A Parallel Group, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Eptinezumab Administered Intravenously in Subjects Experiencing an Acute Attack of Migraine

The purpose of this study is to evaluate the efficacy and safety of eptinezumab administered intravenously in participants experiencing an acute attack of migraine.

开始日期2019-11-07

申办/合作机构

H. Lundbeck A/S

[+1]

NCT04197349 / Completed临床1期

A Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Phase 1 Study to Determine the Safety, Tolerability, and Pharmacokinetics of ALD1910, a Humanized Anti-Pituitary Adenylate Cyclase Activating Peptide (PACAP) Monoclonal Antibody

The purpose of this study is to determine the safety, tolerability and pharmacokinetics of ALD1910, a monoclonal antibody, administered by intravenous infusion and subcutaneous injection.

开始日期2019-09-24

申办/合作机构

H. Lundbeck A/S

[+1]

NCT02985398 / Completed临床3期

An Open Label Phase 3 Trial to Evaluate the Safety of ALD403 Administered Intravenously in Patients With Chronic Migraines

An evaluation of long term safety of repeat ALD403 doses in Chronic Migraine

开始日期2016-12-01

申办/合作机构

Lundbeck Seattle BioPharmaceuticals, Inc.

100 项与 Lundbeck Seattle BioPharmaceuticals, Inc. 相关的临床结果

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2022-12-01·The journal of headache and pain1区 · 医学

Eptinezumab treatment initiated during a migraine attack is associated with meaningful improvement in patient-reported outcome measures: secondary results from the randomized controlled RELIEF study

1区 · 医学

ArticleOA

作者: Buse, Dawn C ; Winner, Paul K ; Cady, Roger ; Chakhava, George ; McAllister, Peter ; Mehta, Lahar ; Josiassen, Mette Krog ; Lindsten, Annika ; Lipton, Richard B ; Ailani, Jessica ; Ettrup, Anders

Abstract:

Background:

Demonstrating therapeutic value from the patient perspective is important in patient-centered migraine management. The objective of this study was to investigate the impact of eptinezumab, a preventive migraine treatment, on patient-reported headache impact, acute medication optimization, and perception of disease change when initiated during a migraine attack.

Methods:

RELIEF was a randomized, double-blind, placebo-controlled trial conducted between 2019 and 2020 in adults with ≥1-year history of migraine and 4–15 migraine days per month in the 3 months prior to screening. Patients were randomized (1:1) to a 30-min infusion of eptinezumab 100 mg or placebo within 1–6 h of a qualifying migraine attack onset. The 6-item Headache Impact Test (HIT-6) and 6-item Migraine Treatment Optimization Questionnaire (mTOQ-6) were administered at baseline and week 4, and the Patient Global Impression of Change (PGIC) at week 4. A post hoc analysis of these measures was conducted in patients who reported headache pain freedom at 2 h after infusion start.

Results:

Of 480 patients enrolled and treated, 476 completed the study and are included in this analysis. Mean baseline HIT-6 total scores indicated severe headache impact (eptinezumab, 65.1; placebo, 64.8). At week 4, the eptinezumab-treated group demonstrated clinically meaningful improvement in HIT-6 total score compared with placebo (mean change from baseline: eptinezumab, − 8.7; placebo, − 4.5; mean [95% CI] difference from placebo: − 4.2 [− 5.75, − 2.63], P < .0001), with greater reductions in each item score vs placebo (P < .001 all comparisons). Change in HIT-6 total score in the subgroup with 2-h headache pain freedom was − 13.8 for the eptinezumab group compared with − 4.9 for the placebo group. mTOQ-6 total score mean change from baseline favored eptinezumab (change, 2.1) compared with placebo (1.2; mean [95% CI] difference: 0.9 [0.3, 1.5], P < .01). More eptinezumab-treated patients rated PGIC as much or very much improved than placebo patients (59.3% vs 25.9%).

Conclusions:

When administered during a migraine attack, eptinezumab significantly improved patient-reported outcomes after 4 weeks compared with placebo, with particularly pronounced effects in patients reporting headache pain freedom at 2 h after infusion start.

Trial registration:

ClinicalTrials.gov Identifier: NCT04152083. November 5, 2019.

2022-03-01·Clinical therapeutics4区 · 医学

Impact of Baseline Characteristics on the Efficacy and Safety of Eptinezumab in Patients With Migraine: Subgroup Analyses of PROMISE-1 and PROMISE-2

4区 · 医学

Article

作者: Giorgadze, Gvantsa ; Martin, Vincent ; Hirman, Joe ; Mehta, Lahar ; Nagy, A Jim ; Cady, Roger ; Janelidze, Marina ; Buse, Dawn C

PURPOSE:

In the PROMISE-1 (Prevention of Migraine via Intravenous ALD403 Safety and Efficacy-1) and PROMISE-2 (Prevention of Migraine via Intravenous ALD403 Safety and Efficacy-2) clinical trials, eptinezumab 100 mg and 300 mg met the primary efficacy end point, significantly reducing mean monthly migraine days across weeks 1 to 12. Clinical efficacy was also shown across key secondary end points. However, to determine if clinical efficacy varies across subgroups, it is necessary to determine efficacy in patients with different sociodemographic features and headache characteristics. These post hoc analyses of patients in PROMISE-1 and PROMISE-2 evaluated the impact of intrinsic factors on the efficacy and safety of eptinezumab in subgroups defined according to baseline demographic and migraine disease characteristics.

METHODS:

PROMISE-1 and PROMISE-2 were Phase III, parallel-group, double-blind, randomized, placebo-controlled trials of repeat quarterly intravenous infusions of eptinezumab or placebo in adults with episodic (PROMISE-1) or chronic (PROMISE-2) migraine.

FINDINGS:

Demographic and baseline characteristics were similar across treatment groups in both the PROMISE-1 and the PROMISE-2 studies. Analyses did not show a clear pattern of baseline demographic characteristics driving treatment effects except for the obesity subgroups. For the ≥50% migraine responder rate in the obese class I (body mass index 30.0-35.0 kg/m²) subgroup, although separation from placebo was not as large (<10% separation compared with ≥10% separation across most baseline demographic factors), both doses showed improved ≥50% migraine responder rate compared with placebo, with slightly better results in patients receiving eptinezumab 300 mg.

IMPLICATIONS:

Eptinezumab treatment showed consistent clinically relevant reductions from baseline in mean monthly migraine days compared with placebo based on ≥50% migraine responder rate across clinically important intrinsic subgroups of adults with episodic or chronic migraine.

CLINICALTRIALS:

gov identifiers: NCT02559895 (PROMISE-1) and NCT02974153 (PROMISE-2).

2021-12-20·Bioengineered4区 · 生物学

The eptinezumab:CGRP complex structure – the role of conformational changes in binding stabilization

4区 · 生物学

ArticleOA

作者: Scalley-Kim, Michelle ; David, Laurent ; Misura, Kira ; Olland, Andrea ; White, Andre

To further elucidate the mechanism of action and binding properties of eptinezumab to calcitonin gene-related peptide (CGRP), X-ray crystallography, computational alanine scanning, and molecular dynamics were used. X-ray diffraction data were collected to determine the three-dimensional structures of the unbound eptinezumab antigen-binding fragment (Fab) and the Fab:CGRP complex. Molecular dynamics simulations were performed to analyze the transition between uncomplexed and complex states. The amidated C-terminus of CGRP was shown to bind in a pocket formed by the Fab heavy and light chains. There was extensive contact between all six complementarity-determining regions (CDRs; composed of light-chain [L1, L2, and L3] and heavy-chain [H1, H2, H3]) of eptinezumab and CGRP. The complex demonstrated a high ligand-binding surface area dominated by aromatic residues. CDR L3 contains a disulfide bond that stabilizes the loop, contributes surface area to the binding pocket, and provides van der Waals contacts. Comparison of the uncomplexed and complex structures revealed motion near the binding cleft. The CDR loops H2 and H3 were displaced ~1.4-2.0 Å and residue H-Tyr33 changed conformation, creating a 'latch-and-lock' mechanism for binding CGRP and preventing dissociation. Computational alanine scanning of CGRP identified energetic 'hot spots' that contribute to binding energy; mutating these positions to residues in homologous neuropeptides resulted in unfavorable binding energies. The attributes of the Fab region and the conformational changes that occur in eptinezumab during binding to CGRP contribute to the specificity, durability, and strength of the interaction, and likely underlie the rapid and sustained migraine preventive effect observed in clinical studies.

项与 Lundbeck Seattle BioPharmaceuticals, Inc. 相关的新闻（医药）

2024-10-24

·PRNewswire

Jade Biosciences Appoints Tom Frohlich as Chief Executive Officer and Hetal Kocinsky as Chief Medical Officer; Forms Board of Directors and Expands Financing to $95 Million

Mr. Frohlich, formerly Chief Operating Officer of Chinook Therapeutics, brings 20+ years of leadership experience; Dr. Kocinsky offers deep expertise in developing therapies for autoimmune and kidney diseases Board of Directors, comprised of industry veterans in science, business, and strategy, will support the company's growth Expanded financing to accelerate clinical development of Jade's novel therapies targeting autoimmune diseases with significant unmet need VANCOUVER, BC and SAN FRANCISCO, Oct. 24, 2024 /PRNewswire/ -- Jade Biosciences, Inc. ("Jade"), a biotechnology company dedicated to developing best-in-class therapies for patients living with autoimmune diseases, today announced the appointment of Tom Frohlich as Chief Executive Officer (CEO) and Hetal Kocinsky, M.D., as Chief Medical Officer (CMO). The company also introduced its newly formed Board of Directors, marking a significant step in the company's growth trajectory. Jade has extended its financing, bringing the total raised to $95 million. The financing round adds Frazier Life Sciences and Versant Ventures to an investor syndicate that includes Fairmount, Venrock Healthcare Capital Partners, Deep Track Capital, Driehaus Capital Management, Franklin Templeton, RTW Investments, and Braidwell LP. Strategic Appointments to Lead Jade's Next Growth Phase Tom Frohlich, Chief Executive Officer Mr. Frohlich, a biotech and pharma industry veteran, brings over 20 years of experience in company building, business strategy, and product development. Before joining Jade, he co-founded and served as Chief Operating Officer (COO) of Chinook Therapeutics, where he guided the company's growth through to its $3.2 billion acquisition by Novartis in 2023. He also held leadership roles at Arbutus Biopharma, Johnson & Johnson, and Merck, managing key areas such as commercial strategy and business development. "I am honored to join Jade Biosciences and lead this talented team through such an exciting time," said Frohlich. "With a strong balance sheet, world-class investors, and an experienced leadership team, we are well-positioned to advance therapies that will transform patient care in autoimmune diseases." Hetal Kocinsky, M.D., Chief Medical Officer Dr. Kocinsky brings deep expertise in drug development, having led clinical programs from early-stage research to regulatory approvals across multiple therapeutic areas. Most recently, she served as Vice President of Translational Medicine at Chinook and held leadership roles at Apellis and Achillion Pharmaceuticals. A board-certified pediatric nephrologist, she also spent time as an Assistant Professor at the Yale School of Medicine. "I look forward to working alongside the team at Jade in our quest to deliver breakthrough therapies to patients in need," said Dr. Kocinsky. "With my background in translational medicine and experience navigating complex clinical landscapes, I look forward to accelerating solutions that can redefine care for patients with autoimmune diseases." New Board of Directors Brings Industry Expertise and Strategic Insight Jade's newly formed Board of Directors is led by Board Chairman Eric Dobmeier, former President and CEO of Chinook Therapeutics, and brings together industry leaders with expertise across science, business operations, and corporate strategy. The board includes: Chris Cain, Ph.D. – Director of Research, Fairmount Funds Management LLC Eric Dobmeier – Board Chairman, Venture Partner, Samsara BioCapital Tom Frohlich – CEO, Jade Biosciences Tomas Kiselak – Managing Member, Fairmount Funds Management LLC Lawrence Klein, Ph.D. – CEO of Oruka Therapeutics Erin Lavelle – Former COO and CFO at Profound Bio, Eliem Therapeutics; additional leadership roles at Alder BioPharmaceuticals and Amgen About Jade Biosciences Jade Biosciences is developing transformative therapies with the goal of redefining the standard of care for autoimmune diseases. The company launched in July 2024 and has raised $95 million from a strong slate of investors: Fairmount, Venrock Healthcare Capital Partners, Deep Track Capital, Driehaus Capital Management, Franklin Templeton, RTW Investments, Braidwell LP, Frazier Life Sciences, and Versant Ventures. Jade's portfolio was engineered by Paragon Therapeutics. For more information, visit JadeBiosciences.com and follow us on LinkedIn. Media Contact [email protected] SOURCE Jade Biosciences WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

高管变更并购IPO

2024-10-14

·EndPoints

Lundbeck makes $2.6B cash move for Longboard a month after starting Phase 3 in Dravet syndrome

Danish drugmaker Lundbeck will buy La Jolla, CA-based Longboard Pharmaceuticals for $2.6 billion in cash, the companies said Monday morning, marking the largest biopharma M&A deal since July . Neuroscience-focused Lundbeck will get access to a 5-HT2C superagonist that just entered Phase 3 last month for Dravet syndrome, a severe type of epilepsy found in infancy. The experimental medicine, known as bexicaserin, could also apply to other developmental and epileptic encephalopathies like Lennox-Gastaut syndrome and CDKL5 deficiency disorder, the company has said. Lundbeck projects a launch of bexicaserin in the last quarter of 2028 and global peak sales potential of up to $2 billion. The drugmaker also gets an S1P receptor modulator dubbed LP659 that is in Phase 1 and could be tested in multiple neurological diseases. Lundbeck CEO Charl van Zyl said Longboard will “become a cornerstone in Lundbeck’s neuro-rare franchise.” “Bexicaserin addresses a critical unmet need for patients suffering from rare and severe epilepsies, for which there are very few good treatment options available,” van Zyl said in a statement. Longboard spun out of Arena Pharmaceuticals with $56 million in October 2020. It went public five months later. Pfizer then bought Arena for $6.7 billion in December 2021. The deal comes amid a relatively dull past few months for public biopharma M&A, with many of the recent deals falling below $1.3 billion. There has been no deal of $5 billion or higher yet in 2024. Lundbeck itself has been relatively quiet on the acquisition front since its $1.95 billion Alder BioPharmaceuticals deal in September 2019. That led to a migraine drug approval a few months later for Vyepti . The Longboard deal is slated to close this quarter, and both boards have approved it, the companies said. Longboard will be bought for $60 per share $LBPH . Its share price skyrocketed 50% to $58 in premarket trading.

并购上市批准临床3期临床1期

2024-03-20

·药时代

做了两年多的药企CEO，倦了

2023年2月9日，鲍勃·阿塞尔比（Bob Azelby）黯然离开了工作时长2年半的Eliem Therapeutics。鲍勃作为Eliem的首任CEO，与其同批离开的还有全司55%的员工。Eliem是一家十分年轻的公司，2019年在RA Capital Management、Access Biotechnology 等投资机构的资助下成立并一直处于隐匿模式。直至2023年3月，Eliem凭借一则“我司获得8000万美元融资”的新闻稿，正式对外亮相，那时鲍勃已然是该公司的CEO了。Eliem的定位十分清晰，专注于CNS治疗领域。尽管公司刚刚出道，但旗下已然拥有慢性疼痛治疗药物ETX-810（两项2a期临床进行中）、抗精神类药物ETX-155（即将启动多项2a期临床）两款候选药物。这对刚从Alder BioPharmaceuticals离开的鲍勃而言，可谓是“神仙开局”。不同于众多深耕CNS领域中的学术大佬，鲍勃是商务出生且工作履历颇为曲折。青年时期的鲍勃，先是在安进做了15年商务，后去了Juno Therapeutics做了3年首席商务官，但由于公司被Celgene Corporation收购，再次转战Alder BioPharmaceuticals，而鲍勃也是在这份工作履历中正式涉足CNS治疗领域。鲍勃是2018年加入Alder的，任CEO一职。彼时的Alder作为CNS领域明星企业，被灵北看中后，于2019年以近20亿美元收购，2020年FDA批准首款用于预防成人偏头痛药物eptinezumab（Alder原研）。尽管这段工作经历颇为短暂，但也成就了鲍勃在CNS治疗领域中的管理地位。Eliem的CEO，鲍勃“当仁不让”。时间来到2021年5月，即Eliem“出世”2个月后，公司再获6000万美元B轮融资，同年8月成功IPO，获9200万美元股权融资。鲍勃在2021年半年报中慷慨表示，“对于Eliem，这是激动人心的一年，我们将用这些资金去推动手中这些具有潜力的产品，致力于CNS治疗药物的开发。”然而，就是这般慷慨激昂的言论，2年后的鲍勃怎么也说不出了。在鲍勃任职Eliem CEO的2年时间里，核心管线相继受挫。先是进展最快的ETX-810在用于糖尿病周围神经性疼痛和腰骶神经根疼痛的两项2a试验失败（2022年8月停止开发），后是ETX-155在早期研究中出现CMC问题，多项临床研究被推迟。终于在2023年2月，Eliem宣布暂停ETX-155的开发（已经完成1期临床用于抑郁症研究），为了符合股东最佳利益，反而将研发重心再次转向聚焦临床前产品ETX-123，并裁员55%，这其中也包括鲍勃的离开。所谓“人挪活树挪死”。离开之后的鲍勃，加入了ADC Therapeutics、Cardinal Health等多家药企的董事会，日子要相比在Eliem作全职CEO时，相对安心。而Eliem在2023年7月宣布“计划探索战略代替方案”，并停掉了最后一个项目ETX-123。截止2023年6月30日，该公司拥有未经审计的初步现金、现金等价物及可流通证券投资总额约为 1.026 亿美元。可以说，Eliem正处在破产清算的边缘。直至2024年3月19日，Eliem宣布计划并购一家名为Tango的Biotech，初步估值为2000万美元，交易方式为股价换购。值得一提的是，Tango由RA Capital Management关联基金控制，而RA本身就是Eliem的大股东，此次收购有助于整合内部资源，降低未来发展的风险。当然，这一切，对于鲍勃没有太大关系了。点击这里，观看精彩直播！

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药物(靶点)	适应症	全球最高研发状态

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