Lois Krahn’s research while affiliated with Mayo Clinic and other places

Once-nightly sodium oxybate (LUMRYZ™; ON-SXB; FT218) significantly improved narcolepsy symptoms in the phase 3 REST-ON trial. The objective of this post hoc analysis was to investigate the early efficacy of ON-SXB at weeks 1 (4.5-g dose) and 2 (6-g dose). In REST-ON, participants (≥ 16 years) with narcolepsy type 1 or 2 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. Protocol-prespecified efficacy assessments were conducted at weeks 3 (6-g dose), 8 (7.5-g dose), and 13 (9-g dose). A post hoc analysis was conducted to assess the early efficacy of ON-SXB, defined as efficacy at weeks 1 (4.5-g dose) and 2 (6-g dose) on Epworth Sleepiness Scale (ESS) score, visual analog scale (VAS) sleep quality, and VAS refreshing nature of sleep. Least squares mean differences (LSMD) in change from baseline to weeks 1 and 2, 95% confidence intervals (CIs), and P values were calculated using mixed-effects models for repeated measures. In the modified intent-to-treat population (n = 190; ON-SXB, n = 97; placebo, n = 93), baseline ESS scores were 16.6 and 17.5, sleep quality scores were 53.8 and 55.9, and refreshing nature of sleep scores were 46.5 and 49.9 with ON-SXB and placebo, respectively. At week 1 (4.5 g), numerical improvement in ESS score (LSMD [95% CI], − 0.7 [− 1.6 to 0.2]) and significant improvements in sleep quality (3.6 [1.1–6.1]; P < 0.01) and refreshing nature of sleep (3.2 [0.5–5.9]; P < 0.05) were observed with ON-SXB versus placebo. At week 2 (6 g), significant improvements with ON-SXB versus placebo were observed for ESS score (− 1.3 [− 2.4 to − 0.2]; P < 0.02), sleep quality (7.0 [3.8–10.1]; P < 0.001), and refreshing nature of sleep (5.8 [2.3–9.4]; P = 0.001). ON-SXB improved daytime sleepiness, sleep quality, and refreshing nature of sleep, with observable benefits beginning in the first week of treatment. These data may help clinicians set expectations with patients. NCT02720744.

Narcolepsy is a chronic, burdensome neurologic disorder that significantly impacts the daily life of people with narcolepsy (PWN). Real-world perspectives from PWN can help address their unique experiences and treatment needs. PWN were surveyed to examine the path to a narcolepsy diagnosis, the breadth of symptom burden experienced by PWN, and current trends in treatment. A 15-min online survey was sent by email to 3959 US members of MyNarcolepsyTeam (February 2022). The survey was divided into three sections (screening [patient characteristics], diagnosis/symptoms, and patient quality of life) for a total of 27 questions. In total, 110 members completed the survey. Of these, most were female (84%) and nearly half (48%) were diagnosed with narcolepsy type 1 (with cataplexy). Approximately one-third (31%) of members reported receiving a definitive diagnosis ≥ 10 years after first speaking with a clinician; most were previously diagnosed with depression (73%). Excessive daytime sleepiness (EDS, 93%) and fatigue (84%) were the most frequently reported symptoms that prompted respondents to seek a diagnosis or feel that something was wrong. Additionally, EDS was reported as the most troubling symptom (92%). Respondents’ most desired treatment outcome was to stop sleeping during the day (77%). Most (76%) indicated an extremely or very severe impact on daily life. One in eight respondents were not taking any medication for their narcolepsy. Of those taking medication, 58% received polypharmacy to address narcolepsy symptoms. These survey findings further characterize the diagnostic delay, symptom burden, and treatment needs of PWN. Understanding the breadth of impact of narcolepsy from the patients’ perspective could improve shared decision-making between PWN and their treating clinicians.

Introduction Patients with excessive daytime sleepiness (EDS) associated with narcolepsy or obstructive sleep apnea (OSA) struggle to maintain wakefulness. Solriamfetol (Sunosi®) is a dopamine/norepinephrine reuptake inhibitor with agonistic properties at TAAR1 and serotonin 1A receptors; it is approved to treat EDS associated with narcolepsy (75–150 mg/day) or OSA (37.5–150 mg/day). This post-hoc analysis characterized the effects of solriamfetol on the propensity of participants with EDS associated with narcolepsy or OSA to maintain wakefulness. Methods The safety and efficacy of solriamfetol has been evaluated in participants with EDS and narcolepsy or OSA in the phase 3 trials, TONES 2 and TONES 3. Participants were randomized to placebo or solriamfetol (37.5 mg [OSA only], 75 mg, 150 mg, or 300 mg) once daily for 12 weeks. This post-hoc analysis evaluated the proportion of participants who achieved improvement from baseline on various 40-minute Maintenance of Wakefulness Test (MWT) thresholds (≥5, ≥10, ≥15, and ≥20 minutes) and mean sleep latencies ≥30 and ≥40 minutes at weeks 1, 4, and 12. Comparisons between solriamfetol and placebo were evaluated using Fisher’s exact test. Results A greater proportion of participants with narcolepsy achieved improvement from baseline of ≥15 and ≥20 minutes on the MWT with solriamfetol 150 mg (36% and 18%, respectively) and 300 mg (38% and 28%) compared with placebo (4% and 4%) at week 12 (P≤0.028); findings were similar at week 12 in participants with OSA with solriamfetol 75 mg (28% and 13%), 150 mg (37% and 25%), and 300 mg (44% and 28%) compared with placebo (8% and 3%; P≤0.034). A greater proportion of participants with narcolepsy achieved MWT sleep latency ≥30 minutes at week 12 with solriamfetol 150 mg (24%) and 300 mg (30%) compared with placebo (2%; P≤0.002); results were similar in participants with OSA for MWT sleep latency ≥30 minutes at week 12 with solriamfetol 75 mg (28%), 150 mg (34%), and 300 mg (44%) compared with placebo (11%; P≤0.012). Conclusion These findings suggest solriamfetol leads to substantial improvements on objective propensity to stay awake in a large proportion of patients with narcolepsy or OSA when compared with placebo. Support (if any) Axsome Therapeutics, Jazz Pharmaceuticals

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