Core Insights - Harmony Biosciences Holdings, Inc. (HRMY) shares fell by 16.56% on September 24 following the announcement of the failure of the late-stage RECONNECT study for ZYN002 in Fragile X syndrome (FXS) [1][2] - The RECONNECT study was a randomized, double-blind, placebo-controlled trial aimed at assessing the efficacy and safety of ZYN002, a transdermal gel cannabidiol for patients aged 3 to under 30 years with FXS [1][2] - The study did not meet its primary endpoint of improving social avoidance, attributed to a higher-than-expected placebo response rate [2] Company Performance - Year-to-date, HRMY has experienced a 22.2% decline, contrasting with a 5.3% gain in the industry [3] - The company's lead drug, Wakix (pitolisant), generated revenues of $200.5 million in the second quarter [5][7] - HRMY plans to initiate phase III registrational trials for a high dose of pitolisant in narcolepsy and idiopathic hypersomnia in the fourth quarter of 2025 [5][7] Pipeline Expansion - HRMY has broadened its pipeline into rare epilepsy through the acquisition of Epygenix Therapeutics, adding EPX-100 and EPX-200 to its portfolio [6][7] - EPX-100 is currently in phase III registrational trials for Dravet Syndrome and Lennox-Gastaut Syndrome, while EPX-200 is in the pre-IND phase for developmental and epileptic encephalopathies [6]

Core Insights - Jazz Pharmaceuticals presented new real-world evidence and Phase 4 data at World Sleep 2025 and the Psych Congress, highlighting the effectiveness of Xywav in treating narcolepsy and idiopathic hypersomnia [1][2][6] Group 1: Clinical Trial Results - The Phase 4 DUET trial demonstrated that low-sodium Xywav significantly improves daytime and nighttime symptoms in adults with narcolepsy or idiopathic hypersomnia [1][6] - Participants in the DUET trial experienced fewer awakenings and improved sleep measures, indicating enhanced sleep quality [6] - The analysis of the DUET data showed reduced sleep inertia and improved alertness among participants receiving optimized Xywav treatment [6] Group 2: Real-World Evidence - Real-world analyses indicated that individuals with narcolepsy or idiopathic hypersomnia face elevated risks of cardiovascular and cardiometabolic conditions, emphasizing the need for sodium intake reduction [6][8] - The data presented at the congresses reinforce the importance of understanding treatment impacts on both daytime and nighttime symptoms for patients [2][6] Group 3: Xywav Overview - Xywav is the only low-sodium oxybate approved by the FDA for treating cataplexy and excessive daytime sleepiness in patients aged 7 and older with narcolepsy [11] - It is also the first FDA-approved treatment for idiopathic hypersomnia in adults, addressing multiple symptoms including excessive daytime sleepiness and sleep inertia [12] - Xywav has a significantly lower sodium content compared to other oxybate therapies, providing a safer option for patients sensitive to sodium intake [11][12] Group 4: Company Positioning - Jazz Pharmaceuticals aims to leverage both Phase 4 clinical trials and real-world evidence to enhance understanding of sleep disorders and improve treatment outcomes [2][40] - The company is dedicated to developing innovative therapies for serious diseases, with a focus on sleep disorders and oncology [40][41]