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福利 | 连续流系列白皮书领取扫码登记信息并留言“连续流白皮书系列”，即可获取由药石科技提供的下列技术资料（工作人员会通过登记的邮箱发送，请务必填写正确信息）：《Techwhitepaper-flowchemsitry_diazotizationreaction》《连续光催化技术的研究》《连续流技术手册》《药石科技2024年环境、社会及公司治理报告》......API生产被认为是化学行业中能源和材料消耗最大的行业之一，仅在2023年就产生了3.58亿吨温室气体排放，相当于全球二氧化碳排放量的6%，超过了汽车行业。在过去二十年中，连续流动过程已成为API制备中间歇过程的潜在替代方案，许多药物已转向连续流动操作。2025年2月发表于《ACS Sustainable Chemistry & Engineering》的论文《Sustainability and Techno-Economic Assessment of Batch and Flow Chemistry in Seven Industrial Pharmaceutical Processes》，对间歇和流动化学在工业制药过程中的应用进行了全面的可持续性和技术经济评估。文中对比了间歇和流动化学在合成七种工业相关活性药物成分（APIs）时的表现。在技术经济层面，连续流工艺的能源效率比间歇工艺提高一个数量级，能耗平均降低约78%，资本成本可降低50%；从生命周期分析来看，连续流工艺在水消耗、二氧化碳排放和废弃物产生（E因子平均降低87%）等方面表现更优。 总而言之，文献指出连续流技术在制药过程中优势显著，凸显了其在绿色API制造方面的潜力，为实现更可持续的制药生产提供了方向，也为药企研发生产策略的制定提供了依据。论文摘录EXCERPTS FROM THE ARTICLE01引言在过去二十年中，连续流动过程已成为API制备中间歇过程的潜在替代方案，许多药物已转向连续流动操作。与间歇反应器相比，流动技术有望更好地控制操作条件，实现更安全的操作、更均匀的混合、减少废弃物产生、增强传递现象，并降低溶剂和能源的使用。在本研究中，我们首次对七种不同API的制造过程进行了完整的技术经济分析（TEA）和生命周期评估（LCA），填补了文献空白。02结果与讨论本分析聚焦于七种API：盐酸阿米替林、他莫昔芬、唑吡坦、卢非酰胺、青蒿琥酯、布洛芬和苯丁胺。选择这些API是因为它们具有工业相关性和多样的化学性质。这些API涵盖了一系列治疗应用，包括抗抑郁药（阿米替林）、抗癌药（他莫昔芬）、镇静剂（唑吡坦）、抗癫痫药（卢非酰胺）、抗疟药（青蒿琥酯）、非甾体抗炎药（布洛芬）和神经活性化合物（苯丁胺）。通过选择具有不同化学结构和合成途径的API，旨在全面评估经济可行性和环境影响，使研究结果更广泛地适用于制药行业，并更具严谨性。过程模拟和技术经济分析使用Aspen Plus V11进行，而环境评估则使用SimaPro V9.5完成。2.1 七个过程的技术经济分析 我们首先进行技术经济分析，以评估流动技术的可行性和成本效益。我们量化了两种配置下的能源使用情况。一般来说，间歇制造过程的能源消耗范围为1×10-1Wh-1gproduct-1至1×102Wh-1gproduct-1。相比之下，连续流动过程的能源消耗显著更低，范围为10-2Wh-1gproduct-1至101Wh-1gproduct-1。从定量角度来看，连续流动过程的能源效率比间歇过程提高了一个数量级，总体提升始终超过30%，平均提高约78%（图2a）。布洛芬的流动过程能源效率提升最高，达到97%。苯丁胺过程的能源消耗也显著降低了91%，从9.51Wgproduct-1h-1降至0.82Wgproducth-1。这些结果源于连续流动技术提高了生产力，在更短的时间内实现了更高的产率和更多的目标产品。他莫昔芬过程的能源效率提升最小，从1.49Wgproduct-1h-1降至0.99Wgproducth-1。连续流动系统中能源效率的提高归因于连续流动技术的几个固有特性。我们探索了与多个因素（如反应动力学、先进的传质和传热）的相关性，但发现能源效率主要仅与过程持续时间相关。这表明，连续流动系统中较短的反应时间本质上需要较少的电力，从而导致总能源消耗降低。图2b展示了七个过程的这种关系。图2c展示了间歇和流动过程能源消耗的统计分析，证明了两种方法在能源效率上的性能差异。间歇过程的平均能源消耗约为103kWh。相反，流动过程的能源消耗在统计上显著降低，约为101-102kWh。图3a展示了过程的资本成本支出及其降低情况。间歇配置的成本估计在300万美元至700万美元之间，而连续流动技术的成本范围为200万美元至400万美元。从经济角度来看，连续流动方法导致资本成本支出的下降幅度较小。在资本成本降低方面，卢非酰胺过程表现最佳，成本从703万美元降至352万美元，几乎下降了50%。图3b对七种API的间歇和流动过程的资本成本进行了统计研究。间歇过程的平均运营成本略低于流动配置。运营成本的差异主要归因于基础设施和仪器费用的不同，这些费用几乎占总成本的50%。间歇过程较高的平均成本和成本差异表明，该方法需要资源更密集的基础设施。实际上，在连续系统中，反应器以恒定的进料和反应物流量运行，这允许进行紧凑设计，优化传质和传热。反应器体积的减小直接降低了所需的建筑材料数量和相关成本。除了资本成本支出，还评估了年度运营成本，考虑了原材料、公用设施和维护费用（图3c）。间歇制造过程的平均年度运营成本约为364万美元，而流动配置的费用略有降低，平均约为336万美元。然而，对于这七个过程，运营成本的变化在统计上并不显著（图3d）。 此外，我们进行了一项为期15年、贴现率为8%的净现值（NPV）预测研究，以展示在所有七种API的生产中，流动过程相对于间歇过程明显的财务优势。最初，由于需要高额的资本投资，两种方法的NPV值均为负。然而，流动过程始终能更快达到收支平衡点，根据不同的API，收支平衡时间在第7年至第12年之间，而间歇过程的收支平衡点则在第9年至第14年之间。流动过程能够更早实现收支平衡，归因于其较低的运营成本、较少的资源消耗和更精简的操作。此外，流动过程的NPV分析曲线斜率比间歇过程更陡峭，表明随着时间的推移其盈利能力增长更高。到15年期末，流动过程在所有API上的NPV值始终更高，反映出其卓越的长期经济可行性。间歇和流动方法的NPV曲线之间的差距不断扩大，凸显了流动过程在财务上的累积优势，这源于其在能源、溶剂和水使用方面的效率，以及较低的环境影响，正如先前的分析所示。2.2 七个过程的生命周期分析 为了评估制造过程的环境影响和可持续性，我们接着对七个选定的过程进行了全面的LCA，以确定可以改进的关键领域，量化资源消耗，并评估每个过程相关的排放。 在水消耗方面（图4a），间歇制造过程的单位产品用水量在10-2至101m3之间，而连续流动过程的用水量则显著更低，在10-3至10-1m3之间。这表明连续流动过程的用水量比间歇过程少一到两个数量级，用水量减少了50%至90%。连续流动过程中用水量的减少可归因于该技术的几个固有因素。连续流动系统通常在较低的温度和压力下运行，从而更有效地利用试剂和溶剂。这种效率降低了冷却和清洗单元操作所需的用水量。此外，连续流动系统的紧凑设计和对反应参数的更好控制，进一步减少了对溶剂和水的需求，因为反应在更可控的稳态环境中进行，最大限度地减少了处理和加工阶段对过量水的需求。布洛芬生产过程的用水量减少幅度最大，每克目标产品的总溶剂使用量减少了99%，从间歇过程的20.70 m3降至连续流动方法的5.4 m3。相比之下，青蒿琥酯生产过程的总用水量减少幅度最小，仅减少了46%，从0.0072m3降至0.0039m3，远低于七种制药过程中大多数过程81%的平均减少幅度。水消耗和电力使用之间存在相关性（图4b）。具体而言，较低的水使用量与较少的电力消耗相关，因为冷却和加工操作所需的能源较少。实际上，在评估制造过程时，水-能源关系是一个关键考虑因素，因为水消耗和电力使用相互依存。统计分析支持了间歇和流动过程之间水消耗的差异（图4c）。图4d展示了对土地系统变化的影响，这考虑了技术对森林砍伐和自然栖息地破坏的影响。观察发现，间歇过程对土地系统的影响范围为每单位产品10-4至10-2m2，而连续流动方法使这一影响略微降低了一个数量级，范围为每单位产品10-4至10-3m2。以1克产品为例，苯丁胺过程表现最佳，土地系统变化从间歇过程的0.00468m2降至流动过程的0.00015m2，降幅达97%，这是由于甲苯和四氢呋喃的使用量从间歇过程的23.3ggproduct-1和17.1ggproduct-1分别降至流动过程的7.6ggproduct-1和0.1ggproduct-1。此外，布洛芬的土地系统变化减少了超过85%，这是因为甲醇溶剂的使用量减少（从间歇过程的48.2ggproduct-1降至流动过程的3.5ggproduct-1）。然而，卢非酰胺过程的土地系统变化仅减少了30%，这是因为两种配置在制造过程中使用的二甲基亚砜（DMSO）量相似，分别为14.0gDMSOgproduct-1和11.9gDMSOgproduct-1。图4e中土地系统变化与溶剂使用之间的相关性可归因于溶剂生产和处置对环境的影响。溶剂生产所需的原材料提取通常涉及土地用途的改变，包括森林砍伐和栖息地破坏。因此，减少溶剂消耗不仅可以降低制造过程的直接环境影响，还可以减少与溶剂生命周期管理相关的土地用途变化。在苯丁胺和布洛芬的案例中，溶剂使用量的显著减少导致土地系统变化大幅降低，这表明制造业中有效的资源管理有助于最小化生态破坏。相反，在卢非酰胺过程中，溶剂使用量的减少有限，导致土地系统变化的减少幅度也较小，这凸显了优化溶剂利用作为促进制药制造业环境可持续性策略的重要性。图4f中的统计分析支持了这些发现，尽管它也表明土地系统变化的差异在统计上并不显著，这可能意味着间歇和流动配置之间的溶剂消耗并没有显著差异。这可能意味着，虽然连续流动过程通常预期会因连续操作和效率提高而减少溶剂使用，但在实际中，这种减少并不明显。这可能是由于在反应控制、清洗或分离步骤中需要相当数量的溶剂，使得两种过程的总体溶剂消耗相对相似。 我们通过评估绿色度（考虑E因子（每单位产品的废弃物质量）和碳排放（kgCO2当量））来研究七个过程的环境性能。连续流动过程相对于目标产品产生的废弃物更少（图5a）。实际上，间歇过程的E因子范围在10至110之间，而连续流动技术的表现明显优于间歇方法，E因子范围为2至20，平均降低了87%。这种改进可归因于连续流动技术的内在特性，包括总体产率更高、废弃物产生量更低，以及如上文所述的溶剂使用量的减少。值得注意的是，从传统间歇反应器转变为连续流动方法时，青蒿琥酯工艺是绿色生产的一个典范，其E因子下降了97%。此外，苯丁胺和布洛芬工艺也呈现出类似趋势，分别下降了约93%。卢非酰胺工艺的E因子降幅最小，为85%。图5b展示了间歇工艺中较高的E因子，很好地说明了间歇系统中产生废弃物的倾向较高。 然而，需要注意的是，虽然E因子能为废弃物产生情况提供有价值的见解，但它并未考虑生产过程中的碳排放。这一局限性意味着，仅靠E因子可能无法全面反映制造过程对环境的影响，特别是在温室气体排放方面。碳排放可能来自多种来源，包括加热、冷却或相变所需的能源密集型热过程，以及溶剂蒸发、试剂分解和副产物形成。此外，排放还可能源于上游活动，如原材料提取、运输和提纯，以及下游加工步骤，如分离、提纯和废物处理。因此，我们也对间歇和流动方法的碳（CO2）排放进行了评估（图5c、d）。 间歇配置的碳排放（kg的CO2当量）范围在10-1到101数量级，而通过实施连续流动方法，排放范围在10-2到10-1。流动技术使碳排放显著降低了一个数量级，平均降低79%。与E因子的结果类似，布洛芬工艺在碳排放减少方面表现出色，从排放0.41kg的CO2当量降至0.01kg的CO2当量，降幅达97%。这是因为间歇反应器生产相同数量的产品所需时间更长，导致整个制造阶段的电力消耗更高。此外，苯丁胺工艺也遵循这一良好趋势，碳排放从0.43kg的CO2当量降至0.02 kg的CO2当量，下降了95%。最后，盐酸阿米替林工艺采用连续流动方法后，碳排放的最小化程度最低，为45% 。 这些发现突出了CO2排放、水消耗和能源使用之间相互作用的重要见解。最后，在流动化学领域，我们首次针对九大行星边界分析了这七个工艺的环境影响，包括海洋酸化、生物圈完整性（功能和遗传方面）、碳排放、大气气溶胶负荷、土地系统变化、生物地球化学流（磷和氮循环方面）和淡水使用。七个工艺的海洋酸化平均降低了72%。苯丁胺工艺的降幅最大，为95%，这是由于与间歇工艺相比，连续流动方法的电力消耗和操作时间更低，以及苯甲醛原料使用量的减少。布洛芬工艺在海洋酸化方面也有92%的显著降低。相比之下，盐酸阿米替林工艺的降幅最小，为41%，主要是由于四氢呋喃（THF）使用量的减少。大气气溶胶负荷是一个与人类健康相关的关键环境类别，因为细颗粒物会影响空气质量。在苯丁胺和布洛芬工艺中，大气气溶胶负荷显著降低，分别减少了95%和90%。这些减少主要是由于原甲酸三甲酯（TMOF）和THF使用量的减少。此外，连续流动方法使七个工艺中的五个在磷循环影响方面降低了60%以上。在氮循环方面，苯丁胺工艺表现突出，减少了98%，这主要得益于硝基甲烷和甲苯使用量的减少，凸显了连续流动技术的效率及其较低的溶剂需求。还研究了对遗传生物圈完整性的影响，这与化学物质对生态系统的致癌作用有关。布洛芬工艺在这一类别中实现了98%的降低，主要是由于每克产品中异丁基苯的使用量大幅减少（从1.12 g降至0.21 g）。 03结论我们的分析量化了流动化学的影响，表明连续流动方法在经济可行性和环境影响方面明显优于间歇方法。具体如下：连续流动过程的能源效率提高了一个数量级，与间歇过程相比，能源消耗平均降低78%。 间歇过程的资本成本在300万美元到700万美元之间，而连续流动技术的成本在200万美元到400万美元之间，有可能降低50%。与间歇过程相比，连续流动过程的用水量显著减少（减少50-90%），CO2排放也更低（约79%）。连续流动过程的E因子平均降低了87%（间歇过程为10-110，连续流动过程为2-20）。 ABOUT期刊：ACS Sustainable Chemistry & Engineering 第一作者：Mert Can Ince通讯作者：Gianvito Vilé 通讯单位：Politecnico di Milano（米兰理工大学）论文DOI：10.1021/acssuschemeng.4c09289识别微信二维码，可添加药时空小编请注明：姓名+研究方向！

DEERFIELD, Ill.--(BUSINESS WIRE)--Lundbeck US, the US subsidiaries of H. Lundbeck A/S, today announced it will present one oral and eight poster presentations at the 67th Annual Scientific Meeting of the American Headache Society (AHS) in Minneapolis from June 19-22, 2025. The data presentations reinforce the need to look beyond monthly migraine days (MMDs) and the importance of a holistic approach to migraine care as suggested by data from eptinezumab-jjmr post-hoc analyses. VYEPTI® (eptinezumab-jjmr) is indicated for the preventive treatment of migraine in adults. VYEPTI is contraindicated in patients with serious hypersensitivity to eptinezumab-jjmr or to any of its ingredients. Reactions have included anaphylaxis and angioedema. Please see Important Safety Information below. “Migraine disease affects over 40 million people in the U.S.,1 profoundly impacting every aspect of life for many,” said Damian Fiore, Vice President, Lundbeck US Medical Affairs Neurology. “Lundbeck is energized to be at AHS, driving conversations on how we can better understand the holistic burden of migraine and redefine how we approach care. Our focus goes beyond just alleviating individual symptoms—we are committed to improving the overall quality of life for people living with migraine disease.” Analyses presented at AHS from several studies including clinical trials and real-world research continue to focus on novel ways to assess VYEPTI and study results and advance preventive migraine care: P-341 : Eptinezumab Treatment was Associated with Longer Interictal Periods and Corresponding Larger Improvements in Quality of Life in Participants With Migraine for Whom 2-4 Prior Preventive Treatments had Failed: A Post Hoc Analysis of the DELIVER Trial: Individuals living with migraine who have longer periods of time between migraine attacks (interictal periods) may experience a reduced overall burden of migraine. A post-hoc analysis of the phase 3b DELIVER trial during weeks 1-12 (n=853) and weeks 1-24 (n=832) evaluated the association between the mean longest interictal period and improvements in patient-reported quality of life (QoL) outcomes. Results from this post-hoc analysis indicate the mean longest interictal period was larger with VYEPTI than as reported by patients receiving placebo during the first 24 weeks of the DELIVER trial. Among participants with >14- and >21-day mean longest interictal periods, a greater proportion of participants achieved clinically meaningful improvements in the 6-item Headache Impact test score (HIT-6; ≥5-point total score reduction) and Patient Global Impression of Change (PGIC; “much improved” or “very much improved” rating) with VYEPTI compared with placebo. 2 P-333 : Retention Rates Across Clinical Trials of Anti-CGRP Monoclonal Antibodies for Migraine Prevention : Researchers analyzed select phase 3 clinical trials to assess retention rates for adult participants who were treated with VYEPTI and other anti-CGRP mAbs for the prevention of migraine, including long-term eptinezumab trials: the 104-week, open label, single-arm PREVAIL trial and the 72-week DELIVER trial. In this retrospective cohort study of US claims data, VYEPTI showed high, long-term retention rates for preventive treatment in participants with chronic migraine and in those with migraine for whom 2-4 prior migraine preventive treatments have failed, suggesting a high level of participant satisfaction with continued treatment of VYEPTI. Similar results were observed in other anti-CGRP mAbs in this treatment group. 3 P-332 : Baseline Characteristics and Eptinezumab Infusion Experience in Participants in Whom ≥1 Prior Preventive Anti-CGRP Treatment Had Failed: Interim Results of an Ongoing Real-World Study : INFUSE is an ongoing, non-interventional, prospective study in individuals with migraine initiating VYEPTI for the preventive treatment of migraine. In an interim analysis of the first 75 participants entering the INFUSE study, results indicate that individuals, despite having ≥1 prior a-CGRP preventive treatment, reported a long history of disease and high disease burden (with regard to frequency, severity and cognitive impairments). Interim results also showed that the level of concern about initiating an intravenous (IV) treatment was low and participants in the study generally had a positive infusion experience. 4 Further highlighting our commitment to pushing the boundaries on migraine care with preventive treatments, Lundbeck also will host a symposium titled, “Why the interictal period matters: Striving for migraine freedom” with Dr. Amaal Starling and Dr. Stewart Tepper on Thursday, June 19 from 12:30 p.m. to 1:15 p.m. CT. “For optimal migraine management, it’s important to prioritize continuous improvement and a patient-centered approach,” said Dr. Amaal Starling, Neurologist, Mayo Clinic. “These studies highlight the real-world impact of preventive migraine treatments that can provide sustained control, which may allow individuals to focus on their personal goals and live their lives to the fullest.” Additional migraine data being presented at AHS include: IOR-02 (Oral) : Patient Perspectives of Migraine Symptomology: Insights from Exit Interviews from the anti-PACAP Antibody Phase 2 HOPE Trial for Migraine Prevention 5 P-299 : Associated Long-Term Clinical Improvements Following ≥50% Migraine Response and Sustained ≥50% and ≥75% Migraine Reductions in Early Responders to Eptinezumab Treatment in Participants With Migraine: Post Hoc Analyses of the DELIVER Trial 6 P-320 : Sustained Reductions in Monthly Headache Days with Long-Term Eptinezumab Treatment for Chronic Migraine: Post Hoc Analysis of the Phase 3 PREVAIL Study 7 P-319 : Impact of Participant-reported ≥75% Increase in Good Days/Month on Migraine Symptoms, Quality of Life, and Brain Fog: Results of the REVIEW Real-world Study of Adults With Chronic Migraine Treated with Eptinezumab 8 P-297 : Eptinezumab and Patient Education in Chronic Migraine and Medication-overuse Headache: Results from the Randomized, Placebo-controlled RESOLUTION Trial 9 P-308 : Efficacy and Safety of Eptinezumab in Chronic Migraine: A Randomized Placebo-controlled Trial in a Predominantly Asian Population 10 About VYEPTI® VYEPTI® (eptinezumab-jjmr) is a humanized monoclonal antibody that binds to calcitonin gene-related peptide (CGRP) ligand and blocks its binding to the receptor. VYEPTI was deliberately developed for administration by IV infusion to deliver 100 percent of the medication into the bloodstream at the end of the infusion. The efficacy and safety of VYEPTI were demonstrated in two phase 3 clinical trials; episodic migraine in PROMISE-1 and chronic migraine in PROMISE-2. VYEPTI met its primary endpoint of decrease in mean monthly migraine days (MMD) over months 1-3 in both episodic and chronic migraine. The safety of VYEPTI was evaluated in 2,076 patients with migraine who received at least one dose of VYEPTI. The most common adverse reactions (≥2 percent and at least 2 percent or greater than placebo) in the clinical trials for the preventive treatment of migraine were nasopharyngitis and hypersensitivity. In PROMISE-1 and PROMISE-2, 1.9 percent of patients treated with VYEPTI discontinued treatment due to adverse reactions. VYEPTI offers patients with migraine a preventive treatment administered as one 30-minute IV infusion 4 times a year (every three months). The recommended dosage is 100 mg, and some patients may benefit from a dosage of 300 mg. Dosing should be based on the guidance in the Prescribing Information and Patient Information. INDICATION VYEPTI (eptinezumab-jjmr) is indicated for the preventive treatment of migraine in adults. IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS VYEPTI is contraindicated in patients with serious hypersensitivity to eptinezumab-jjmr or to any of the excipients. Reactions have included anaphylaxis and angioedema. WARNINGS AND PRECAUTIONS Hypersensitivity Reactions: Hypersensitivity reactions, including angioedema, urticaria, facial flushing, dyspnea, and rash, have occurred with VYEPTI in clinical trials and in the postmarketing setting. Most hypersensitivity reactions occurred during infusion and were not serious, but often led to discontinuation or required treatment. Serious hypersensitivity reactions may occur. Cases of anaphylaxis have been reported in the postmarketing setting. If a hypersensitivity reaction occurs, consider discontinuing VYEPTI and institute appropriate therapy. Hypertension: Development of hypertension and worsening of pre-existing hypertension have been reported following the use of CGRP antagonists, including VYEPTI, in the postmarketing setting. Some of the patients who developed new-onset hypertension had risk factors for hypertension. There were cases requiring initiation of pharmacological treatment for hypertension, and in some cases hospitalization. Hypertension may occur at any time during treatment, but was most frequently reported within 7 days of therapy initiation. The CGRP antagonist was discontinued in many of the reported cases. Monitor patients treated with VYEPTI for new-onset hypertension or worsening of pre-existing hypertension, and consider whether discontinuation of VYEPTI is warranted if evaluation fails to establish an alternative etiology or blood pressure is inadequately controlled. Raynaud’s Phenomenon: Development of Raynaud’s phenomenon and recurrence or worsening of pre-existing Raynaud’s phenomenon have been reported in the postmarketing setting following the use of CGRP antagonists. In reported cases with monoclonal antibody CGRP antagonists, symptom onset occurred a median of 71 days following dosing. Many of the cases reported serious outcomes, including hospitalizations and disability, generally related to debilitating pain. In most reported cases, discontinuation of the CGRP antagonist resulted in resolution of symptoms. VYEPTI should be discontinued if signs or symptoms of Raynaud’s phenomenon develop, and patients should be evaluated by a healthcare provider if symptoms do not resolve. Patients with a history of Raynaud’s phenomenon should be monitored for, and informed about the possibility of, worsening or recurrence of signs and symptoms. ADVERSE REACTIONS The most common adverse reactions (≥2% and at least 2% or greater than placebo) in the clinical trials for the preventive treatment of migraine were nasopharyngitis and hypersensitivity. VYEPTI was approved by the U.S. Food and Drug Administration (FDA) for the preventive treatment of migraine in adults in February 2020. For more information, please see Full Prescribing Information and Patient Information or visit www.VYEPTIHCP.com. About Migraine Disease Migraine is a complex and disabling neurological disease that limits functionality and quality of life.1 It is characterized by moderate to severe head pain typically accompanied by an array of symptoms, including nausea, vomiting and sensitivity to light or sound.1,11 Over time, migraine disease may worsen, with attacks increasing in frequency, severity and duration.12,13 It is estimated to affect more than 40 million people in the U.S. and impacts three times as many women than men.1 It is the second leading cause of years lived with disability (YLD) among all diseases and is the top YLD cause among people aged 15 to 49 years, according to the Global Burden of Disease study. The impact of migraine permeates into career, home life and relationships.14 About INFUSE study INFUSE is an ongoing, non-interventional, prospective study in individuals with migraine, initiating preventive treatment with eptinezumab-jjmr. Eligible participants were recruited by two infusion center networks and are being followed for 12 months after initiating eptinezumab-jjmr treatment. INFUSE includes adults ≥18 years of age with a diagnosis of migraine who tried ≥1 preventive a-CGRP treatment (erenumab, fremanezumab, galcanezumab, atogepant, or rimegepant [prescribed every other day]). About DELIVER study DELIVER (NCT04418765) is a phase 3b, multicenter, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of eptinezumab-jjmr in patients with chronic or episodic migraine. Chronic migraine was defined as migraine occurring on ≥8 days per month and headache occurring on >14 days, and episodic migraine as migraine occurring on ≥4 days and headache occurring on ≤14 days. All patients had to have experienced failures of two to four prior preventive treatment classes (including: propranolol, metoprolol, topiramate, amitriptyline, flunarizine, valproate, divalproex, candesartan) or botulinum toxin A/B (if documented that botulinum toxin was used for chronic migraine), and at least one failure being due to inadequate efficacy. Patients who experienced failure on a previous treatment targeting the calcitonin gene-related peptide (CGRP) pathway were excluded from participation. Documented evidence of prior migraine treatment failures was supported by medical records or by physicians´ confirmation specific to each treatment in the past 10 years. In the study, 892 patients were randomized to receive eptinezumab-jjmr 100 mg or 300 mg or placebo by IV infusion. Patients included in the study most frequently experienced treatment failures of topiramate and amitriptyline, with 550(61.8%), 277(31.1%), and 60(6.7%) patients experiencing 2, 3, and 4 prior preventive treatment failures respectively. The primary endpoint was change from baseline in the number of monthly migraine days over Weeks 1-12. Key secondary endpoints included response rates as patients with 50% or greater reduction from baseline in MMDs (Weeks 1-12), response rates of patients with 75% or greater reduction from baseline in MMDs (Weeks 1-12) and change from baseline in the number of MMDs (Weeks 13-24). Other secondary endpoints assessed the effect of eptinezumab-jjmr vs placebo on: 6-item Headache Impact test score (HIT-6), Migraine-specific quality of life (MSQ v2.1), HRQoL (EQ-5D-5L) visual analogue scale (VAS) score, healthcare resources utilization (HCRU), and Work Productivity and Activity Impairment Questionnaire (WPAI). The safety and tolerability of eptinezumab-jjmr in the DELIVER study were similar to placebo and consistent with findings from previous eptinezumab-jjmr clinical trials. In DELIVER and earlier eptinezumab-jjmr studies, upper respiratory tract infection, nasopharyngitis, dizziness, and fatigue were the most commonly reported treatment-emergent adverse events (TEAEs). About PREVAIL study PREVAIL was a phase 3, open-label multi-site U.S.-based study that evaluated eptinezumab-jjmr 300 mg intravenous administration in 128 adults with chronic migraine (CM). PREVAIL included two treatment phases: the primary treatment phase included four infusions of eptinezumab-jjmr 12 weeks apart (Day 0, and Weeks 12, 24, and 36); the secondary treatment phase included up to four additional eptinezumab-jjmr infusions 12 weeks apart (Weeks 48, 60, 72, and 84). Further, patients were followed for 20 additional weeks after the final infusion until Week 104. The PREVAIL study evaluated the long-term safety of repeat doses of eptinezumab-jjmr 300 mg in patients with CM, as well as the pharmacokinetics, immunogenicity, and patient-reported outcomes (PROs). Patient-reported outcome measures included the Migraine Disability Assessment (MIDAS) questionnaire, patient-identified most bothersome symptom (PI-MBS) associated with migraine, Patient Global Impression of Change (PGIC), and 6-item Headache Impact Test (HIT-6). About a-PACAP a-PACAP monoclonal antibody is an investigational compound currently under development (phase 2) for the treatment of migraine. The compound is not commercially available globally. About Lundbeck Lundbeck is a global biopharmaceutical company focusing exclusively on brain health. With more than 70 years of experience in neuroscience, we are committed to improving the lives of people with neurological and psychiatric diseases. Brain disorders affect a large part of the world’s population, and the effects are felt throughout society. With the rapidly improving understanding of the biology of the brain, we hold ourselves accountable for advancing brain health by curiously exploring new opportunities for treatments. As a focused innovator, we strive for our research and development programs to tackle some of the most complex neurological challenges. We develop transformative medicines targeting people for whom there are few or no treatments available, expanding into neuro-specialty and neuro-rare from our strong legacy within psychiatry and neurology. We are committed to fighting stigma and we act to improve health equity. We strive to create long-term value for our shareholders by making positive contributions to patients, their families and society as a whole. Lundbeck has approximately 5,700 employees in more than 50 countries and our products are available in more than 80 countries. Lundbeck US comprises the wholly owned US subsidiaries of H. Lundbeck A/S (HLUNa / HLUNb, HLUNA DC / HLUNB DC) (“Lundbeck”), including Lundbeck LLC and Lundbeck Pharmaceuticals LLC. For additional information, please visit Lundbeck.com/us and connect with us on LinkedIn and X at @LundbeckUS. References 1 Cohen, F., Brooks, C. V., Sun, D., Buse, D. C., Reed, M. L., Fanning, K. M., & Lipton, R. B. (2024). Prevalence and burden of migraine in the United States: A systematic review. Headache, 64(5), 516–532. https://doi.org/10.1111/head.14709 2 Tepper, Stewart J., Joshi, Shivang, Hirman, Joe, et al. Eptinezumab Treatment was Associated with Longer Interictal Periods and Larger Improvements in Quality of Life in Participants With Migraine for Whom 2-4 Prior Preventive Treatments had Failed: A Post Hoc Analysis of the DELIVER Trial. Available at https://headachejournal.onlinelibrary.wiley.com/. Accessed June 4, 2025. 3 Blumenfeld, Andrew, Patel, Foram, Kapur, Neha, et al. Retention Rates Across Clinical Trials of Anti-CGRP Monoclonal Antibodies for Migraine Prevention. Available at https://headachejournal.onlinelibrary.wiley.com/. Accessed June 4, 2025. 4 Starling, Amaal, Regnier, Stephane, Soni-Brahmbhatt, Seema, et al. Characteristics and Eptinezumab Infusion Experience in Participants in Whom ≥1 Prior Preventive anti-CGRP Treatment had Failed: Interim Results of an Ongoing Real-world Study. Available at https://headachejournal.onlinelibrary.wiley.com/. Accessed June 4, 2025. 5 Lipton, Richard B., IOR-02 - Patient perspectives of migraine symptomology: Insights from exit interviews from the anti-PACAP antibody phase 2 HOPE trial for migraine prevention. Available at https://headachejournal.onlinelibrary.wiley.com/. Accessed June 4, 2025. 6 Ailani, Jessica, Ashina, Messoud, Awad, Susanne F., et al. Long-term Improvements Following ≥50% Migraine Response to Eptinezumab Treatment in Participants With Migraine: Post Hoc Analysis of the DELIVER Trial. Available at https://headachejournal.onlinelibrary.wiley.com/. Accessed June 4, 2025. 7 Starling, Amaal, Kudrow, David, Kapur, Neha, et al. Sustained Reductions in Monthly Headache Days with Long-Term Eptinezumab Treatment for Chronic Migraine: Post-Hoc Analysis of the Phase 3 PREVAIL Study. Available at https://headachejournal.onlinelibrary.wiley.com/. Accessed June 4, 2025. 8 Starling, Amaal, Kudrow, David, Kapur, Neha, et al. Sustained Reductions in Monthly Headache Days with Long-Term Eptinezumab Treatment for Chronic Migraine: Post-Hoc Analysis of the Phase 3 PREVAIL Study. Available at https://headachejournal.onlinelibrary.wiley.com/. Accessed June 4, 2025. 9 Jensen, Rigmor H., Lundqvist, Christofer, Schytz, Henrik W., et al. Eptinezumab and patient education in chronic migraine and medication-overuse headache: Results from the randomized, placebo-controlled RESOLUTION trial. Available at https://headachejournal.onlinelibrary.wiley.com/. Accessed June 13, 2025 10 Yu, Shengyuan, Matsumori, Yasuhiko, Kim, Byung-Kun, et al. Efficacy and safety of eptinezumab in chronic migraine: A randomized placebo-controlled trial in a predominantly Asian population. Available at https://headachejournal.onlinelibrary.wiley.com/. Accessed June 13, 2025. 11 National Institute of Neurological Disorders and Stroke. Migraine. Available at: https://www.ninds.nih.gov/health-information/disorders/migraine. Accessed March 28, 2024. 12 GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016 [published correction] appears in Lancet. 2017;390(10100):1211-1259. 13 American Headache Society. Headache. 2019; 59: 1–18. 14 Buse DC, Fanning KM, Reed ML, et al. Life With Migraine: Effects on Relationships, Career, and Finances From the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study. Headache. 2019;59(8):1286-1299. doi:  https://doi.org/10.1111/head.13613.