Abstract Details

Title ENCORE: Topline Results of a Phase Three Open-label Extension and Randomized-withdrawal Trial of AXS-12 in Narcolepsy

Topic Sleep

Presentation(s) P6 - Poster Session 6 (5:00 PM-6:00 PM)

Poster/Presentation
Number 14-006

Objective The ENCORE study evaluated long-term efficacy and safety of AXS-12 (reboxetine) in participants with narcolepsy type 1 (NT1) who completed the Phase 3 SYMPHONY study.

Background AXS-12 is a highly selective norepinephrine reuptake inhibitor and cortical dopamine modulator under development for narcolepsy. In the Phase 3 SYMPHONY study, AXS-12 met the primary endpoint, significantly reducing weekly cataplexy attack frequency versus placebo.

Design/Methods ENCORE included a 24-week open-label period (OLP) of continued AXS-12 treatment, and a 3-week double-blind, randomized withdrawal period (DBRWP) during which participants were randomized to continue AXS-12 or switch to placebo. The primary endpoint was change from randomization in weekly cataplexy attack frequency versus placebo at DBRWP week 3.

Results ENCORE enrolled 68 participants; 42 completed the OLP and entered the DBRWP (AXS-12, n=22; placebo, n=20). In SYMPHONY, baseline median weekly cataplexy attack frequency was 19.9 pretreatment. At DBRWP randomization in ENCORE, mean weekly cataplexy attack frequency was 4.2 (AXS-12) and 6.9 (placebo). Participants randomized to placebo experienced a mean increase of 10.29 weekly cataplexy attacks versus 1.32 for AXS-12 at DBRWP end (p=0.017). At OLP month 1 and 6, cataplexy response (≥50% reduction) was achieved by 72% and 82%, and cataplexy-free days increased from 14% to 61% and 70%. OLP adverse events (AEs; ≥5%) were nausea and tachycardia (both 5.9%); no new safety signals were detected. Discontinuations due to AEs occurred in 17.6% of participants in the OLP.

Conclusions AXS-12 was well-tolerated and demonstrated maintenance of efficacy with long-term open-label use. Switching to placebo resulted in significant worsening of cataplexy attack frequency relative to continued AXS-12 treatment. These results support the therapeutic impact of AXS-12 for narcolepsy.

Authors/Disclosures
Richard K. Bogan, MD (SleepMed) PRESENTER	Dr. Bogan has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Jazz Pharmaceutical . Dr. Bogan has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Takeda. Dr. Bogan has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Axsome . Dr. Bogan has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Harmony. Dr. Bogan has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Jazz. Dr. Bogan has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Axsome. Dr. Bogan has received personal compensation in the range of $50,000-$99,999 for serving as an Expert Witness for Jazz. The institution of Dr. Bogan has received research support from Jazz Pharmaceuticals. The institution of Dr. Bogan has received research support from Harmony . The institution of Dr. Bogan has received research support from Eisai. The institution of Dr. Bogan has received research support from Avadel. The institution of Dr. Bogan has received research support from Takeda. The institution of Dr. Bogan has received research support from Suven. The institution of Dr. Bogan has received research support from Axsome. The institution of Dr. Bogan has received research support from Merck. The institution of Dr. Bogan has received research support from Liva Nova. The institution of Dr. Bogan has received research support from Nyxoah. Dr. Bogan has received research support from Bayer. Dr. Bogan has received intellectual property interests from a discovery or technology relating to health care.
Michael J. Thorpy, MD (Montefiore Medical Center)	Dr. Thorpy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Jazz. Dr. Thorpy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avadel. Dr. Thorpy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for alkermes. Dr. Thorpy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Harmony. Dr. Thorpy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for centessa. Dr. Thorpy has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Axsome. Dr. Thorpy has received publishing royalties from a publication relating to health care.
Lois Krahn	Lois Krahn has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avadel. Lois Krahn has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Takeda. Lois Krahn has received personal compensation in the range of $500-$4,999 for serving as an officer or member of the Board of Directors for Arizona Medical Board. The institution of Lois Krahn has received research support from Takeda. Lois Krahn has received publishing royalties from a publication relating to health care.
Bruce C. Corser, MD	Dr. Corser has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Axsome. Dr. Corser has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Avadel. The institution of Dr. Corser has received research support from Alkermes, . The institution of Dr. Corser has received research support from Apnimed. The institution of Dr. Corser has received research support from Avadel. The institution of Dr. Corser has received research support from Axsome. The institution of Dr. Corser has received research support from Eisai. The institution of Dr. Corser has received research support from Eli Lilly. The institution of Dr. Corser has received research support from Harmony. The institution of Dr. Corser has received research support from Incannex. The institution of Dr. Corser has received research support from Jazz. The institution of Dr. Corser has received research support from Mineralys. The institution of Dr. Corser has received research support from Suven. The institution of Dr. Corser has received research support from Takeda. The institution of Dr. Corser has received research support from Centessa.
Colin Shapiro	Colin Shapiro has nothing to disclose.
Shirley Chen, BS	Ms. Chen has nothing to disclose.
Angad Chhabra	Angad Chhabra has nothing to disclose.
Eileen Leary, PhD (Axsome Therapeutics)	Dr. Leary has received personal compensation for serving as an employee of Centessa Pharmaceuticals. Dr. Leary has received personal compensation for serving as an employee of Axsome Therapeutics. Dr. Leary has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Clinical Partners Group. Dr. Leary has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pulse Infoframe. Dr. Leary has or had stock in Jazz Pharmaceuticals.Dr. Leary has or had stock in Axsome Therapeutics.Dr. Leary has or had stock in Centessa Pharmaceuticals.
Herriot Tabuteau (Axsome Therapeutics)	Herriot Tabuteau has received personal compensation in the range of $100,000-$499,999 for serving as an officer or member of the Board of Directors for Axsome Therapeutics.

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