Alkermes Presents Data From Phase 1b Study of ALKS 2680 Demonstrating Improved Wakefulness in Patients With Narcolepsy Type 1 at SLEEP 2024
Alkermes Presents Data From Phase 1b Study of ALKS 2680 Demonstrating Improved Wakefulness in Patients With Narcolepsy Type 1 at SLEEP 2024
— Orexin 2 Receptor Agonist ALKS 2680 Demonstrated Clinically Meaningful and Statistically Significant Improvements from Baseline in Mean Sleep Latency Compared to Placebo at All Doses Tested —
所有劑量測試中，促進Orexin2受體的ALKS 2680治療組相對於用藥安慰劑組在平均睡眠潛伏時間上有臨床意義和統計學意義的改善。
— ALKS 2680 Was Generally Well Tolerated at All Doses Tested —
在所有劑量測試中，ALKS 2680都被良好地耐受。
— Vibrance-1 Phase 2 Study of ALKS 2680 in Patients With Narcolepsy Type 1 Is Ongoing —
患有一型嗜睡症（Narcolepsy Type 1）的ALKS 2680的二期臨床試驗（Vibrance-1）正在進行。
DUBLIN, June 3, 2024 /PRNewswire/ -- Alkermes plc (Nasdaq: ALKS) today announced new data from the full narcolepsy type 1 (NT1) cohort of a phase 1b, proof-of-concept study evaluating ALKS 2680, the company's novel, investigational, oral orexin 2 receptor (OX2R) agonist in development as a once-daily treatment for narcolepsy. The data are being presented at SLEEP 2024, the 38th annual meeting of the Associated Professional Sleep Societies (APSS), taking place June 1-5, 2024 in Houston.
都柏林，2024年6月3日 / PRNewswire / - Alkermes plc（納斯達克：ALKS）今天宣佈了一份來自第一B期概念驗證研究的完整一型嗜睡症（NT1）隊列的新數據，該研究評估公司正在開發的一種新型口服Orexin 2受體（OX2R）興奮劑ALKS 2680作爲一種每日一次的嗜睡症治療。此次數據的報告在2024年6月1日至5日的第38屆相關專業睡眠學會（APSS）年會SLEEP 2024中進行。th此次一型嗜睡症患者隊列的測試是第一B期研究，受試者通過每日一次的單一口服運用四個截犯序列隨機使用1mg、3mg、8mg的ALKS 2680和安慰劑在每種治療之間有適當的休息期。此次研究的最初結果在2023年世界睡眠大會上已公開報告四名患者的測試詳情。
The phase 1b study evaluated the safety, tolerability, pharmacokinetics and pharmacodynamics of ALKS 2680 via once-daily, single, oral administration. Ten patients with NT1 were randomized1 to one of four crossover sequences in which each participant received 1 mg, 3 mg and 8 mg of ALKS 2680, and placebo, with washout periods between each treatment. Initial results from the first four patients in this NT1 cohort were previously presented at the 2023 World Sleep Congress.
此次從第一B期試驗中得出的數據顯示，在一型嗜睡症患者中，單一ALKS 2680劑量的治療效果顯著。除此之外，患者簡報的警惕度進一步支持了這種可能幫助減輕一型嗜睡症患者日間嗜睡症狀顯著未被滿足的需求的測試。醫學研究負責人Ron Grunstein博士，醫學博士，Woolcock醫學研究協會的睡眠和晝夜節律方向的負責人指出：1此次SLEEP會議上海報（摘要編號1323；海報板423）的主要內容包括：
"Data from this phase 1b study provide evidence of a significant treatment effect of single doses of ALKS 2680 in patients with narcolepsy type 1. In addition, patients' self-reported measures of alertness further support continued clinical development of this investigational treatment, which has the potential to help address significant unmet needs for people living with excessive daytime sleepiness associated with narcolepsy," said Ron Grunstein, M.D., Ph.D., Head of Sleep and Circadian Research at the Woolcock Institute of Medical Research.
"第一B期的研究數據表明單一劑量ALKS 2680對一型嗜睡症的患者有顯著的治療效果。此外，患者自我報告衡量警覺度的結果充分支持這種試驗的持續發展，該試驗有可能幫助緩解一型嗜睡症患者日間嗜睡症狀明顯未被滿足的需求。" Ron Grunstein醫學博士、醫學博士、Woolcock醫學研究所的睡眠和生物鐘研究負責人如此評價試驗結果。
Data highlights from the SLEEP poster presentation (Abstract ID 1323; Poster board 423) include:
SLEEP海報報告主題包括：
Mean Sleep Latency Over 8 Hours:
8個小時內的平均睡眠潛伏期：
- In patients with NT1, treatment with ALKS 2680 demonstrated improved wakefulness compared to placebo at all doses tested, with a clear dose response.
- Treatment with ALKS 2680 resulted in statistically significant and clinically meaningful improvements in mean sleep latency on the Maintenance of Wakefulness Test (MWT), with a mean change from baseline versus placebo of 18.4 minutes at the 1 mg dose (p=0.0002), 22.6 minutes at the 3 mg dose (p=0.0001), and 34.0 minutes at the 8 mg dose (p≤0.0001) (least squares mean difference). Placebo treatment resulted in an approximately 1.4 minute reduction in mean sleep latency from baseline. Prior to treatment with ALKS 2680, these patients had a mean sleep latency on the MWT of approximately six minutes at baseline.2
- At the 3 mg and 8 mg doses, the observed mean MWT scores over an eight-hour period post-dose were within the reported normal range for healthy individuals.3
- 在一型嗜睡症患者中，使用ALKS 2680的治療使人明顯清醒，體現明顯的劑量反應，在治療過程中相對於安慰劑有更好的表現。
- 使用ALKS 2680治療導致在清醒保持測試（MWT）中平均睡眠潛伏期有統計學意義和臨床意義上的改善，該治療相對於安慰劑，在1mg劑量下平均睡眠潛伏期改善18.4分鐘（p = 0.0002），在3mg劑量下改善22.6分鐘(p=0.0001)，在8mg劑量下改善34.0分鐘(p≤0.0001)（最小平方均數差）。與治療前相比，安慰劑治療導致平均睡眠潛伏期減少了1.4分鐘。在進行ALKS 2680治療前，患者基線中的平均睡眠潛伏期約爲6分鐘。2
- 在3mg和8mg的劑量下8小時後觀察到的睡眠潛伏時間（MWT score）在正常健康人群中。3
Patient-Reported Alertness on the Karolinska Sleepiness Scale (KSS):
Karolinska嗜睡量表（KSS）患者報告狀態：
- The KSS is a subjective measure of self-reported alertness over the past five minutes, using a nine-point scale (with 1 being "extremely alert"; 9 being "extremely sleepy"; and 5 being "neither alert nor sleepy"). Change from baseline on KSS was an exploratory endpoint.
- ALKS 2680 demonstrated clinically meaningful, dose-dependent improvements in self-reported alertness in patients with NT1. The average self-reported score at baseline was approximately 7. ALKS 2680 showed improvements of 2 to 3 points in self-reported alertness between 1 and 8 hours, indicating clinically meaningful improvements (p<0.001 at all dose levels vs. placebo).
- KSS是過去五分鐘內自我報告警覺程度的一個主觀評估指標，使用新的量表（1代表“極爲警覺”，9代表“極度疲憊”，5代表“既不警覺也不疲憊”）。KSS的變化是一個探索性的結局指標。
- ALKS 2680在治療一型嗜睡症患者中表現出了劑量相關的臨床意義改善的自我報告警覺量表。基線的平均自我報告得分約爲7，ALKS 2680在1至8小時之間在自我報告的警覺度上有了2到3分的改善，表示明顯的改善(p
Safety:
安全：
- ALKS 2680 was generally well tolerated across all doses tested in patients with NT1. Most treatment-emergent adverse events (TEAEs) were mild in severity, transient and self-resolving (with one moderate case of nausea that resolved with food intake). There were no severe adverse events (AEs). AEs observed in >1 patient and deemed to be related to study drug were insomnia,4 pollakiuria, salivary hypersecretion, decreased appetite, dizziness and nausea.
- There were no serious AEs (SAEs) reported or TEAEs leading to study drug discontinuation in patients with NT1. There were no drug-related, treatment-emergent, clinically meaningful changes from baseline in laboratory values at any dose. Additionally, no cardiovascular safety signals were identified in vital signs or electrocardiogram (ECG) parameters.
- 在一型嗜睡症患者中，使用ALKS 2680的所有劑量治療表現出了很好的耐受性。大多數治療性不良事件（TEAEs）都是輕度的、短暫的且能自我解決（其中一例輕度的噁心在進食後解決）。沒有嚴重不良事件(AEs)發生，發生的與研究藥物相關的AEs有失眠、頻尿、唾液分泌增多、食慾下降、頭暈和噁心。4多尿、口腔分泌物增多、食慾減退、頭暈和噁心。
- NT1患者未報告嚴重的AE（SAE）或TEAEs導致研究藥物停用。任何劑量下的實驗室值從基線開始無藥物相關的治療性新出現的臨床意義上的變化。此外，生命體徵或心電圖（ECG）參數中未發現任何心血管安全信號。
"We're encouraged by the results of this proof-of-concept study of ALKS 2680 in patients with narcolepsy type 1. The clear dose response reinforced our design principles for this program, and we are looking forward to further characterizing the efficacy and safety of ALKS 2680 in patients with narcolepsy type 1 in the ongoing Vibrance-1 phase 2 study," said Craig Hopkinson, M.D., Chief Medical Officer and Executive Vice President, Research & Development at Alkermes.
"我們對ALKS 2680用於NT1患者的概念證明研究的結果感到鼓舞。明顯的劑量反應加強了我們這個項目的設計原則，我們期待在進行中的Vibrance-1第二期研究中進一步評估ALKS 2680的療效和安全性，" 阿爾凱默斯公司首席醫療官兼執行副總裁Craig Hopkinson醫生說。
About the ALKS 2680 Phase 1 Study
The phase 1 study for ALKS 2680 included single-ascending dose and multiple-ascending dose evaluations in healthy volunteers, and double-blind, crossover treatment in patients with narcolepsy type 1 (NT1), narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH).
關於ALKS 2680第一階段研究
ALKS 2680的第一期研究包括健康志願者的單升劑量和多升劑量評估，以及患有納休症1型（NT1）、納休症2型（NT2）和特發性嗜睡症（IH）的患者的雙盲、交叉治療。
In the healthy volunteer phase of the study, each cohort included eight participants, six of whom were randomized to receive ALKS 2680 and two of whom received placebo. In the single-dose portion, ALKS 2680 was dosed from 1 mg to 50 mg. In the multiple-dose portion, participants received single daily doses of ALKS 2680 ranging from 3 mg to 25 mg strengths for up to 10 days. The objectives of this part of the study were to assess ALKS 2680's safety, tolerability, pharmacokinetics (PK) and pharmacodynamics.
在健康志願者階段，每個隊列包括八名參與者，其中六名被隨機分配接受ALKS 2680，兩名接受安慰劑。在單劑量部分，ALKS 2680的劑量從1毫克到50毫克。在多劑量部分，參與者每天接受單次劑量的ALKS 2680，劑量範圍爲3毫克至25毫克的強度，持續10天。這部分研究的目標是評估ALKS 2680的安全性，耐受性，藥代動力學（PK）和藥效動力學。
The phase 1b proof-of-concept part of the study enrolled patients with NT1 (n=10), NT2 (n=9) or IH (n=8). Following an initial two-week washout period of existing medications, patients received single doses of three active dose levels of ALKS 2680 (1 mg, 3 mg and 8 mg for NT1; 5 mg, 12 mg and 25 mg for NT2 and IH) and placebo in a randomized sequence in a four-way crossover design, with washout periods between each treatment in the sequence. The objectives were to assess safety and tolerability, and changes from baseline in average sleep latency, as measured through the Maintenance of Wakefulness Test (MWT) at each crossover period, along with plasma PK, and patient-reported measures of alertness on the Karolinska Sleepiness Scale (KSS).
該階段的概念證明研究分別招募了NT1（n=10），NT2（n=9）或IH（n=8）病人。在現有藥物的初始兩週戒斷期後，病人以隨機順序接受ALKS 2680的三個活動劑量水平（納休症1型的1毫克、3毫克和8毫克；納休症2型和IH的5毫克、12毫克和25毫克）和安慰劑在四向交叉設計中，每個治療中間有間歇期。目標是評估安全性和耐受性，以及每個交叉期通過清醒維持測試（MWT）測量的平均睡眠潛伏期的基線變化，以及血漿PK和基於Karolinska嗜睡量表（KSS）的病人報告的警覺度的測量。
About ALKS 2680
ALKS 2680 is a novel, investigational, oral, selective orexin 2 receptor (OX2R) agonist in development as a once-daily treatment for narcolepsy. Orexin neuropeptides are important regulators of the sleep/wake cycle through OX2R activation, and loss of orexinergic neurons in the brain is associated with excessive daytime sleepiness and cataplexy in narcolepsy.5 ALKS 2680 was designed to address the underlying pathology of narcolepsy with the goal of improving duration of wakefulness and providing cataplexy control. Once-daily oral administration of ALKS 2680 was previously evaluated in a phase 1 study in healthy volunteers and people living with narcolepsy type 1, narcolepsy type 2 and idiopathic hypersomnia and is currently being evaluated in the Vibrance-1 phase 2 study in patients with narcolepsy type 1.
關於ALKS 2680
ALKS 2680是一種新型調查用口服、選擇性的二肽類2型受體（OX2R）激動劑，用於治療納休症。二肽類神經肽通過OX2R激活是睡眠/清醒循環的重要調節劑，腦內二肽類能神經元的喪失與納休症中的異常白天嗜睡和強直症有關。5ALKS 2680的設計旨在改善清醒持續時間和提供強直症控制，並解決納休症的基本病理學。ALKS 2680的每日一次口服給藥曾在健康志願者和患有納休症1型、納休症2型和特發性嗜睡症的人中進行了第一階段的評估，並當前正在進行Vibrance-1第二期研究，以評估納休症1型患者的療效和安全性。
About the Vibrance-1 Study
Vibrance-1 is a phase 2, randomized, double-blind, dose-range-finding study evaluating the safety and efficacy of ALKS 2680 compared to placebo in patients with narcolepsy type 1. More information can be found at www.clinicaltrials.gov (identifier: NCT06358950) and www.vibrancestudies.com (for U.S. audiences only).
關於Vibrance-1研究
Vibrance-1是一項第二期、隨機、雙盲、劑量範圍確定性研究，評估ALKS 2680與安慰劑在納休症1型患者中的安全性和療效。更多信息可在www.clinicaltrials.gov（識別號：NCT06358950）和www.vibrancestudies.com（僅適用於美國受衆）網站上找到。www.clinicaltrials.gov 和 www.vibrancestudies.com（僅適用於美國受衆）。
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. Headquartered in Ireland, Alkermes also has a corporate office and research and development center in Massachusetts and a manufacturing facility in Ohio. For more information, please visit Alkermes' website at www.alkermes.com.
關於阿爾凱默斯公
阿爾凱默斯公是一家全球神經科學生物製藥公司，致力於開發創新型藥物。該公司擁有一系列專有的商業產品，用於治療酒精依賴、阿片類依賴、精神分裂症和I型躁狂症，以及發展中的臨床前和臨床階段的候選藥物，用於治療神經系統疾病，包括納休症。阿爾凱默斯公總部位於愛爾蘭，在馬薩諸塞州擁有一家企業辦事處和研發中心，在俄亥俄州擁有一家制造工廠。有關更多信息，請訪問阿爾凱默斯公司的網站 www.alkermes.com .
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 clinical development activities for, and the potential therapeutic and commercial value of, ALKS 2680 for the treatment of narcolepsy. 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 ALKS 2680 could be shown to be ineffective or unsafe; whether preclinical and initial clinical results for ALKS 2680 will be predictive of results of future clinical studies or real-world results; whether future clinical trials or future stages of ongoing clinical trials for ALKS 2680 will be initiated or completed on time or at all; 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, 2023 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.
關於前瞻性聲明的說明
本新聞稿中所述的某些陳述構成《1995年修正版私人證券訴訟改革法》內含的“前瞻性陳述”，包括但不限於，有關ALKS 2680治療納休症的臨床開發活動和潛在治療和商業價值的聲明。公司警告說，前瞻性陳述本質上是不確定的。儘管公司認爲這些陳述基於其對業務和運營範圍內合理假設的知識，但前瞻性陳述既不代表承諾也不保證，它們必然面臨高度的不確定性和風險。由於各種風險和不確定性，實際業績和結果可能與前瞻性陳述中所表達或暗示的表現和結果存在實質性差別。這些風險和不確定性包括但不限於：ALKS 2680是否無效或不安全；ALKS 2680的臨床前和初始臨床結果是否能夠預測未來的臨床研究結果或真實世界的效果；AL最終是否將開始或完成ALKS 2680的未來臨床試驗或正在進行的臨床試驗的未來階段；以及公司在年終結束於2023年的《表格10-K》中和其後向U.S.證券交易委員會（SEC）提交的文件中所描述的“風險因素”下所描述的那些風險和不確定性，在SEC的網站上可以查詢。www.sec.gov現有和潛在的投資者應謹慎，不應過分依賴這些前瞻性聲明，這些只在此日期有效。除非法律要求，公司否認更新或修訂本新聞稿中包含的任何前瞻性聲明的任何意圖或責任。
1 Nine of 10 participants completed all 4-way randomized crossover periods. One participant withdrew from the study after receiving the initial ALKS 2680 dose due to poor venous access and inability to undergo further blood draws.
110名參與者中有9名完成了所有4種隨機交叉期。一名參與者在接受初步的ALKS 2680劑量後退出了研究，由於靜脈通路不暢和不能進行進一步的採血。
2 Patients with NT1 in the phase 1b study had baseline sleep latencies ranging from one to 15 minutes.
2 1b期研究中的NT1患者基線睡眠潛伏期範圍爲1到15分鐘。
3 Krahn LE, Arand DL, Avidan AY, et al. Recommended protocols for the Multiple Sleep Latency Test and the Maintenance of Wakefulness Test in adults: guidance from the American Academy of Sleep Medicine. J Clin Sleep Med. 2021;17(12):2489–2498.
3Krahn LE，Arand DL，Avidan AY等。美國睡眠醫學學會提供的適用於成人的多重睡眠潛伏期測試和維清醒測試的推薦方案：指南。J Clin Sleep Med。2021年；17（12）：2489-2498。
4 Insomnia includes TEAE terms of insomnia and middle insomnia (i.e., difficulty maintaining sleep).
4失眠包括失眠和中等失眠（即，難以維持睡眠）的TEAE術語。
5 Nagahara T, Saitoh T, Kutsumura N, Irukayama-Tomobe Y, Ogawa Y, Kuroda D, Gouda H, Kumagai H, Fujii H, Yanagisawa M, Nagase H. Design and Synthesis of Non-Peptide, Selective Orexin Receptor 2 Agonists. J Med Chem. 2015 Oct 22;58(20):7931-7. doi: 10.1021/acs.jmedchem.5b00988. Epub 2015 Aug 26. PMID: 26267383.
5Nagahara T，Saitoh T，Kutsumura N，Irukayama-Tomobe Y，Ogawa Y，Kuroda D，Gouda H，Kumagai H，Fujii H，Yanagisawa M，Nagase H。非肽，選擇性的皮下睡眠激素受體2激動劑的設計和合成。J Med Chem。2015年10月22日;58（20）：7931-7。doi：10.1021/acs.jmedchem.5b00988。在線發表於2015年8月26日.PMID：26267383。
Alkermes Contacts:
For Investors: Sandy Coombs, +1 781 609 6377
For Media: Gretchen Murphy, +1 781 609 6419
阿爾凱默斯聯繫人：
投資者聯繫人：Sandy Coombs，+1 781 609 6377
媒體聯繫人：Gretchen Murphy，+1 781 609 6419
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SOURCE Alkermes plc
來源 阿爾凱默斯有限公司
譯文內容由第三人軟體翻譯。