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Abstract Details

The First Light: Efficacy and Safety of a Multi-dose Study of Oveporexton (TAK-861), an Oral Orexin Receptor Two Agonist for the Treatment of Narcolepsy Type One
Sleep
S3 - Research Advances in Sleep and Clinical Impact (2:48 PM-3:00 PM)
010

To evaluate efficacy and safety of oveporexton (TAK-861), an oral orexin receptor 2 (OX2R)-selective agonist, in narcolepsy type 1 (NT1).

NT1, caused by loss of orexin-producing neurons in the hypothalamus, is characterized by excessive daytime sleepiness, cataplexy, disrupted nighttime sleep, sleep paralysis, and hypnagogic/hypnopompic hallucinations.
This double-blind, phase 3 study included participants aged 16–70 years across Europe, Japan, and North America with a confirmed diagnosis of NT1. Participants were randomized 3:3:2 to twice-daily oral oveporexton 1 mg, 2 mg, or placebo ≥3 hours apart for 12 weeks. The primary endpoint was change from baseline to week 12 in mean sleep latency on the Maintenance of Wakefulness Test (MWT). Secondary endpoints included change from baseline in ESS total score to week 12, weekly cataplexy rate (WCR) at week 12, and treatment-emergent adverse events (TEAEs).
168 participants (98 [58.3%] female, mean age 31.4 years) were randomized to oveporexton 1mg/1mg (n=61), 2mg/2mg (n=66), or placebo (n=41). At baseline, mean ESS score was 18.5, and MWT sleep latency was 5.0 minutes; median WCR was 26.0 attacks/week. At week 12, least square (LS) mean (95% CI) changes from baseline were statistically significant with oveporexton 1mg/1mg and 2mg/2mg for MWT sleep latency (13.83 [10.23, 17.44] and 17.20 [13.66, 20.73] minutes vs placebo, respectively; both P<0.001), and ESS total score (-8.00 [-9.87, -6.13] and -9.75 [-11.59, -7.90] vs placebo; both P<0.001). Incidence rate ratios of WCR for oveporexton were 0.34 (1mg/1mg) and 0.38 (2mg/2mg; both P<0.001 vs placebo). Overall, 88.1% of oveporexton-treated participants (111/126) experienced ≥1 TEAEs versus 53.7% (22/41) with placebo. The most common TEAEs were pollakiuria and insomnia; there were no treatment-related serious TEAEs. Of 157 participants who completed study treatment, 150 (95.5%) enrolled into the long-term extension. 

Oveporexton significantly improved measures of sleepiness and cataplexy frequency vs placebo and was generally well tolerated.
Authors/Disclosures
Giuseppe Plazzi, MD (University di Bologna)
PRESENTER 		The institution of Dr. Plazzi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TAKEDA. The institution of Dr. Plazzi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BIOPROJET. The institution of Dr. Plazzi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for JAZZ. The institution of Dr. Plazzi has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for OREXIA. The institution of Dr. Plazzi has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for OREXIA/CENTESSA.
Emmanuel Mignot, MD, PhD (Stanford University) Dr. Mignot has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Takeda. Dr. Mignot has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Jazz Pharmaceutical. Dr. Mignot has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai Pharmaceuticals, Inc. . Dr. Mignot has received personal compensation in the range of $0-$499 for serving as a Consultant for EcoR1. Dr. Mignot has received personal compensation in the range of $0-$499 for serving as a Consultant for ApneaCo. Dr. Mignot has received personal compensation in the range of $0-$499 for serving as a Consultant for Eisai Pharmaceuticals. Dr. Mignot has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Centessa .
Isabelle Arnulf, MD (Hopital Pitie-Salpetriere) Dr. Arnulf has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ONO Pharma. Dr. Arnulf has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ROCHE pharma. Dr. Arnulf has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for IDORSIA Pharma. Dr. Arnulf has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for UCB Pharma. The institution of Dr. Arnulf has received research support from BIOPROJET pharma. The institution of Dr. Arnulf has received research support from VITALAIRE. The institution of Dr. Arnulf has received research support from French SLEEP Socity (SFRMS). The institution of Dr. Arnulf has received research support from Paris Brain Insitute. Dr. Arnulf has a non-compensated relationship as a scientific advisory with Jazz Pharma that is relevant to AAN interests or activities. Dr. Arnulf has a non-compensated relationship as a scientific advisory with Theranexus that is relevant to AAN interests or activities.
Rafael V. Del Río Villegas, MD, PhD Dr. Del Río Villegas has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TAKEDA. Dr. Del Río Villegas has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ALKERMES.
Ramin Khatami, MD Dr. Khatami has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Takeda Pharmaceuticals International AG. Dr. Khatami has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Idorsia. Dr. Khatami has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Idorsia. Dr. Khatami has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Takeda Pharmaceuticals International AG. Dr. Khatami has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Idorsia. Dr. Khatami has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Takeda Pharmaceuticals International AG. Dr. Khatami has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Swiss Insurance Medicine.
Gerrit J. Lammers, MD (LUMC) The institution of Dr. Lammers has received research support from Takeda.
Mitsutaka Taniguchi, MD Dr. Taniguchi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Takeda Pharmaceutical Company Limited. Dr. Taniguchi has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Eisai Co., Ltd.. Dr. Taniguchi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eisai Co., Ltd.. Dr. Taniguchi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eisai Co., Ltd.. An immediate family member of Dr. Taniguchi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Teijin Pharma Limited. Dr. Taniguchi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Teijin Pharma Limited. Dr. Taniguchi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Teijin Pharma Limited. Dr. Taniguchi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alfresa Pharma Corporation. Dr. Taniguchi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alfresa Pharma Corporation.
Harisha Kadali, MBBS Dr. Kadali has received personal compensation for serving as an employee of Takeda Pharmaceuticals. Dr. Kadali has stock in Takeda Pharmaceuticals.
Yeting Du (Takeda) Yeting Du has received personal compensation for serving as an employee of Takeda Pharmaceuticals.
Samuel Hsiao, PhD Dr. Hsiao has received personal compensation for serving as an employee of Takeda. Dr. Hsiao has stock in Takeda.
Tina Olsson, PhD Dr. Olsson has received personal compensation for serving as an employee of Takeda. Dr. Olsson has stock in Takeda.
Sarah I. Sheikh, BM Bch, MSc, MRCP, FAAN Dr. Sheikh has received personal compensation for serving as an employee of Takeda.
Christian Von Hehn No disclosure on file
Mark R. Etherton, MD (Massachusetts General Hospital) Dr. Etherton has received personal compensation for serving as an employee of Takeda Pharmaceutical Company. Dr. Etherton has received personal compensation in the range of $50,000-$99,999 for serving as an officer or member of the Board of Directors for Argenica Therapeutics.
Yves Dauvilliers, MD, PhD (Hopital Gui De Chaulliac) Yves Dauvilliers, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for idorsia. Yves Dauvilliers, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for JAZZ. Yves Dauvilliers, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Takeda. Yves Dauvilliers, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Avadel. Yves Dauvilliers, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alkermes. Yves Dauvilliers, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Centessa. Yves Dauvilliers, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bioprojet. Yves Dauvilliers, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Harmony Bioscience.