A Placebo-Controlled, Double-Blind, Parallel-Group, 24-Month Study with an Open Label Extension Phase to Evaluate the Efficacy and Safety of Elenbecestat (E2609) in Subjects with Early Alzheimer's Disease

开始日期2018-01-26

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Eisai Ltd.

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项与 Eisai Ltd. 相关的文献（医药）

2024-08-01·Alzheimer's & Dementia

Plasma pTau217 predicts continuous brain amyloid levels in preclinical and early Alzheimer's disease

Article

作者: Doherty, Thomas ; Murali, Leema Krishna ; Reyderman, Larisa ; Kramer, Lynn D. ; Devanarayan, Viswanath ; Zhou, Jin ; Llano, Daniel A. ; Dhadda, Shobha ; Sachdev, Pallavi ; Hampel, Harald ; Charil, Arnaud ; Irizarry, Michael C. ; Ye, Yuanqing

AbstractBACKGROUNDThis study investigated the potential of phosphorylated plasma Tau217 ratio (pTau217R) and plasma amyloid beta (Aβ) 42/Aβ40 in predicting brain amyloid levels measured by positron emission tomography (PET) Centiloid (CL) for Alzheimer's disease (AD) staging and screening.METHODSQuantification of plasma pTau217R and Aβ42/Aβ40 employed immunoprecipitation‐mass spectrometry. CL prediction models were developed on a cohort of 904 cognitively unimpaired, preclinical and early AD subjects and validated on two independent cohorts.RESULTSModels integrating pTau217R outperformed Aβ42/Aβ40 alone, predicting amyloid levels up to 89.1 CL. High area under the receiver operating characteristic curve (AUROC) values (89.3% to 94.7%) were observed across a broad CL range (15 to 90). Utilizing pTau217R‐based models for low amyloid levels reduced PET scans by 70.5% to 78.6%.DISCUSSIONpTau217R effectively predicts brain amyloid levels, surpassing cerebrospinal fluid Aβ42/Aβ40's range. Combining it with plasma Aβ42/Aβ40 enhances sensitivity for low amyloid detection, reducing unnecessary PET scans and expanding clinical utility.CLINICALTRIALS.GOV IDENTIFIERSNCT02956486 (MissionAD1), NCT03036280 (MissionAD2), NCT04468659 (AHEAD3‐45), NCT03887455 (ClarityAD)Highlights

Phosphorylated plasma Tau217 ratio (pTau217R) effectively predicts amyloid‐PET Centiloid (CL) across a broad spectrum.

Integrating pTau217R with Aβ42/Aβ40 extends the CL prediction upper limit to 89.1 CL.

Combined model predicts amyloid status with high accuracy, especially in cognitively unimpaired individuals.

This model identifies subjects above or below various CL thresholds with high accuracy.

pTau217R‐based models significantly reduce PET scans by up to 78.6% for screening out individuals with no/low amyloid.

2024-08-01·Neurology and Therapy

Efficacy of Lemborexant in Adults ≥ 65 Years of Age with Insomnia Disorder

Article

作者: Moline, Margaret ; Arnold, Valerie ; Ancoli-Israel, Sonia ; Mishima, Kazuo ; Dang-Vu, Thien Thanh ; Malhotra, Manoj ; Pinner, Kate

BACKGROUNDPharmacologic treatments are available to treat insomnia, a common and burdensome sleep disorder, but may be contraindicated in older adults who are prone to side effects from sleep-promoting drugs. These analyses of sleep diary data from Study E2006-G000-303 (Study 303) investigated the benefits of lemborexant 5 mg (LEM5) and 10 mg (LEM10) in the subgroup age ≥ 65 years with insomnia.METHODStudy 303, a 12-month, double-blind study of LEM5 and LEM10 in adults (age ≥ 18 years) with insomnia disorder (sleep onset and/or maintenance difficulties) assessed subject-reported (subjective) sleep-onset latency (sSOL), sleep efficiency (sSE), wake after sleep onset (sWASO), and total sleep time (sTST). Morning sleepiness/alertness, insomnia severity (Insomnia Severity Index [ISI]), fatigue (Fatigue Severity Scale [FSS]), perceptions of sleep-related medication effects (Patient Global Impression-Insomnia [PGI-I] questionnaire), and safety were also evaluated.RESULTSIn this subgroup of older adults (≥ 65 years; n = 262), there were significantly larger changes from baseline for sSOL, sSE, sTST, and sWASO with LEM5 and LEM10 versus placebo through month 6 (except sWASO month 1), indicating improvement; these improvements were sustained through month 12. Subject-reported increases in morning alertness were significantly greater with one or both LEM doses versus placebo through month 6 and sustained through month 12. There were significantly larger ISI total and daytime functioning score decreases (improvement) from baseline with LEM versus placebo at months 1, 3, and 6 (total score: both doses; daytime functioning: LEM5 month 1 and both doses months 3 and 6) and decreases from baseline FSS at months 1 and 3 (LEM5) and month 6 (both doses), sustained to month 12. Compared with placebo, more subjects reported that LEM (both doses) positively impacted ability to sleep, time to fall asleep, and TST through month 6, sustained to month 12, with no rebound after drug withdrawal. LEM was well tolerated to month 12; mild somnolence was the most common treatment-emergent adverse event.CONCLUSIONSImprovements in subject-reported efficacy in LEM-treated adults age ≥ 65 years with insomnia were observed as early as the first week of treatment and sustained through end of month 12. LEM was well tolerated.CLINICAL TRIALS REGISTRATIONClinicalTrials.gov identifier NCT02952820: E2006-G000-303; Study 303; SUNRISE-2 (First posted: October 2016); EudraCT 2015-001463-39 (First posted: November 2016).

2024-07-01·Gynecologic Oncology

Lenvatinib plus pembrolizumab for patients with previously treated advanced ovarian cancer: Results from the phase 2 multicohort LEAP-005 study

Article

作者: Ghori, Razi ; Lwin, Zarnie ; Saada-Bouzid, Esma ; Yanez, Eduardo ; Cassier, Philippe A ; Girda, Eugenia ; Dutcus, Corina ; Chung, Hyun Cheol ; Senellart, Helene ; Jin, Fan ; Groisberg, Roman ; Okpara, Chinyere E ; González-Martín, Antonio ; Corr, Bradley R ; Basu, Bristi

OBJECTIVESThe phase 2, multicohort, open-label LEAP-005 study evaluated lenvatinib plus pembrolizumab in patients with previously treated advanced solid tumors. We report outcomes from the ovarian cancer cohort.METHODSEligible patients had metastatic/unresectable ovarian cancer and had received 3 previous lines of therapy. Patients received lenvatinib 20 mg/day plus pembrolizumab 200 mg every 3 weeks. Treatment continued until progression, unacceptable toxicity, or (for pembrolizumab) completion of 35 cycles. Primary endpoints were objective response rate (ORR) per RECIST version 1.1 and safety. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), and overall survival (OS).RESULTSThirty-one patients were enrolled. 39% had high grade serous ovarian cancer, 23% were platinum-sensitive, 55% were platinum-resistant, 23% were platinum-refractory, and 84% had tumors that had a PD-L1 combined positive (CPS) score ≥1. ORR (95% CI) was 26% (12%-45%) by investigator assessment and 35% (19%-55%) by blinded independent central review (BICR). Per BICR, median DOR was 9.2 (1.5+ to 37.8+) months. ORRs (95% CI) by BICR were 35% (9/26 patients; 17%-56%) for PD-L1 CPS ≥ 1 disease and 50% (2/4 patients; 7%-93%) for PD-L1 CPS < 1 disease. Median (95% CI) PFS by BICR and OS were 6.2 (4.0-8.5) months and 21.3 (11.7-32.3) months, respectively. Treatment-related AEs occurred in 94% of patients (grade 3-4, 77%). One patient died from treatment-related hypovolemic shock.CONCLUSIONSLenvatinib plus pembrolizumab demonstrated antitumor activity as fourth line therapy in patients with advanced ovarian cancer, and no unanticipated safety signals were identified. Responses were observed regardless of PD-L1 status.

项与 Eisai Ltd. 相关的新闻（医药）

2024-09-12

·GlobeNewswire-Health Care

SEED Therapeutics Appoints Eisai Co., Ltd.’s Dr. Yoshiharu Mizui to Board of Directors

Dr. Mizui is Founder and President of Eisai Innovations, Inc. and Former Global Business Development and Strategy Head in Eisai’s Oncology Business Group Brings Nearly 30 Years of Experience in Drug Discovery and Strategic Business Development KING OF PRUSSIA, Pa., Sept. 12, 2024 (GLOBE NEWSWIRE) -- SEED Therapeutics Inc. (“SEED”), a biotechnology company focused on harnessing and engineering Molecular Glues for targeted protein degradation (TPD) of disease-causing proteins, has appointed Dr. Yoshiharu Mizui from Eisai Co., Ltd. (“Eisai”) to its Board of Directors. Dr. Mizui is Founder and President of Eisai Innovation, Inc., the corporate venture capital arm of Eisai, specializing in investing in biotech startup companies. He also holds leadership roles in Eisai Research and Development as Head of Academic & Industry Alliance, and Head of Collaboration & Incubation. With nearly 30 years of experience in drug discovery, strategy, and business development across multiple therapeutic areas, Dr. Mizui brings a wealth of knowledge to SEED’s Board. Before founding Eisai Innovation, Inc. in 2019, Dr. Mizui was Global Head of Strategy and Business Development in Eisai’s Oncology Business Group and was previously Director of H3 Biomedicine, Inc., and Head of Lead Discovery Biology. He received his BS and PhD in Agricultural Chemistry from Kyushu University. Dr. Mizui’s appointment follows Eisai’s entering into a Strategic Research Collaboration with SEED (with potential value of $1.5 billion) and leading the first $24 million close of SEED’s Series A Financing announced last month. (Click here for related press release.) “Dr. Mizui brings invaluable drug discovery and development insights to the SEED Board and Management as we drive forward on our mission of leveraging SEED’s TPD technology and platform to enhance the quality of life for patients worldwide,” said Dr. Lan Huang, SEED’s Co-Founder, Chairman, and CEO. “His joining at SEED comes at a pivotal time as we advance our high-profile programs into the clinic. Dr. Mizui’s research leadership in the oncology field, including with RBM39 degraders, will be instrumental as SEED advances its priority clinical programs in oncology, as well as in neurodegeneration.” “SEED Therapeutics team has deep knowledge of ubiquitin proteasome system and molecular glue discovery technologies to discover and develop TPD drug candidates. I am pleased and honored to serve on the SEED Board of Directors and support them in their amazing journey to deliver impactful medicines to patients and their families,” said Dr. Mizui. About SEED TherapeuticsSEED Therapeutics is an innovative biotech company focused on harnessing and engineering “Molecular Glues” and TPD to attack previously undruggable targets. Backed by a comprehensive intellectual property portfolio, SEED’s mission is to improve human health by developing novel protein degradation therapeutics to treat diseases that currently have limited treatment options. Through active collaborations with SEED Co-Founders, who are pioneers and thought leaders in the TPD field, SEED has developed a growing pipeline of novel drug candidates in neurodegeneration and oncology now approaching clinical development. SEED has both a research collaboration and investment from Eli Lilly and Company, and Eisai. Learn more by visiting https://seedtherapeutics.com/. Investor Contact:IR@seedtherapeutics.com Media Contact:PR@seedtherapeutics.com

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