Gudeman, Jennifer

Abstract Introduction Once-nightly sodium oxybate (ON-SXB) is approved to treat cataplexy or excessive daytime sleepiness (EDS) in patients ≥7 years of age with narcolepsy. ON-SXB demonstrated significant improvements in both objective (Maintenance of Wakefulness Test) and subjective (Epworth Sleepiness Scale [ESS] score) measurements of sleepiness in the REST-ON trial and via the ESS in the real-world REFRESH study. Assessing ON-SXB ESS data from a specialty pharmacy and outside of clinical studies further informs the generalizability of effectiveness. Methods Demographic and clinical data were collected from Optum Frontier Therapies pharmacy for patients with ≥1 filled ON-SXB prescription, ≥1 ON-SXB-related clinical assessment, and ≥1 follow-up ESS score (6/1/2023-9/30/2024). Participation in ESS assessment was voluntary. ESS scores were assessed for patients who switched from twice-nightly oxybate (TN-OXB) treatment (first ON-SXB prescription filled ≤30 days of last TN-OXB prescription [switch]) and those new to oxybate or with >30 days between TN-OXB and ON-SXB prescription fills (not-on-oxybate) who had ESS data at initial ON-SXB prescription and at each follow-up assessment. Results Of 452 identified patients, 215 had ≥1 follow-up ESS score (switch, n=82 [mean age, 38.4 years; female, 71%]; not-on-oxybate, n=133 [mean age, 40.0 years; female, 71%]). Of patients who had any prior oxybate use (switch, 100%; not-on-oxybate, 46%), the most common prior oxybate was mixed-salt oxybates (switch, 59%; not-on-oxybate, 70%). Stimulants/wake-promoting agents were taken by 51% of switch and 65% of not-on-oxybate patients. Baseline mean (SD) ESS scores were 11.3 (5.5) for switch and 12.5 (5.6) for not-on-oxybate patients; 23% of switch and 38% of not-on-oxybate patients experienced severe EDS. By the first follow-up (median [IQR], 49 [28-94] days), mean (SD) ESS scores were within the normal EDS range with ON-SXB for both subgroups (ie, ESS < 10; switch, 9.7 [5.5]; not-on-oxybate, 9.5 [5.2]); the majority reported normal levels of daytime sleepiness (switch, 56%; not-on-oxybate, 57%). Mean (SD) change in ESS score from baseline to follow-up was -1.6 [4.5] for switch and -3.1 [5.0] for not-on-oxybate groups. Conclusion Patients who initiated ON-SXB experienced improvements in daytime sleepiness regardless of prior TN-OXB use, and many achieved normal levels of daytime sleepiness in ≤2 months of starting ON-SXB. Support (if any) Avadel Pharmaceuticals

Abstract Introduction Sodium oxybate is strongly recommended by the American Academy of Sleep Medicine for the treatment of narcolepsy, a chronic sleep disorder characterized by excessive daytime sleepiness (EDS). This study was conducted to characterize demographic characteristics and concomitant medication use of patients with narcolepsy treated or not treated with oxybates (OXB). Methods An electronic health record–based search identified first-time patients from Mayo Clinic and Duke Health between 2002-2024 and 2012-2024, respectively. Patients had ≥1 narcolepsy-specific ICD-9/10 code and ≥1 diagnostic mention of narcolepsy in clinical notes (via natural language processing algorithm). Patients from both Mayo Clinic and Duke Health who were or were not treated with OXB were identified. Data were analyzed descriptively. Results Of 4722 patients, 654 (Mayo Clinic, n=378; Duke Health, n=276) received OXB, and 4068 (Mayo Clinic, n=2800; Duke Health, n=1268) received non-OXB treatments. The majority of patients were white (OXB-treated: 92.1%, 73.6%; non–OXB-treated: 91.1%, 69.2%) and female (OXB-treated: 68.3%, 76.8%; non–OXB-treated: 61.7%, 68.1%). Most OXB-treated patients (65.3%; 63.4%) had narcolepsy type 1 (NT1); the majority of non–OXB-treated patients (78.1%; 64.0%) had narcolepsy type 2 (NT2). The mean (SD) age of the OXB-treated cohort was younger than the non–OXB-treated cohort at the time of diagnosis (OXB-treated: 33.9 [15.3] years, 35.7 [13.2] years; non–OXB-treated: 45.5 [19.2] years, 42.5 [17.8] years). For both cohorts, the most common concomitant medications were stimulants (OXB-treated: 50.3%, 42.8%; non–OXB-treated: 41.8%, 35.2%). Conclusion In this retrospective analysis of nearly 5000 patients from Mayo Clinic and Duke Health, approximately 1 in 8 received OXB. While sodium oxybate has been approved for >2 decades and is strongly recommended for treatment of both EDS and cataplexy in narcolepsy, substantially greater OXB utilization was observed in patients with NT1. As both patients with NT1 and NT2 can experience other narcolepsy symptoms, further OXB-related education remains critical—particularly on the efficacy of sodium oxybate in the treatment of NT2. Support (if any) Avadel Pharmaceuticals

Abstract Introduction Once-nightly sodium oxybate (ON-SXB; LUMRYZ™) is approved to treat excessive daytime sleepiness (EDS) or cataplexy in patients ≥7 years of age with narcolepsy. Findings from 2 studies have demonstrated improvements in objective and subjective EDS with ON-SXB in patients with narcolepsy type 1 (NT1) or 2 (NT2) (NCT02720744, NCT06792708). To evaluate the effect of ON-SXB on EDS in a larger, more diverse narcolepsy patient population, changes in Epworth Sleepiness Scale (ESS) score were analyzed using specialty pharmacy data. Methods Demographic/clinical data were collected from Optum Frontier Therapies pharmacy for adults with NT1 or NT2 with ≥1 filled ON-SXB prescription, ≥1 ON-SXB clinical assessment, and ≥1 follow-up ESS score (6/1/2023-9/30/2024). ESS total scores were assessed at baseline and at each follow-up assessment after ON-SXB initiation. ESS assessment participation was voluntary. Data were analyzed descriptively and stratified by narcolepsy subtype. Results Of 452 patients identified, 195 had ≥1 follow-up ESS score and reported narcolepsy type (NT1, n=123 [63%; mean age, 38.6 years; female, 69%]; NT2, n=72 [37%; mean age, 40.7 years; female, 74%]). More patients with NT1 vs NT2 (72% vs 58%) had any prior oxybate use. Baseline concomitant stimulant/wake-promoting agent use was 58% and 64% for NT1 and NT2, respectively. Mean (SD) ESS total scores at baseline were 12.1 (5.7) and 12.2 (5.3) for patients with NT1 and NT2, respectively; 31% of NT1 and 33% of NT2 had severe EDS. For both subtypes, mean (SD) ESS scores were within the normal EDS range (≤10) by the first follow-up (median time, 52 days; NT1, 10.0 [5.5]; NT2, 9.6 [4.8]). At first follow-up, more than half of patients in the NT1 (55%) and NT2 (54%) subgroups achieved normal levels (ESS total score ≤10) of sleepiness, while 20% of NT1 patients and 10% of NT2 patients had severe EDS. Mean (SD) change from baseline in ESS score was -2.1 (4.3) and -2.6 (5.3) in the NT1 and NT2 subgroups, respectively. Conclusion In this real-world dataset, both NT1 and NT2 patients quickly experienced clinically meaningful improvements in ESS score after initiating ON-SXB. These results support ON-SXB as an effective EDS treatment, regardless of narcolepsy subtype. Support (if any) Avadel Pharmaceuticals

Abstract Introduction Narcolepsy is a rare, chronic sleep disorder associated with decreased quality of life and multiple comorbid conditions, including sleep-related and psychiatric or mood disorders. This study used aggregate electronic health record (EHR) data to characterize the demographics and comorbidities of patients with narcolepsy. Methods An EHR-based search identified first-time Duke Health patients between January 1, 2012, and March 31, 2024. Included patients had ≥1 narcolepsy-specific ICD-9 (347.*) and ICD-10 (G47.4*) codes and ≥1 disease-supportive statement in 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, number of diagnosis code instances, and mortality. Common comorbidities were compared and ranked between cohorts by odds ratio (OR). Statistical significance was determined using a chi-squared test; P values were corrected for multiple comparisons using Bonferroni correction. Results Within the EHR database of 2,617,188 patients, 1659 patients with a narcolepsy diagnosis were identified (mean age at first presentation, 32.4 years; white, 69%; female, 69%); the propensity-matched control cohort included 1659 patients (mean age at first presentation, 32.3 years; white, 69%; female, 69%). Comorbidities that occurred statistically significantly more frequently (all P< 0.0001) among the narcolepsy vs control cohort (OR [95% CI]) included sleep disorders: sleep-related movement disorders (26.26 [10.71-64.40]), hypersomnia (16.56 [12.54-21.87]), and circadian rhythm sleep disorders (15.43 [6.73-35.38]); psychiatric or mood disorders: posttraumatic stress disorder (3.08 [2.10-4.52]), attention deficit hyperactivity disorder (2.90 [2.28-3.68]), and depression (2.66 [2.27-3.11]); and pain disorders: trigeminal neuralgia (6.63 [2.80-15.70]), fibromyalgia (5.30 [3.58-7.85]), and chronic pain syndrome (3.37 [2.46-4.61]). Postural orthostatic tachycardia syndrome occurred statistically significantly more frequently (P< 0.0001) in the narcolepsy vs control cohort (7.24 [3.59-14.61]). Conclusion Consistent with prior EHR research, sleep, psychiatric, mood, and pain disorders were among the most frequently reported comorbidities of patients with narcolepsy. The results of this analysis of real-world demographic and clinical information of patients with narcolepsy may further inform clinicians of the most relevant concomitant disease states to consider when evaluating potential therapies. Support (if any) Avadel Pharmaceuticals

Abstract Introduction Once-nightly sodium oxybate (ON-SXB [LUMRYZ™]) is approved to treat excessive daytime sleepiness (EDS) or cataplexy in patients ≥7 years of age with narcolepsy. Real-world demographic/clinical characteristics and treatment adherence in patients with narcolepsy who received ON-SXB from a specialty pharmacy were assessed. Methods Baseline demographic/clinical data were collected from Optum Frontier Therapies pharmacy for patients with ≥1 filled ON-SXB prescription, ≥1 ON-SXB-related clinical assessment, and baseline Epworth Sleepiness Scale (ESS) score from 6/1/2023-9/30/2024. Adherence (≥80% of days covered) was assessed for patients with ≥3 months of ON-SXB use. Data were stratified by narcolepsy subtype (narcolepsy type 1 [NT1] and 2 [NT2] when available) and prior oxybate use (transitioned from prior oxybate therapy to ON-SXB ≤30 days of index [switch]/were oxybate-naive or discontinued oxybate >30 days before index [not-on-oxybate]). Data were analyzed descriptively. Results 452 patients were identified (NT1, 55%; NT2, 37%; NT unknown, 9%; switch, 40%; not-on-oxybate, 60% [oxybate-naive, n=147/271]). Mean (range) age was 38.9 (16.0-88.0) years. Most patients were female (68%) and had commercial insurance (78%). Overall, 67% of patients had prior oxybate use (NT1, 72% [n=179/247]; NT2, 59% [n=98/166]; switch, 100%; not-on-oxybate, 46% [n=124/271]); for these patients, the most common oxybate (65%) was mixed-salt oxybates (NT1, 61%; NT2, 70%; switch, 61%; not-on-oxybate, 70%). Overall, 64% of patients used stimulants/wake-promoting agents (WPAs) (NT1, 64%; NT2, 65%; switch, 60%; not-on-oxybate, 67%). Overall, the mean (SD) baseline ESS score was 12.0 ([5.5]; NT1, 11.7 [5.5]; NT2, 12.5 [5.3]; switch, 11.0 [5.7]; not-on-oxybate, 12.7 [5.3]). At baseline, 29% of patients experienced severe EDS (ESS score ≥16: NT1, 26%; NT2, 30%; switch, 20%; not-on-oxybate, 34%). Of 269 patients with ON-SXB use ≥3 months, 84% (NT1, 84%; NT2, 89%; switch, 94%; not-on-oxybate, 76%) demonstrated adherence. Conclusion Patients not on an oxybate had the highest baseline ESS scores and proportion with severe EDS, despite greater stimulant/WPA utilization. Patients with NT1 used oxybates more frequently than those with NT2 despite those with NT2 having higher baseline ESS scores and a greater proportion having severe EDS, suggesting oxybates merit earlier consideration in patients with NT2. Most patients demonstrated ON-SXB adherence, indicating they would likely receive full therapeutic benefit. Support (if any) Avadel Pharmaceuticals

Abstract Study Objectives Narcolepsy has a complex phenotype owing to differences in symptomatology, disease severity, and comorbidities. This is the first study to use aggregate electronic health record (EHR) data and natural language processing (NLP) algorithms to characterize the demographics and comorbidities of a large cohort of patients with narcolepsy. Methods First-time Mayo Clinic patients (2000–2020) who had ≥1 narcolepsy-specific ICD-9/10 code and ≥1 disease-supportive statement in the clinical notes (identified using an NLP algorithm) were identified. 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. Results In the EHR database (N = 6 389 186 patients), 2057 patients with narcolepsy were identified (median age, 32 years; 59.6% female; 92.6% white; and 89.2% non-Hispanic) and propensity matched with a control cohort. Among the top 20 comorbidities occurring more frequently in the narcolepsy cohort compared with the control cohort (odds ratio [OR], 1.67–3.94; p < .001]) were sleep disorders (restless legs syndrome, obstructive sleep apnea, and insomnia), mood disorders (depression, dysthymia, and anxiety), and pain disorders (chronic pain syndrome, migraine, fibromyalgia, carpal tunnel syndrome, and myalgia). Other comorbidities significantly associated with narcolepsy (OR, 1.33–1.95) were irritable bowel syndrome (p < .001), asthma (p < .001), cervical spondylosis (p < .01), syncope (p < .01), and hypothyroidism (p < .05). Conclusions This propensity-matched cohort study demonstrates increased psychiatric, sleep, and pain disorders in patients living with narcolepsy and challenges beyond narcolepsy-specific symptoms in this population. Understanding common narcolepsy-associated comorbidities may assist in tailoring treatment modalities.

Abstract Introduction To further characterize the many struggles and unmet needs of people with narcolepsy (PWN), passive social listening was used to explore how PWN describe the condition using their own words. Methods MyNarcolepsyTeam is a social network where members can organically share their experiences living with narcolepsy with one another. Following an online survey, organic posts, comments, questions, and answers posted from January 2022 to present were analyzed. Results Of 110 survey respondents, 31% reported that the time from symptom onset to diagnosis was ≥10 years. Social listening highlighted both misdiagnoses (eg, depression) and “missed” diagnoses (eg, sleep apnea but not narcolepsy). Almost half (43%) of respondents reported pain as a comorbidity. Social listening revealed the burden of painful comorbidities (eg, fibromyalgia, migraines, neuropathy), which often lead to additional medications and further sleep disruption. While 90% of respondents reported excessive daytime sleepiness, 81% also reported sleep disturbances. Nighttime disruptions experienced by PWN included poor sleep quality, vivid dreams, frequent awakenings, sleep paralysis, and abnormal REM cycles. Structured routines helped improve sleep for some PWN. Additionally, 33% of respondents reporting cataplexy always experienced full body cataplexy; 21% always experienced localized cataplexy; 43% experienced a mix of both, with the remaining answering ‘not sure.’ Social listening highlighted the dangers of cataplexy, including falls/fractures. Organic conversations also brought to bear the full range of emotions that can trigger an attack – from laughter, to being startled, to feeling stressed. In total, 65% of respondents were taking ≥2 medications to treat daytime and/or nighttime narcolepsy symptoms. Organic conversations highlighted the challenges PWN experience managing complex treatment regimens in an attempt to cope with the full spectrum of narcolepsy symptoms. Conclusion Insight into how narcolepsy is experienced in patients’ own words and how patients try to mitigate their symptoms will help sleep specialists better understand the challenges and needs of PWN, which can lead to both faster diagnosis and more effective, individualized treatment. Support (if any) Avadel Pharmaceuticals

Abstract Introduction Research was undertaken to better understand the path to a narcolepsy diagnosis, common symptoms, and the impact of narcolepsy on work, social interactions, and mental health. Methods In February 2022, an email invitation to an online, 27-question survey was sent to US members of MyNarcolepsyTeam, a social network of >9,800 members. Results In total, 110 members completed the survey. 38% of respondents started to experience symptoms before reaching 16 years of age. Most commonly experienced symptoms included excessive daytime sleepiness (EDS; 93%) and fatigue (84%). In total, 72% were also experiencing some form of sleep disturbance and 67% were already suffering from cognitive/memory challenges. 68% who were eventually diagnosed with narcolepsy type 1 (NT1) had cataplexy attacks. For 31%, getting to a narcolepsy diagnosis took ≥10 years. In fact, 64% were initially under- or misdiagnosed with something other than narcolepsy, including depression (73%), sleep apnea (36%), or attention-deficit/hyperactivity disorder (16%). 74% of patients with NT1 have continued to experience cataplexy, with 46% having some form of a cataplexy episode a few times per week. Cataplexy episodes were triggered by a wide range of emotional situations, including over-tiredness (70%), anger (48%), being startled (46%), laughter (46%), fear (44%), excitement (38%), or crying (33%). 76% of respondents indicated that the impact of narcolepsy on daily life is extremely or very severe. The far-reaching impact on quality of life was evident in that most respondents reported that narcolepsy interfered with work (82%), social life (86%), everyday chores (85%), and exercise (85%) and has limited career options (76%). The emotional toll of narcolepsy manifested in feeling isolated (83%), depressed (81%), anxious (80%), or embarrassed (75%). Conclusion Patients routinely experienced a misdiagnosis or a “missed” diagnosis based on common symptoms experienced. Being able to quickly identify narcolepsy as the root cause for symptoms of EDS, fatigue, and sleep disturbances can lead to getting the patient on the best treatment path as early as possible. Understanding the physical, emotional, and quality-of-life impact of narcolepsy can help clinicians provide a more holistic approach to treating their patients. Support (if any) Avadel Pharmaceuticals

Abstract Introduction Narcolepsy is a chronic sleep disorder with multiple comorbid conditions. Sodium oxybate (SXB) is strongly recommended for treatment of narcolepsy. This study used aggregate electronic health record (EHR) data to characterize demographic characteristics and comorbidities of patients with narcolepsy treated with or without SXB. Methods An EHR-based search identified first-time Mayo Clinic patients between 1975–2020. Patients had ≥1 narcolepsy-specific ICD-9/-10 code and ≥1 diagnostic mention of narcolepsy in clinical notes (natural-language-processing algorithm). Patients with narcolepsy treated with SXB were age/sex matched with a cohort without SXB treatment. Common comorbidities were identified using ICD-9/-10 codes and compared between cohorts (odds ratio [OR]). Results Of 4387 patients identified, 8% received SXB treatment (n=351; mean [IQR] age at first diagnosis code observed at Mayo Clinic, 32 [23.2-46.1] y; 65.5% female; 92.3% white); 4036 patients had no SXB treatment (mean [IQR] age at first diagnosis code observed at Mayo Clinic, 44.8 [29.8-59.0] y; 58.0% female; 88.9% white). The 10 most commonly reported comorbidities (overall population) were insomnia (46.6%), fatigue (46.3%), depression (42.2%), hypertension (36.2%), hyperlipidemia (34.2%), obstructive sleep apnea (32.3%), diabetes mellitus (31.3%), arrhythmia (27.3%), idiopathic hypersomnia (IH; 26.8%), and coronary artery disease (17.6%). A cohort of 351 patients without SXB were age/sex matched to patients with SXB for comparison of comorbidities. In the unadjusted analysis, P values were significant for differences between cohorts (OR [95% CI] SXB vs no SXB) for fatigue (0.72 [0.54-0.97]; P< 0.05; adjusted P>0.9) and IH (0.60 [0.43-0.84]; P< 0.01; adjusted P=0.29). After P value adjustment (Bonferroni correction), there were no significant differences between these cohorts in ORs for any comorbidity. The matched cohorts, which were younger than the overall population, had numerically lower rates of these diagnoses vs the overall population, except fatigue and IH in patients without SXB and depression in patients with SXB. Conclusion Among age-/gender-matched cohorts of patients with/ without SXB, there were no significant differences in comorbidities. Prevalence of comorbid IH/narcolepsy diagnoses highlight the diagnostic challenge in differentiating IH from narcolepsy type 2. SXB is highly effective but used by < 1:10 patients with narcolepsy in the Mayo Clinic health system. Support (if any) Avadel Pharmaceuticals