Suzetrigine

注：本文不构成任何投资意见和建议，以官方/公司公告为准；本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及），不代表平台立场。任何文章转载需得到授权。在生物医药的浩瀚星海中，小分子药物以其独特的穿透力和便捷性，持续在大分子药物的快速发展浪潮中稳居半壁江山。药融咨询最新发布的《2024年十大重磅小分子药物》报告，为我们揭示了即将在市场上大放异彩的十款小分子药物，它们不仅在治疗领域具有创新性，更以其巨大的市场潜力，成为投资者和业内人士关注的焦点。 01全球获批和销售额TOP100占比情况：小分子创新药仍占据半壁江山近五年，美国FDA批准的新药以小分子化学药为主，2019-2023年占比分别为65%、62%、56%、46%、55%，获批生物制品占比逐渐提升，从2019年的15%提升至2023年的31%。2023年，美国FDA共批准55款新药上市，其中小分子药物共30款，占比约55%；从疾病领域来看，小分子新药多集中在肿瘤和罕见病领域，其次为免疫炎症、感染、神经系统、心血管及代谢类疾病。数据来源：FDA，各企业财报，药融咨询整理2023年全球药品销售额TOP100榜单中，共有45款小分子药物上榜，数量占比位列第一，实现销售额约1758.71亿美元，销售金额占比约38%。排名前三的小分子药物分别是BMS/辉瑞的阿哌沙班、吉利德的必妥维、BI/礼来的恩格列净。2023年全球药品销售额TOP100榜单（亿美元）数据来源：各企业财报，药融咨询整理（灰色为小分子） 022024年十大重磅小分子药物概览药融咨询综合药融云数据库、医药投融资、专利信息及行业权威数据，从进度、创新性和市场前景三个关键维度，精选出2024年备受瞩目的十大小分子药物。这些药物或正处于注册至批准阶段，或为特定治疗领域的机制创新，且市场潜力巨大，预计销售额峰值均达到10亿美元以上。数据来源：FDA、各公司官网、药融咨询整理 01小分子药物ResmetiromResmetirom作为全球首款NASH疗法，靶向甲状腺激素受体β亚型。是由Madrigal公司开发的一款高选择性的甲状腺激素受体β（THR-β）激动剂，能被肝脏特异性摄取，激活肝脏中高表达的THR-β，促进脂肪分解，降低低密度胆固醇、甘油三酯和其它致动脉粥样硬化脂蛋白水平，减少肝脏脂肪堆积，改善肝脏功能，从而治疗非酒精性脂肪性肝炎（ NASH ）。数据来源：Madrigal公司官网，药融咨询整理2024年3月15日，美国FDA加速批准Resmetirom上市，用于治疗中重度肝纤维化的非肝硬化NASH/代谢功能障碍相关脂肪性肝炎（MASH）成人患者，这是FDA批准的首款治疗NASH的药物。数据来源：药融云全球药物研发数据库 临床试验成果显著，FDA提出的两个主要终点Madrigal/Resmetirom：临床数据优异，III期临床达到FDA提出的两个主要终点。主要终点（ NASH缓解且无纤维化进展）：Resmetirom组NASH缓解且无纤维化进展的受试者比例显著高于安慰剂组（80mg组，100 mg组和安慰剂组受试者比例分别为25.9%，29.9%和9.7%，组间差异有统计学意义）。主要终点（纤维化改善同时NAS评分无恶化）：纤维化缓解至少1期且NAS评分没有加重的受试者比例也显著高于安慰剂组（80 mg组，100 mg组和安慰剂组受试者比例分别为24.2%，25.9%和14.2%，组间差异有统计学意义）。数据来源：[1]A phase 3, randomized, controlled trial of resmetirom in NASH with liver fibrosis[J]. New England Journal of Medicine, 2024, 390(6): 497-509.，药融咨询整理。 NASH患者众多，全球药市将破百亿美金患病率高：全球NAFLD的患病率大约在25%-30%左右，各个地区因诊断，种族和地理区域而异；亚洲地区的患病率为27%，中国的患病率为29.8%，高于北美（24%）以及欧洲（24%）；NASH在普通人群中的患病率较难确定，有研究显示，经肝组织活检诊断的NASH在NAFLD人群中的总患病率为59.1%。数据来源：[1]Modeling nafld disease burden in china, france, germany, italy, japan, spain, united kingdom, and united states for the period 2016–2030[J]. Journal of hepatology, 2018, 69(4): 896-904.，药融咨询整理全球NASH患者人群基数较大：有研究预测至2030年中国NASH患者将由2016年的3260万人增长至4830万人，增长率为48%；美国NASH患者人数也将增长至2700万人。全球NAFLD/NASH市场持续增长：有数据显示2016-2020年全球NASH市场由17亿美元增长至19亿美元，复合年增长率为3.2%；预计至2025年达到107亿美元，并于2030年达到322亿美元，期间复合年增长率分别为41.8%和24.6%。竞争格局好，销售峰值有望达到55亿美元辉瑞、诺华、礼来、BMS、强生、诺和诺德等多个头部药企在NASH治疗领域布局多个临床项目；Inventiva、Akero、Madrigal 等代表企业的药物也取得了积极进展。据药融云数据库统计，全球处于临床Ⅲ期的管线不到10个，Resmetirom获批上市后有望快速占领NASH市场，Evercore ISI分析师估计，凭借NASH适应症，2030年Resmetirom全球销售额可能达到26亿美元，峰值可能达到55亿美元。数据来源：药融云数据库，药融咨询整理 02小分子药物VX-548VX-548一款Nav1.8抑制剂，Nav1.8是一种特定的离子通道蛋白，主要在神经组织中表达。它在感觉神经元中起着重要作用，参与传导疼痛信号和温度感知。抑制Nav1.8通道活性可以阻断疼痛信号的传导、减轻疼痛感觉并产生镇痛效应，同时Nav1.8不参与中枢神经相关的活动，不会存在类似阿片类药物的成瘾性问题，也不会对运动功能产生影响。数据来源：药融咨询整理 全球疼痛市场需求巨大，主流药物仍为阿片类和NSAIDs全球疼痛行业市场巨大，根据Mordor intelligence调查显示，2021年全球疼痛管理市场价值794亿美元，预计到2027 年将增长至1207亿美元，复合年增长率为7.39%。数据来源：Mordor intelligence、《中国疼痛医学发展报告(2020)》、药融云数据库、药融咨询整理《中国疼痛医学发展报告(2020)》显示，我国慢性疼痛病人数量超过3亿，并正以每年1000万至2000万的速度增长。药融云数据显示，中国镇痛类药物的市场规模已从 2016年的 133亿元增长至 2023Q1-3年的203亿元。2023年前三季度全国院端销售额TOP10的品种中阿片类有6款：地佐辛、布托啡诺、纳布啡、羟考酮、氢吗啡酮、喷他佐辛；3款NSAIDs：阿司匹林、丙帕他莫、赖氨匹林（Aspirin/lysine）；中成药一款：天麻素。 阿片类药物滥用成灾，20多年首款新机制镇痛药，峰值有望超50亿美元美国人口只占全球的5%，消耗的阿片类药物却占全球的80%（原本作为重症疼痛的镇痛药，滥用具备成瘾性）。美国CDC网站数字显示，在最近三次药物滥用危机中，即从1999年到2017年，阿片类药物已导致39.9万人死亡。市场一直在探索研发新型机制的镇痛药物，不仅要求能够媲美阿片类药物的镇痛效果，而且强调安全性和非成瘾性。福泰制药的小分子NaV1.8抑制剂VX-548为20多年来首款新机制的镇痛药，Leerink Partners分析师也预计到2030年VX-548的年销售额可能会达到51亿美元。2024年1月30日晚，福泰制药公布VX-548治疗中、重度急性疼痛最新三期数据，相比安慰剂组，VX-548治疗组达到了数字疼痛评分（NPRS）和48小时内疼痛强度差异的时间加权总和评分（SPID48）主要终点，同时VX-548安全性和耐受性良好，副作用发生率较安慰剂组更低。目前全球NaV1.8抑制剂研发管线 并不多，研发难度大，辉瑞，雅培， Vertex均陆续折戟。Vertex 最新一代抑制剂VX-548，是目前 全球进度最快且唯一III期临床成 功的NaV1.8抑制剂。数据来源：CDC、Leerink Partners、福泰制药、药融咨询整理版权声明：本文转自药融云 ，如不希望被转载的媒体或个人可与我们联系，我们将立即删除 活动推荐  8月 • NDC2024生物医药创新者峰会  关键词：  小分子，XDC，多肽及GLP-1热点话题，200+行业专家（点击扫码报名）▼【关于药融圈】药融圈PRHub旨在帮助生物医药科技型企业进行品牌推广及商务拓展服务，针对客户的真实需求制定系统化解决方案，通过“翻译-降维-场景化”将客户的品牌信息以直白易懂的方式被公众知悉，同时在流量渠道覆盖100万+垂直用户基础上实现合作目的，帮助合作伙伴完成从品牌开始到商务为终的闭环营销服务。我们已经完成了数十场线下1000人规模的生物医药研发类会议，涵盖小分子新药，大分子新药，改良型新药，BD跨境交易等多个领域，服务了百余家上市/独角兽/生物技术/制药企业。

Building with purple growth arrows/Nicole Bean for BioSpace The top 20 biopharma companies by revenue all bring in well over $10 billion dollars annually. Topping the list in 2023 was Johnson & Johnson, with a grand total just north of $85 billion in sales. Last week, AstraZeneca—which ranked in the top 10 last year with nearly $46 billion in revenue—announced that it is targeting the $80 billion mark by 2030. While there is no official definition of Big Pharma, these companies are no doubt it. So are Pfizer and Eli Lilly and Merck and Roche, among others. And it’s not just because of their revenue. A firm’s global presence is also important, Hartaj Singh, managing director and biotechnology analyst at Oppenheimer Holdings, told BioSpace. “Most pharma companies are what you call a multinational company,” Singh said. “Pfizer is presently [in] 150 countries; J&J, 175-plus.” However you consider Big Pharma, there are smaller biopharma firms that are jostling for a position among those ranks. Nicholas Schmitz, senior analyst at KBI Biopharma, identified several companies as emerging big pharma, including Regeneron and Vertex, plus big COVID-19 players BioNTech and Moderna. Similarly, Singh pointed to Vertex and Moderna. All of these companies bring in billions of dollars every year, and most have cracked GlobalData’s list of top 20 biopharma companies by market cap in Q1 2024. Gilead, Regeneron and Vertex all push or exceed $100 billion in this statistic, on par with GSK and Bristol Myers Squibb and not far behind Amgen, Sanofi and Pfizer. In addition to revenue, market cap and geographic presence, Schmitz noted that other factors can help propel smaller biopharma firms into the elite group of Big Pharma, including product portfolio breadth, the ability to influence health policy and pricing and the capacity to “have pivotal roles in addressing global health crises.” Big Pharma Through the Centuries The term Big Pharma is thought to have originated in the 1990s, possibly in a 1993 San Francisco Examiner article describing the “giant drug companies” that were striking up partnerships with smaller, younger biotechnology firms. Since then, the term has been used colloquially to describe the entire pharmaceutical industry or just a handful of the largest players. J&J, Eli Lilly, Pfizer, Merck and Roche can be thought of as the old big guns. These five companies and a handful of other undeniably big pharmaceutical companies were founded in the 1800s. These companies largely established their influence by allying with universities and medical associations to grow research efforts and the biomedical workforce. A handful of others climbed the ranks late in the 20th century and into the 21st. AbbVie was arguably the latest addition to the core Big Pharma list, launching in 2013 as a spinoff from Abbott Laboratories. One quality that applies to all Big Pharma firms is an international presence, but the form that takes will vary by company. Singh noted that companies focused on pharmaceutical products often go “high volume, lower price,” allowing them to expand their reach in developing countries, while biotechnology-focused companies may go “low volume, high price” and end up concentrated in countries that can afford more expensive drugs. “Amgen and Gilead probably have the largest amount of U.S. sales [among biotechnology companies]. Their sales are about 35% [in the U.S.] and the vast majority are in Europe,” Singh said. “On the other hand . . . pharma companies like AstraZeneca have sales of like 55% outside the U.S. and 45% in the U.S.” Biopharma Companies on the Rise Like other biotech companies, Vertex has made strides in the rare disease space. Four of its five approved drugs are used in cystic fibrosis, and the company estimates it can reach nearly 100,000 CF patients, according to its 2024 J.P. Morgan Healthcare Conference presentation. But the company also has broader goals: reaching the 90 million people impacted by acute and neuropathic pain. “They’ve got a focus on pain . . . and by changing the paradigm in pain they could become analogous to a pharma company in that they’ll be treating hundreds of thousands if not millions of patients,” Singh said. In the company’s Q1 finance presentation, it highlighted the potential of its clinical-stage drug suzetrigine “to fundamentally reshape the treatment of acute pain in the U.S.” Scientific strategy and understanding “the underlying biological rationale” are also key to a company’s growth, according to Singh. Vertex is an example of that. It follows the rational drug design philosophy, which focuses on specific biological targets that are validated in human health upfront. In 2023, Vertex brought in nearly $10 billion. Then in Q1 2024, the company reported a 13% year-over-year increase in product revenue and higher-than-predicted earnings per share in the first quarter of 2024. Many of the largest pharmaceutical companies have strategically acquired other companies to expand their portfolios, and Vertex has done the same. It acquired Alpine in April for $4.9 billion. Other companies identified as climbing the biopharma ranks have also toed or surpassed the $10 billion revenue mark in recent years. BioNTech, Regeneron and Moderna had large spikes in revenue in 2021 following the declaration of the COVID-19 pandemic, bringing in approximately $20 billion, $16 billion and $18 billion, respectively. BioNTech and Moderna both had roles in developing COVID-19 vaccines, and Regeneron developed one of the major antibody treatments. Of the three, Regeneron was the only one still above the $10 billion threshold in 2023, while BioNTech and Moderna saw significant declines. BioNTech saw a particularly sharp drop in revenue in the first quarter of 2024. However, Singh views Moderna as an important player because of its role in innovation with regard to mRNA and liquid nanoparticle technology. “Antibodies were just entering the commercial mainstream in the late 90s, and Amgen and Regeneron were basically viewed as the antibody companies, and maybe Genentech also,” Singh said. “What I’m seeing with Moderna, and to a lesser extent BioNTech, is a very similar kind of story.” Both companies saw U.S. stock prices increase in late May with H5N1 fears, according to the Wall Street Journal. Oppenheimer Holdings projected that private investment will “start catching up” and there will be more mRNA companies and drugs in the future, Singh noted. On the other hand, Gilead Sciences crossed the $10 billion revenue threshold back in 2013, and the company more than doubled that amount the following year. It is located in 35 countries per its 2024 Q1 SEC filings and continues to expand its portfolio. Overall, as the biopharma market continues to grow and new companies enter the fray, it remains to be seen which companies will expand their influence and become household names. Nadia Bey is a freelance reporter from North Carolina. Her work and contact information can be found at nadiabey.com