superior to placebo on Epworth Sleepiness Scale (ESS) score and sleep quality and refreshing nature of sleep using visual analog scales (VAS; all P<0.001). ON-SXB 4.5 g significantly reduced cataplexy episodes vs placebo at week 1 (P<0.05). Post hoc analyses investigated ON-SXB efficacy on ESS score, VAS sleep quality, and VAS refreshing nature of sleep at weeks 1 and 2. Methods Participants in the double-blind, phase 3 REST-ON (NCT02720744) trial were ≥16 years old, had narcolepsy type 1 or 2, and were randomized 1:1 to ON-SXB (4.5 g, 1 week; 6 g, 2 weeks; 7.5 g, 5 weeks; 9 g, 5 weeks) or placebo. Participants recorded ESS scores and VAS for sleep quality and refreshing nature of sleep (1-100; 1=poor quality/unrefreshing sleep; 100=good quality/refreshing sleep) using electronic diaries. P-values were calculated using a mixed-effects model for repeated measures in the modified intent-to-treat (mITT) population (ie, participants receiving ≥1 dose of study drug having ≥1 efficacy assessment at week 3). Results In the mITT population (n=190; ON-SXB, n=97; placebo, n=93), baseline ESS scores were 16.6 and 17.5 with ON-SXB and placebo, respectively. At week 2, ESS score was significantly improved with ON-SXB vs placebo (P<0.02) with numerical improvement seen at week 1. At baseline, sleep quality was 53.8 and 55.9 on VAS in the ON-SXB and placebo groups, respectively, and baseline refreshing nature of sleep was 46.5 and 49.9. At weeks 1 and 2, sleep quality (P<0.01; P<0.001) and refreshing nature of sleep (P<0.05; P=0.001) were significantly improved for ON-SXB vs placebo. Conclusion Improvement in daytime sleepiness, sleep quality, and refreshing nature of sleep occurred with ON-SXB beginning the first week of treatment. Some patients may experience early narcolepsy symptom relief with ON-SXB. Support (If Any) Avadel Pharmaceuticals

Abstract Introduction Immediate-release sodium oxybate (SXB) and mixed-salt oxybates require patients with narcolepsy to take a second nightly dose 2.5–4 h after the first. Extended-release, once-nightly SXB (ON-SXB; FT218) is an investigational treatment for adults with narcolepsy. Surveys evaluated patient and healthcare provider (HCP) perspectives on narcolepsy disease burden and satisfaction with current narcolepsy treatment options. Methods Individuals with narcolepsy and HCPs participated in 30-minute, web-based surveys. Participants were 1) adults with self-reported, physician-diagnosed narcolepsy for ≥1 year, and prior/current/no use immediate-release oxybates; and 2) board-certified/board-eligible HCPs (pulmonology, sleep medicine, neurology, psychiatry specialties); nurse practitioners; or physician assistants. Participants responded using 9-point scales; higher scores indicated greater severity/agreement/satisfaction/importance/preference. Results Mean patient participant (n=120) age was 40 years; most were white (81%), female (79%), and current/past users of twice-nightly SXB (n=86) or mixed-salt oxybates (n=56). Twenty-six were oxybate naive. Most HCPs (n=100; 68% male) had sleep medicine (37%) or neurology (30%) specialties; 91% and 83% had experience with twice-nightly SXB and mixed-salt oxybates, respectively. Patients and HCPs agreed that patients preferred narcolepsy treatments dosed fewer times (rated 6.7 and 7.7, respectively). Common symptoms patients experienced daily/almost daily at narcolepsy diagnosis were tiredness/fatigue (64%) and excessive daytime sleepiness (EDS; 68%). HCPs and patients expressed moderate-to-high satisfaction with mixed-salt oxybates (both 7.1) and twice-nightly SXB (6.8 and 6.6, respectively). Compared to HCPs, patients were less satisfied with modafinil (6.9 vs 4.5), armodafinil (6.9 vs 4.8), solriamfetol (6.8 vs 5.4), and pitolisant (6.6 vs 5.2). Twice-nightly SXB and mixed-salt oxybates received high ratings from patients and HCPs for reduction of cataplexy (patients: 7.3 and 7.4; HCPs, 6.7 and 6.8) and EDS (patients: both 7.0; HCPs, both 6.9). Lower satisfaction was reported for twice-nightly SXB and mixed-salt oxybates with dosing frequency (patients, 5.4 and 6.0; HCPs, 5.9 and 6.3) and medication taste (patients, 5.3 and 5.7; HCPs, 5.9 and 6.2). Conclusion While both individuals with narcolepsy and HCPs are relatively satisfied with current narcolepsy treatments, both groups are less satisfied with the dosing frequency of currently approved oxybate formulations. ON-SXB will be an additional treatment option that can address this unmet need. Support (If Any) Avadel Pharmaceuticals

Abstract Introduction Currently available immediate-release sodium oxybate (SXB) and mixed-salt oxybates are dosed twice nightly (second 2.5–4 hours after first). Extended-release, once-nightly SXB (ON-SXB; FT218) is in development. To characterize drivers of oxybate treatment attribute preferences, discrete choice experiments (DCEs) were conducted for both patients and healthcare providers (HCPs). Methods Thirty-minute web-based surveys were fielded to 1) adults with self-reported physician-diagnosed narcolepsy with/without prior/current use of oxybate, and 2) board-certified/board-eligible HCPs treating ≥5 narcolepsy patients in the last month. Choice sets of 2 hypothetical treatment profiles were generated combining attributes of twice-nightly SXB, mixed-salts oxybate, and ON-SXB. While viewing 12 choice sets, each participant indicated (1) their preferred product overall, (2) the product that would improve quality of life (QoL), and (3) the product that would result in less patient stress/anxiety. Results were analyzed using a mixed logit model. Results For patients (n=120) and HCPs (n=100), the most important attribute driving overall product choice was dosing frequency (relative attribute importance, 26.0 and 46.1, respectively), with once-nightly preferred over twice-nightly dosing (relative preference weight, ±25.6 and ±43.6); QoL (relative attribute importance, 28.7 and 41.7), with once-nightly preferred over twice-nightly dosing (relative preference weight, ±25.7 and ±38.5); and reducing patient anxiety/stress (relative attribute importance, 26.7 and 44.0), with once-nightly preferred over twice-nightly dosing (relative preference weight, ±23.9 and ±41.6). Other drivers of overall product choice were as follows: patients, clinical efficacy and sodium content (relative attribute importance, 23.5 and 20.8); HCPs, adverse reactions and sodium content (relative attribute importance, 19.7 and 18.6). Drivers of QoL preference were as follows: patients, clinical efficacy and sodium content (relative attribute importance, 28.3 and 20.9); HCPs, adverse reactions and clinical efficacy (relative attribute importance, 21.5 and 18.6). Drivers of reducing patient anxiety/stress were as follows: patients, clinical efficacy and sodium content (relative attribute importance, 17.4 and 17.3); HCPs, adverse reactions and sodium content (relative attribute importance, 18.2 and 14.2). Conclusion Dosing frequency was identified as the most important attribute driving preference for overall product choice, QoL, and reducing patient anxiety/stress for both patients and HCPs with once-nightly preferred over twice-nightly dosing. Support (If Any) Avadel Pharmaceuticals