科睿唯安年度报告 2020 最值得关注的药物预测 1 科睿唯安发布 2020 最值得关注的药物预测年度报告，甄选出 11 种预 计于今年上市的重磅药物 . 3 The 2020 Cortellis Drugs to Watch. 7 1. 11 个潜在的重磅炸弹级药物迎来希望，同时面临 支付意愿的挑战 . 8 11 potential blockbuster drugs offer hope, threaten budgets . 10 2. 定价将在未来潜在重磅炸弹级药物的发展中扮演更重要的角色 . 14 Pricing could assume a larger role for would-be blockbusters . 17 3. 提升给药便利性，三款药物强势入局多发性硬化症和偏头痛领域 . 21 CNS drugs provide new delivery options, cleaner safety for MS and migraine . 29 4. 患者故事 : CGRP 疗法解救 Jaime Sanders 的顽固偏头痛 . 39 A patients perspective: Jaime Sanders finds relief with CGRP therapies . 41 5. 患者故事： Karen Jury 的多发性硬化症不再进展，但疲劳和药物费用 问题依然存在 . 43 A patients perspective: Karen Jurys MS progression halted, but fatigue, drug cost concerns persist . 45 6. Valrox 和 Vadadustat, 重塑血液疾病前景 . 47 Therapies poised to reshape the treatment landscape for hematologic disorders . 53 7. 从基础科学走出的“重磅炸弹”药物 Vadadustat . 60 Out of basic science, a blockbuster: Vadadustat . 61 8. Filgotinib，多种潜在适应症有望带来销售额攀升 . 62 Filgotinib looks to JAK up sales with multiple indications . 65 9. 三高家族的颠覆式产品 -Inclisiran 和 Rybelsus . 70 Novartis high steaks with inclisiran in FH; optimism for Rybelsus in diabetes . 75 10. 包容性研究收获科学和财富： Incisiran . 80 Inclusive research brings scientific, monetary riches: Inclisiran . 82 11. 抗体偶联药物的时代来了吗？ . 84 Is it finally their time? Two ADCs for cancer make the blockbuster list . 92 2 Cortellis 2020 最值得关注的药物预测年度报告的方法论 . 99 Methodology for the Cortellis Drugs to Watch 2020. 101 3 科睿唯安发布 2020 最值得关注的药物预测年度报告，甄选出 11 种预 计于今年上市的重磅药物 治疗高发性疾病的新药为大众带来希望 Cortellis 评选出极具商业价值和临床应用潜力的新药，主要集中在乳腺癌、恶性淋巴 瘤、多发性硬化症以及偏头痛等疾病领域 。 2020 年 2 月 10 日，费城 /伦敦 全球领先的专业信息服务提供商科睿唯安今天发布了 2020 最值得关注的药物预测年度报告，预测了 11 种将于 2020 年上市并且到 2024 年年销售额有望突破 10 亿美元的新药 (重磅药物 )。 科睿唯安的 Cortellis 团队运用其专有技术、工具和方法，从已在 2020 年初处于 II 期或 更高临床阶段的药物中甄选产生了一份潜力药物清单。团队分析师随后通过审查清单中每 个药物的年度申报文件、管线信息、临床试验、专利情况、化学、交易记录、会议、企业 公告以及法规状态等信息，逐一对入选药物进行专项研究和评估 。 今年，业界知名的生物医药通讯 BioWorld 的编辑和记者，通过全方位检视多种疾病概 览，分析药物定价策略，探询新药的科学原理来审视这些将于 2020 年上市的药物最终能 否为患者和开发者们带来福音 。 值得关注的药物主要集中在慢性、进展性疾病领域，包括针对乳腺癌、多发性硬化症 (MS)、偏头痛和 2 型糖尿病的药物 。 孤儿药制度和其他资格认证几乎对入选清单的所有药物研发均起到了加速作用。尽管清单 上的大部分药物即将或准备进入的市场已经充斥着众多竞争产品，他们在市场表现也将面 临巨大压力，但是预测团队对入选药物的商业前景依旧抱有很高的期望。相对现有疗法， 许多新药预计会 展现更好的安全性，尤其对于心血管风险，而另一部分药物则会突出全新 的作用机制甚至是治愈潜力 。 清单上超过半数的药物是生物制剂，这是一种发展迅速且价格日益昂贵的处方药门类。近 年来，监管机构和支付方都试图控制生物制剂带来的高额支付成本。今年的药物清单上， 基因和细胞疗法的代表分别是比奥马林制药公司（ Biomarin）推出的甲型血友病治疗药 物 Valrox 和百时美施贵宝公司推出的大 B 细胞淋巴瘤治疗药物 lisocabtagene maraleucel，这两种药物都因奇高的价格而备受关注。一旦获得批准， Valrox 将成为 严 重甲型血友病的第一种潜在治愈药物。通过纠正导致血友病的遗传缺陷， Valrox 是一款 能一次性治愈患者的革命性药物，不再需要输血和凝血因子 VIII 置换。如果 Valrox 如期 率先推出，它将成为有史以来最昂贵的上市药物，每个疗程需 250 万美元至 300 万美元 费用 。 BioWorld 新闻部主任林恩 约菲（ Lynn Yoffee）说： “ 尽管科学创新、商业动机和公共 利益之间有时存在冲突，但随着医学研究和创新药物研发步伐的加快，这些药物的成功将 4 给更多人带来希望（如果负担得起），并且为开发者在提供创新机制和治愈潜力的同时带 来经济效益。 ” 前瞻性陈 述 本新闻稿以及针对新闻稿中的信息所做的口头陈述中可能包含有关科睿唯安的前瞻性陈 述。前瞻性陈述仅为科睿唯安对未来事件所做的当前预期或预测，可能包括有关预期协同 效应及其它未来预期的陈述。这些陈述涉及风险和不确定性，包括不受科睿唯安控制的因 素，可能导致实际结果与预期存在重大差异。无论是出现新信息、发生未 来事件亦或其它 情况，科睿唯安均无义务更新或修订此处所做之陈述 。 科睿唯安及其徽标，以及本文使用的所有其他商标均为其各自所有者的商标，并在获得许 可的情况下使用 。 5 Medicines that Treat High Prevalence Conditions Offer Hope to Many as the Annual Drugs to Watch List from Clarivate Identifies 11 New Blockbusters Forecasted to Launch in 2020 Cortellis identifies new drugs for treating indications for breast cancer, lymphoma, multiple sclerosis (MS) and migraine touted for commercial and clinical success PHILADELPHIA CCC.WS), a global leader in providing trusted insights and analytics to accelerate the pace of innovation, today announced the launch of its annual Cortellis “Drugs to Watch list, which identifies 11 new drugs scheduled to enter the market in 2020 predicted to achieve annual sales of $1 billion or more (i.e., blockbuster status) by 2024. The Cortellis team at Clarivate Analytics has applied its proprietary technologies, tools and techniques, to produce the list of potential drugs for inclusion from drugs that advanced to phase II trials or beyond in early 2020. Each drug was subsequently scrutinized by in-house analysts - researched and evaluated in its individual context by interrogating annual filings, drug pipelines, clinical trials, patents, chemistry, deals, conferences and company announcements and regulatory status. This year, editors and writers from award-winning life sciences news service BioWorld have examined the various disease landscapes from all angles, analyzed the pricing strategies, explored the science underpinning the new medicines to provide reality checks via the ultimate test: patients and advocacy groups who will seek beneficiary outcomes from the new drugs entering the market in 2020. The list and corresponding analyses focus on the treatment and possible cure for chronic, progressive and often debilitating diseases and conditions, including drugs which target the indications of breast cancer, multiple sclerosis (MS), migraine and type 2 diabetes. The drugs listed have been almost universally accelerated in their development by orphan drug status or other designation intended to speed their path to market. There is a high level of expectation of commercial success for each of these drugs - despite the fact that most medicines on the list are entering or are poised to enter markets already crowded with competitors, meaning theyll face substantial pressures to differentiate themselves. Many are expected to tout improved safety vs. alternative therapies, especially regarding cardiovascular risk, while others will seek to highlight novel mechanisms of action or even curative potential. 6 More than half of the medicines on the list are biologics, a fast-growing and increasingly expensive segment of prescription medicines for which regulators and payers alike have sought to rein in costs during recent years. Gene and cell therapies represented on this years list by hemophilia A therapy Valrox (Biomarin Pharmaceutical, Inc.) and lisocabtagene maraleucel (Bristol-Myers Squibb Co) for large B-cell lymphoma, respectively have drawn particular attention for their high costs. If approved, Valrox will be crowned as the first potential curative approach for severe hemophilia A. The one-and-done therapy will be transformative as it corrects the genetic defect underlying the condition and eliminates the need for blood transfusions and FVIII replacement therapy. If, as expected it takes a leadership position it could become the most expensive drug ever to reach the market with a cost of $2.5 million $3 million per treatment. Lynn Yoffee, News Director, BioWorld, “Despite the ongoing tension among scientific innovation, commercial motive and public good, as medical research and the pursuit of innovative medicines continues to accelerate, the success of these drugs will bring hope to many if they can afford them - and seek to provide the benefits of novel mechanisms of action alongside curative potential.” The full list and analysis are freely available online at: 7 The 2020 Cortellis Drugs to Watch 8 1. 11 个潜在的重磅炸弹级药物迎来希望，同时面临支付意愿的挑战 原文作者： Michael Fitzhugh and Joan Tur 中文翻译：梅馨 有望治愈重症甲型血友病的潜在基因疗法 Valrox（ valoctocogene roxaparvovec）将成 为有史以来最昂贵的药物，新名单上的 11 种新药有望在 2024 年底甚至更早就达成 10 亿美元以上的年销售额，这将进一步突显医疗创新和社会支付能力之间日益紧张的关系。 2020 Cortellis Drug to watch (包括已批准和可能批准的药物 )指出，在根本性分歧 的推动下，支付方与制药行业间的冲突仍将持续。 由科睿唯安的 Cortellis 团队预测分析，这份名单上癌症治疗药物占大多数。 几乎像达成 共识一样地，这些药物的开发均获得了加速，要么是通过孤儿资格认定，要么是为促进药 物监管机构与开发者之间更紧密合作以造福患者。这 11 种可能成为重磅炸弹的药物共拥 有 18 个孤儿药资格认定，四个 FDA 突破性疗法认定，两个 EU PRIME 指定和一个日本 SAKIGAKE 指定。 入选 Cortellis 评估分析范畴的药物包括在 2020 年初就已进入 II 期临床试验或者更后 期，但排除 2020 年前就已上市的药物。 根据研发公司预期的批准日期或上市日期，这 些名单上未获批的药物有望在 2020 年获批上市。 名单上的大多数药物 正在开发或即将进入的是已挤满竞争对手的适应症，这意味着它们将 面临说明自己与众不同的巨大压力。预计多数进榜的药物将强调自己与其它疗法相比将提 高安全性，特别是围绕心血管风险，还有一些则强调新的作用机制，甚至是治愈疾病的潜 力。 Rybelsus（口服 semaglutide）和 Enhertu（曲妥珠单抗 deruxtecan）这两种药物已获 得美国监管部门的批准，每种都预示着独具意义的创新性，以证明它们对患者和支付方的 潜在价值。来自诺和诺德的 Rybelsus 是首款针对 2 型糖尿病患者的口服胰高血糖素样肽 1 受体激动剂，以 更为方便的每日一片的方式达到了迄今为止只能通过注射给药的疗效。 第一三共和阿斯利康联合开发的 Enhertu 比预期提前了数月获批，为某些乳腺肿瘤提供 了新的治疗方法，它的开发是建立在另一个重磅炸弹级药物 -赫赛汀之上，自 1998 年获 批以来医学对这类疾病的认知及进展。 名单上半数以上的药物为生物制剂，这是处方药中一个快速增长且日益昂贵的领域，近年 来监管部门和支付方采用了不同方法试图控制成本。基因疗法和细胞疗法，分别以甲型血 友病治疗药物 Valrox（ valoctocogene roxaparvovec）（由 Biomarin 制药研发）和大 B 细胞淋巴瘤治疗药物 lisocabtagene maraleucel（由百时美施贵宝研发）为代表，均 因可能远超预算而备受关注，尤其是有诺华 Zolgensma（ onasemnogene abeparvovec）的先例。 2019 年获批的 Zolgensma 可用于罕见的遗传性疾病脊髓性肌 9 萎缩症的治疗，价格令人瞠目。 Zolgensma 曾被列入 2019Cortellis Drug to watch， Zolgensma 于 2019 年 5 月首次亮相，批发采购价约为 210 万美元。 尽管欢迎创新的生物制剂，但监管部门还在鼓励生物类似物对同类老产品进行更充分的价 格竞争（生物类似物是被公认的与已批准的原研生物制剂高度相似的药物）。 这类挑战 者可能会对今年的 2020 Cortellis Drug to watch上的一些在列药物构成不利影响， 包括用于多发性硬化症的 ozanimod（由百时美施贵宝研发）及用于类风湿性关节炎的 filgotinib（由 Galapagos NV 和吉利德联合研发）。 尽管公众对美国处方药价格感到愤慨，政府也为解决这一问题做出了政治努力，例如出台 降低药品成本立即法案，但在华盛顿，党派分歧严重，一群热衷于维持现状的不透明 的参与者持续阻碍着法案的推行。与此同时，美国在评估药品价值及其成本方面所做的努 力经常遭到制药商的敌视，制药商对其他主要市场的发展持谨慎态度，这些其他主要市场 的政府已施加压力，让制药商无法获得他们通常能在美国获得的利润。 今 年的 2020 Cortellis Drug to watch有 11 种药物，在数量上多于去年的 7 种，并 且包含了更多的“ first-in-class” 药物。 Biohaven 制药的偏头痛药物（ BHV-3000）有 望成为首个用于急性偏头痛治疗的小分子 CGRP 拮抗剂。 Valrox 如果获批将成为治疗任 何形式血友病的首个基因疗法。来自 The Medicines 公司（最近被诺华收购）的 Inclisiran 可能成为首个获批的基于 siRNA 的 PCSK9 抑制剂。 Immunomedics 公司的 sacituzumab govitecan 有望成为第一个靶向泛上皮癌抗原 TROP-2 的 ADC 药物。 回顾去年名单，作为去年名单上唯一的“ first-in-class”药物 Palforzia，它突显出每种 药物进入市场路径微小差别的重要性， Aimmune 制药的 Palforzia 直到 2020 年 1 月 31 日才获得批准，预计到 2024 年销售额才会超过 10 亿美元，比之前的预期晚一年。 2019 年同样上榜的其他药物也面临上市后的销售差异，如用于预防遗传性血管性水肿的 Takhzyro（ lanadelumab）（由武田制药研发 ）上市后面临销售停滞不前 ; 同时间也有如 甲型血友病的治疗药物 Hemlibra（ emicizumab）（由罗氏研发）销售一路颷升。 不管今年名单上的药物命运如何，随着医学研究及对创新药物的追求的不断加速，在未来 一年里，科学创新、商业动机和公共药物之间的矛盾很可能会继续成为人们关注的焦点。 10 11 potential blockbuster drugs offer hope, threaten budgets By Michael Fitzhugh and Joan Tur Crowned by a potential cure for severe hemophilia A, that could become the most expensive drug ever, a new list of 11 medicines expected to generate $1 billion-plus in annual sales by the end of 2024 or earlier throws into stark relief the growing tension between medical innovation and societys ability to pay for it. The 2020 Cortellis Drugs to Watch list, including medicines both approved and likely to be, points to a future of ongoing conflict between payers and industry spurred by fundamental disagreements. Drugs for central nervous system indications and cancer comprise much of the list, developed by Clarivate Analytics Cortellis forecast team. Almost universally, they have been accelerated in their development by orphan drug status or other designations intended to spur closer cooperation between regulators and drug developers with the intention of speeding their availability for patients. The 11 likely blockbusters identified collectively hold 18 orphan drug designations, four FDA breakthrough therapy designations, two EU PRIME designations and a Japanese SAKIGAKE designation. Drugs considered in the analysis had advanced to phase II trials or beyond by early 2020. Medicines launched prior to 2020 were excluded. Listed drugs that are not yet approved are expected to go to market in 2020, based on factors such as companies expected approval or launch dates. Most medicines on the list are entering or are poised to enter indications already crowded with competitors, meaning theyll face substantial pressures to differentiate themselves. Many are expected to tout improved safety vs. alternative therapies, especially around cardiovascular risk, while others will seek to highlight novel mechanisms of action or even curative potential. Two of the medicines, Rybelsus (oral semaglutide) and Enhertu (trastuzumab deruxtecan) have already won U.S. regulatory approvals, each heralding significant new innovations to justify their potential value to patients and payers. Rybelsus, from Novo Nordisk A/S, represents the first oral glucagon-like peptide- 1 receptor agonist for people with type 2 diabetes, capturing the benefits of a medicine that had until now only been available as an injectable medicine in a more convenient once-daily tablet. Enhertu, a medicine from Daiichi Sankyo Co. Ltd. and Astrazeneca plc approved months ahead of expectations, delivered a new method for targeting certain breast tumors, building on the many advances in medicines understanding of the diseases since the approval of another blockbuster, Herceptin (trastuzumab, Roche Holding AG) in 1998. 11 More than half the medicines on the list are biologics, a fast-growing and increasingly expensive segment of prescription medicine for which regulators and payers alike have sought to rein in costs during recent years, albeit with differing approaches. Gene and cell therapies represented on this years list by hemophilia A therapy Valrox (valoctocogene roxaparvovec, Biomarin Pharmaceutical Inc.) and lisocabtagene maraleucel (Bristol-Myers Squibb Co.) for large B-cell lymphoma, respectively have drawn particular attention for their budget-busting potential, especially in the wake of 2019s eye-opening price for Zolgensma (onasemnogene abeparvovec), a therapy for the rare genetic disease spinal muscular atrophy. Featured on the 2019 Cortellis Drugs to Watch list, Zolgensma debuted in May 2019 with wholesale acquisition cost of about $2.1 million. Though welcoming innovative biologics, regulators have also sought to encourage greater price competition for older products in the class from biosimilars. Biosimilars are medicines deemed to be highly similar to a reference biologic already approved. Such challengers could pose headwinds for several entrants on this years Cortellis Drugs to Watch list, including ozanimod for multiple sclerosis (Bristol-Myers Squibb Co.) and filgotinib for rheumatoid arthritis (Galapagos NV and Gilead Sciences Inc.) Despite public outrage over prescription drug prices in the U.S. and political efforts to address it, such as the Lower Drug Costs Now Act (H.R. 3), bitter partisan divides in Washington an often-opaque mix of players keen to protect the status quo continue to stand in the way of progress. Meanwhile, American efforts to assess the value of medicines vs. their cost have often met with hostility from drugmakers wary of developments in other major markets, where governments have pressured their ability to reap the kind of profits they often seek in the U.S. With 11 entrants, this years Cortellis Drugs to Watch list is both numerically longer than last years seven-drug list and includes more first-in-class medicines. Biohaven Pharmaceutical Holding Co. Ltd.s rimegepant (BHV -3000) for migraine is positioned to become the first small molecule CGRP antagonist to launch for acute treatment of migraine. Valrox, if approved, would become the first gene therapy for any form of hemophilia. Inclisiran, from The Medicines Co. (recently acquired by Novartis AG), could become the first siRNA-based inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) to win approval. And Immunomedics Inc.s sacituzumab govitecan is poised become the first antibody - drug conjugate to target TROP-2, a pan-epithelial cancer antigen. Highlighting the importance of even small deviations in each drugs path to market, last years sole first-in-class medicine on the list, Aimmune Therapeutics Palforzia (peanut), was