Alkermes Announces Positive Topline Results From Vibrance-1 Phase 2 Study of Once-Daily Alixorexton in Patients With Narcolepsy Type 1
Alkermes (NASDAQ:ALKS) announced positive topline results from its Vibrance-1 Phase 2 study of alixorexton in patients with narcolepsy type 1 (NT1). The study met its primary endpoint, demonstrating statistically significant improvements in wakefulness across all tested doses (4mg, 6mg, and 8mg) compared to placebo.
The once-daily oral treatment showed clinically meaningful improvements in multiple areas: normalized wakefulness (MWT), reduced excessive daytime sleepiness (ESS), and improved patient-reported outcomes related to disease severity, fatigue, and cognition. The drug was generally well-tolerated, with no serious adverse events reported. Over 95% of participants continued into the seven-week open-label extension.
Based on these positive results, Alkermes plans to advance alixorexton to Phase 3 development for NT1. Detailed results will be presented at the World Sleep Congress in September 2025.
Alkermes (NASDAQ:ALKS) ha annunciato risultati positivi preliminari dallo studio di Fase 2 Vibrance-1 sull'alixorexton in pazienti con narcolessia di tipo 1 (NT1). Lo studio ha raggiunto l'endpoint primario, mostrando miglioramenti statisticamente significativi nella vigilanza a tutte le dosi testate (4mg, 6mg e 8mg) rispetto al placebo.
Il trattamento orale una volta al giorno ha evidenziato miglioramenti clinicamente rilevanti in diversi ambiti: normalizzazione della vigilanza (MWT), riduzione della sonnolenza eccessiva diurna (ESS) e miglioramenti nei risultati riferiti dai pazienti riguardo alla gravità della malattia, affaticamento e capacità cognitive. Il farmaco è stato generalmente ben tollerato, senza eventi avversi gravi segnalati. Oltre il 95% dei partecipanti ha proseguito nella fase di estensione in aperto della durata di sette settimane.
Grazie a questi risultati positivi, Alkermes intende procedere con lo sviluppo di Fase 3 per l'alixorexton nella NT1. I risultati dettagliati saranno presentati al World Sleep Congress nel settembre 2025.
Alkermes (NASDAQ:ALKS) anunció resultados positivos preliminares de su estudio de Fase 2 Vibrance-1 sobre alixorexant en pacientes con narcolepsia tipo 1 (NT1). El estudio cumplió su objetivo principal, demostrando mejoras estadísticamente significativas en la vigilia en todas las dosis probadas (4mg, 6mg y 8mg) en comparación con el placebo.
El tratamiento oral de una vez al día mostró mejoras clínicamente significativas en varias áreas: normalización de la vigilia (MWT), reducción de la somnolencia excesiva diurna (ESS) y mejoras en los resultados reportados por los pacientes relacionados con la gravedad de la enfermedad, fatiga y cognición. El medicamento fue generalmente bien tolerado, sin eventos adversos graves reportados. Más del 95% de los participantes continuaron en la extensión abierta de siete semanas.
Con base en estos resultados positivos, Alkermes planea avanzar alixorexant a la Fase 3 para NT1. Los resultados detallados se presentarán en el Congreso Mundial del Sueño en septiembre de 2025.
Alkermes (NASDAQ:ALKS)는 기면증 1형(NT1) 환자를 대상으로 한 알릭소렉스톤의 Vibrance-1 2상 연구에서 긍정적인 초기 결과를 발표했습니다. 연구는 주요 평가변수를 충족했으며, 모든 투여 용량(4mg, 6mg, 8mg)에서 위약 대비 각각 통계적으로 유의미한 각성 개선을 보였습니다.
하루 한 번 경구 투여하는 이 치료법은 정상 각성(MWT), 과도한 주간 졸림(ESS) 감소, 질병 중증도, 피로 및 인지와 관련된 환자 보고 결과에서 임상적으로 의미 있는 개선을 나타냈습니다. 약물은 대체로 잘 견뎌졌으며, 심각한 부작용은 보고되지 않았습니다. 95% 이상의 참가자가 7주간의 공개 라벨 연장 연구에 계속 참여했습니다.
이러한 긍정적인 결과를 바탕으로 Alkermes는 NT1 치료를 위한 알릭소렉스톤 3상 개발을 진행할 계획입니다. 상세 결과는 2025년 9월 세계 수면 학술대회에서 발표될 예정입니다.
Alkermes (NASDAQ:ALKS) a annoncé des résultats positifs préliminaires de son étude de phase 2 Vibrance-1 portant sur l'alixorexant chez des patients atteints de narcolepsie de type 1 (NT1). L'étude a atteint son critère principal, démontrant des améliorations statistiquement significatives de la vigilance à toutes les doses testées (4 mg, 6 mg et 8 mg) par rapport au placebo.
Le traitement oral une fois par jour a montré des améliorations cliniquement significatives dans plusieurs domaines : vigilance normalisée (MWT), réduction de la somnolence diurne excessive (ESS) et amélioration des résultats rapportés par les patients concernant la sévérité de la maladie, la fatigue et les fonctions cognitives. Le médicament a été généralement bien toléré, sans événements indésirables graves signalés. Plus de 95 % des participants ont poursuivi dans l'extension ouverte de sept semaines.
Sur la base de ces résultats positifs, Alkermes prévoit de faire progresser l'alixorexant vers le développement de phase 3 pour la NT1. Les résultats détaillés seront présentés au Congrès mondial du sommeil en septembre 2025.
Alkermes (NASDAQ:ALKS) gab positive Zwischenergebnisse der Phase-2-Studie Vibrance-1 mit Alixorexton bei Patienten mit Narkolepsie Typ 1 (NT1) bekannt. Die Studie erreichte ihren primären Endpunkt und zeigte statistisch signifikante Verbesserungen der Wachheit bei allen getesteten Dosen (4 mg, 6 mg und 8 mg) im Vergleich zu Placebo.
Die einmal täglich oral verabreichte Behandlung zeigte klinisch relevante Verbesserungen in mehreren Bereichen: normalisierte Wachheit (MWT), verringerte übermäßige Tagesschläfrigkeit (ESS) und verbesserte patientenberichtete Ergebnisse bezüglich Krankheits-schwere, Müdigkeit und Kognition. Das Medikament wurde allgemein gut vertragen, es wurden keine schwerwiegenden Nebenwirkungen berichtet. Über 95 % der Teilnehmer setzten die Behandlung in der siebenwöchigen offenen Verlängerungsphase fort.
Aufgrund dieser positiven Ergebnisse plant Alkermes, Alixorexton für NT1 in die Phase-3-Entwicklung zu überführen. Detaillierte Ergebnisse werden auf dem World Sleep Congress im September 2025 vorgestellt.
- Met primary endpoint with statistically significant improvements in wakefulness across all doses (p<0.0001)
- Achieved normative wakefulness scores (mean sleep latency >20 minutes) across all dose groups
- Demonstrated clinically meaningful improvements in excessive daytime sleepiness, fatigue, and cognition
- High patient retention with >95% of participants continuing to open-label extension
- Generally well-tolerated with no serious adverse events reported
- Most treatment-emergent adverse events reported, though mild to moderate in severity
- Statistical significance for cataplexy improvement achieved only at 6mg dose (p=0.005)
Insights
Alkermes' alixorexton shows remarkable Phase 2 efficacy for narcolepsy type 1, with compelling safety profile supporting rapid Phase 3 advancement.
The Vibrance-1 Phase 2 results for alixorexton represent a significant clinical breakthrough in narcolepsy treatment. The data quality is particularly robust, showing dose-dependent improvements in wakefulness across all tested doses (4mg, 6mg, and 8mg) with high statistical significance (p<0.0001) on the primary endpoint Maintenance of Wakefulness Test (MWT).
Most impressively, alixorexton achieved normative wakefulness (mean sleep latency >20 minutes) across all dose groups, representing a clinically meaningful outcome that directly addresses the core symptom of narcolepsy. The consistent efficacy on the Epworth Sleepiness Scale (p<0.0001 at all doses) further validates these findings in a real-world context.
What truly distinguishes these results is the breadth of symptom improvement beyond just wakefulness. The drug demonstrated meaningful benefits on fatigue (PROMIS-Fatigue, p<0.01), cognitive function (BC-CCI, p<0.0001), and overall narcolepsy severity (NSS, p<0.001). This suggests alixorexton addresses multiple symptom domains that impact quality of life, potentially offering advantages over current treatments.
The safety profile appears highly favorable, with no serious adverse events reported and mostly mild-to-moderate side effects consistent with Phase 1 findings. The >95% continuation rate into the open-label extension speaks volumes about tolerability and perceived benefit.
Mechanistically, as an orexin 2 receptor agonist, alixorexton targets the underlying pathophysiology of narcolepsy type 1, which involves loss of orexin-producing neurons. This positions it as a potential disease-modifying therapy rather than merely symptomatic treatment.
– Alixorexton Demonstrated Clinically Meaningful and Statistically Significant Improvements in Wakefulness at All Doses Tested Compared to Placebo in Patients With Narcolepsy Type 1 –
– Alixorexton Demonstrated Robust and Consistent Improvements in Patient-Reported Outcomes Related to Disease Severity, Fatigue and Cognition at All Doses Tested –
– Alixorexton Was Generally Well Tolerated at All Doses Tested –
– Detailed Results to Be Presented at Upcoming World Sleep Congress –
– Data Support Advancement of Alixorexton to Phase 3 Development in Narcolepsy –
"These compelling results demonstrated that once-daily alixorexton normalized wakefulness and excessive daytime sleepiness scores in highly symptomatic patients with narcolepsy type 1 with a generally well tolerated profile across all doses tested. In addition, the initial data from patient-reported outcome measures related to fatigue and cognition are truly exciting and highlight the breadth of benefit that alixorexton may provide across multiple facets of narcolepsy. There is a clear and pressing need for new therapies for narcolepsy type 1, as patients continue to face a range of persistent symptoms that disrupt their day-to-day lives," said Giuseppe Plazzi, M.D., Ph.D., Neurologist, Director of the Narcolepsy Center at the IRCCS of the Neurological Sciences of Bologna and Professor of Childhood Neuropsychiatry at the University of Modena and
"Data from Vibrance-1 further characterize the clinical profile of alixorexton across a range of once-daily doses in a multiweek study in patients with narcolepsy type 1. Based on the positive outcomes across multiple symptoms important to patients, we are moving forward expeditiously to initiate a global phase 3 program. We look forward to sharing detailed data from Vibrance-1 at the World Sleep meeting in September," said Craig Hopkinson, M.D., Chief Medical Officer and Executive Vice President, Research & Development at Alkermes. "These positive topline data represent an important stride forward for the alixorexton development program and Alkermes' broader portfolio of orexin 2 receptor agonists. Alkermes is at the forefront of development in this exciting potential therapeutic category, and these data support our hypothesis that the therapeutic potential of orexin 2 receptor agonists extends beyond improvements in wakefulness to other symptoms such as fatigue and cognition in narcolepsy."
Vibrance-1 is a global, randomized, double-blind, placebo-controlled, multiple dose phase 2 study conducted in patients with NT1 (n=92). Patients were randomized (1:1:1:1) to receive a once-daily dose of alixorexton (4 mg, 6 mg or 8 mg) or placebo for six weeks.
Primary Endpoint
- Maintenance of Wakefulness Test (MWT): Across all doses tested, alixorexton demonstrated statistically significant, clinically meaningful and dose-dependent improvements from baseline in mean sleep latency compared to placebo at week six (p<0.0001 at all doses)1.
Key Secondary Endpoints
- Epworth Sleepiness Scale (ESS)2: At all doses tested, alixorexton drove statistically significant and clinically meaningful improvements from baseline in excessive daytime sleepiness compared to placebo on the Epworth Sleepiness Scale at week six (p<0.0001 at all doses).
- Weekly Cataplexy Rates (WCR): Alixorexton numerically improved weekly cataplexy rates across all doses compared to placebo at week six and achieved statistical significance at the 6 mg dose (p=0.005).
Exploratory Patient-Reported Outcome Measures
Alixorexton demonstrated consistent and clinically meaningful improvements across a number of patient-reported outcome measures of symptoms important to patients including, but not limited to, the following (reported p-values are nominal):
- Narcolepsy Severity Scale (NSS)3: Across all doses tested, alixorexton demonstrated clinically meaningful improvements from baseline in narcolepsy symptom severity as compared to placebo at week six (p<0.001 at all doses).
- British Columbia Cognitive Complaints Inventory (BC-CCI)4: Across all doses tested, alixorexton demonstrated clinically meaningful improvements from baseline in cognitive complaints compared to placebo at week six (p<0.0001 at all doses).
- PROMIS (Patient-Reported Outcomes Measurement Information System)-Fatigue5: Across all doses tested, alixorexton demonstrated clinically meaningful improvements from baseline in fatigue as compared to placebo at week six (p<0.01 at all doses).
Alixorexton was generally well tolerated across all doses tested in the randomized double-blind period of the Vibrance-1 study. No treatment-emergent serious adverse events were reported. Most treatment-emergent adverse events (TEAEs) were mild to moderate in severity and were generally consistent with the events observed across the alixorexton phase 1 program in healthy volunteers and patients with NT1, NT2 and IH. There were no treatment-related safety signals observed in hepatic and renal parameters, vital signs, or ophthalmic exams. More than
Alkermes plans to present detailed safety and efficacy results from the Vibrance-1 phase 2 study in an oral presentation at the upcoming World Sleep Congress, taking place Sept. 5-10, 2025 in
About the Vibrance-1 Phase 2 Study (NCT06358950)
Vibrance-1 is a phase 2, randomized, double-blind, dose-range-finding, placebo-controlled study evaluating the safety and efficacy of alixorexton (formerly referred to as ALKS 2680) in adults with narcolepsy type 1 (NT1). Participants (n=92) were randomized to receive one of three doses of alixorexton (4 mg, 6 mg or 8 mg) or placebo to be taken once-daily for six weeks. The primary endpoint assessed whether participants taking alixorexton experienced an improvement in wakefulness compared to participants taking placebo, as measured by the change from baseline in mean sleep latency on the maintenance of wakefulness test (MWT) at week six. Secondary endpoints included change from baseline in Epworth Sleepiness Scale (ESS) score and mean weekly cataplexy rate (WCR) at week six, and incidence of adverse events. The study also included a number of patient-reported outcome measures, which evaluated the effect of alixorexton on participants' disease severity, fatigue and cognition. All participants in the double-blind portion of the study were eligible to continue to a seven-week open-label safety extension portion of the study, followed by a long-term safety study.
About Alixorexton
Alixorexton (formerly referred to as ALKS 2680) is a novel, investigational, oral, selective orexin 2 receptor (OX2R) agonist in development as a once-daily treatment for narcolepsy type 1 (NT1), narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH). Orexin, a neuropeptide produced in the lateral hypothalamus, is considered to be the master regulator of wakefulness due to its activation of multiple, downstream wake-promoting pathways that project widely throughout the brain.6 Targeting the orexin system may address excessive daytime sleepiness across hypersomnolence disorders, whether or not deficient orexin signaling is the underlying cause of disease.7 Once-daily oral administration of alixorexton was previously evaluated in a phase 1 study in healthy volunteers and patients with NT1, NT2 and IH, and is currently being evaluated in the phase 2 Vibrance-1, Vibrance-2 and Vibrance-3 studies in patients with NT1, NT2 and IH, respectively.
About Alkermes plc
Alkermes plc is a global biopharmaceutical company that seeks to develop innovative medicines in the field of neuroscience. The company has a portfolio of proprietary commercial products for the treatment of alcohol dependence, opioid dependence, schizophrenia and bipolar I disorder, and a pipeline of clinical and preclinical candidates in development for neurological disorders, including narcolepsy and idiopathic hypersomnia. Headquartered in
Note Regarding Forward-Looking Statements
Certain statements set forth in this press release constitute "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, but not limited to, statements concerning: the potential therapeutic and commercial value of alixorexton (formerly referred to as ALKS 2680) and the company's expectations regarding the alixorexton development program. The company cautions that forward-looking statements are inherently uncertain. Although the company believes that such statements are based on reasonable assumptions within the bounds of its knowledge of its business and operations, the forward-looking statements are neither promises nor guarantees and they are necessarily subject to a high degree of uncertainty and risk. Actual performance and results may differ materially from those expressed or implied in the forward-looking statements due to various risks and uncertainties. These risks and uncertainties include, among others: whether initial clinical results for alixorexton will be predictive of results of future stages of ongoing clinical studies, future clinical studies or real-world results; whether ongoing or future clinical studies for alixorexton will be initiated or completed on expected timelines or at all; whether alixorexton could be shown to be ineffective or unsafe; potential changes in the cost, scope and duration of the alixorexton development program; and those risks and uncertainties described under the heading "Risk Factors" in the company's Annual Report on Form 10-K for the year ended Dec. 31, 2024 and in subsequent filings made by the company with the U.S. Securities and Exchange Commission (SEC), which are available on the SEC's website at www.sec.gov. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. Except as required by law, the company disclaims any intention or responsibility for updating or revising any forward-looking statements contained in this press release.
1 All p-values presented are unadjusted for multiplicity.
2 Epworth Sleepiness Scale: 8-item self-administered questionnaire that measures severity of excessive daytime sleepiness across multiple conditions over the past 7 days (≤10 = normative).
3 Narcolepsy Severity Scale: 15-item self-administered questionnaire (score: 0-57) that assesses the severity and consequences of the five major narcolepsy symptoms such as daytime sleepiness, cataplexy, hallucinations, sleep paralysis, and disturbed nighttime sleep over the past 7 days.
4 British Columbia Cognitive Complaints Inventory: 6-item self-administered questionnaire (score: 0-18) assessing perceived problems with concentration, memory, expressing thoughts, word finding, slow thinking, and difficulty solving problems over the past 7 days.
5 PROMIS Fatigue: 6-item self-administered questionnaire designed to assess a patients' fatigue over the past 7 days.
6 Buysse, D. Diagnosis and assessment of sleep and circadian rhythm disorders. Journal of Psychiatric Practice. 2005; 11(2):102-115
7 Ten-Blanco M, Flores A, Cristino L, Pereda-Perez I. Targeting the orexin/hypocretin system for the treatment of neuropsychiatric and neurodegenerative diseases: From animal to clinical studies. Frontiers in Neuroendocrinology. 2023;69(101066). https://www.sciencedirect.com/science/article/pii/S0091302223000146
Alkermes Contacts:
For Investors: Sandy Coombs, +1 781 609 6377
For Media: Gretchen Murphy, +1 781 609 6419
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