CSPC Pharmaceutical Group Ltd.

编者按：本文来自米内网，作者苍穹；赛柏蓝授权转载，编辑相宜 随着各大跨国药企财报披露，2024年全球畅销药TOP10基本尘埃落定。 据梳理，帕博利珠单抗全球销售额超294亿美元，蝉联“药王”宝座；降糖、减肥双雄司美格鲁肽及替尔泊肽保持高增长，携手迈入榜单前四；“自免”领域打得火热，实力选手度普利尤单抗位次再攀升，潜力新秀利生奇珠单抗首破100亿美元，昔日霸主修美乐跌落神坛；抗凝老将阿哌沙班坚守TOP3之位，但中国市场受集采及仿制药冲击，艾乐妥市场份额被进一步挤压。 01 畅销药TOP10门槛提升 自免“霸主”跌落神坛 随着各大跨国药企2024年业绩报告的公布，2024年全球畅销药TOP10也随之出炉。与此同时，笔者也附上2023年全球畅销药TOP10名单，能更直观地观察上榜药品的销售额、排名变化等情况。2024年全球畅销药TOP10（单位：亿美元）注：标红为预测值2023年全球畅销药TOP10（单位：亿美元）对比发现，2024年全球畅销药产品TOP1销售额约294亿美元，产品TOP10销售额门槛约102亿美元，相较于2023年（产品TOP1销售额约250亿美元，产品TOP10销售额门槛约100亿美元）均有所提升。具体产品排名上，可瑞达（帕博利珠单抗，俗称：K药）、Ozempic+Rybelsus+Wegovy（司美格鲁肽）、艾乐妥（阿哌沙班）依旧稳当牢固，继续包揽榜单前三；穆峰达（替尔泊肽）及达必妥（度普利尤单抗）增长迅猛，相继攀升至第四和第五位；必妥维（比克替拉韦+恩曲他滨+富马酸丙酚替诺福韦）、喜达诺（乌司奴单抗）表现稳定，分别位居TOP6和TOP9；新力军——Skyrizi（利生奇珠单抗）、兆珂（达雷妥尤单抗）及Trikafta（艾乐卡夫特+替沙卡夫特+伊伐卡夫特）凭借“过硬”的疗效首度挺进榜单，先后排在第七、第八和第十。此外，曾经的自免领域“药王”修美乐（阿达木单抗），面对生物类似药的大量涌入，首次跌出全球畅销药TOP10之列；步入疫情常态化时代，Comirnaty（mRNA疫苗）等新冠药物热度的消退亦是大势所趋...... 02 药王蝉联：K药的传奇之路 继2023年，默沙东的可瑞达又一次摘下2024年全球畅销药桂冠，销售收入高达294.82亿美元，再度创下本产品销售额新高。K药亮眼的销售成绩，与其在肿瘤治疗领域的领导地位密不可分。数据显示，目前该药已有超过40项适应症获批，覆盖黑色素瘤、非小细胞肺癌、淋巴瘤、肝癌等18个癌种；其中，在中国已获批鳞状细胞癌、转移性食管癌、转移性非小细胞肺癌、转移性结直肠癌以及IV期黑色素瘤等10余个适应症，处于Ⅲ期临床试验阶段的适应症达15个。不止于此，K药还在不断布局多项适应症及联合用药。比如：2025年1月，K药联合维恩妥尤单抗用于治疗尿路上皮癌、单药用于一线治疗通过评估肿瘤表达PD-L1（综合阳性评分（CPS）≥1）头颈部鳞状细胞癌2项适应症获NMPA批准上市；2024年12月，K药联合放化疗获得NMPA批准用于治疗国际妇产科联盟（FIGO）2014分期标准下的Ⅲ-ⅣA期宫颈癌患者；此外，K药新剂型——皮下注射剂的研发也在加速推进中，它的到来有望进一步提升患者的用药便利性，为产品销售额创造增量。 03 降糖、减肥双雄：司美格鲁肽的狂飙 2024年，诺和诺德的司美格鲁肽以292.96亿美元的销售额稳居全球畅销药TOP2之位，距榜首的K药仅一步之遥。司美格鲁肽是一款同时获批用于降糖和减肥的GLP-1激动剂，该药自2017年全球首次上市后，随后仅用6年时间，便飙升至全球畅销药TOP2行列，成为榜单中最大的“黑马”。 目前司美格鲁肽共有3款产品获批在售，分别为Ozempic（注射用降糖药）、Rybelsus（口服降糖药）、Wegovy（注射用减肥药），2024年Wegovy同比涨幅达86%，得益于其销售额的突飞猛进，司美格鲁肽的市场体量得到了质的飞跃，也成为诺和诺德业绩增长的重要驱动力。值得注意的是，原研药司美格鲁肽在中国的核心专利——“酰化的GLP-1化合物”将于2026年3月到期，其多款生物类似药也在加快研发的步伐。 目前国内已有20多家企业的司美格鲁肽生物类似药处于获批临床及以上阶段，其中杭州九源基因、丽珠集团、齐鲁制药、联邦制药4家企业已报产在审，正大天晴药业、倍特药业、石药集团等10余家企业已进入Ⅲ期临床。可以预见，司美格鲁肽的市场之争将愈发激烈。 04 抗凝老将：阿哌沙班的坚守 BMS和辉瑞联合开发的艾乐妥（阿哌沙班）凭借206.99亿美元的销售额，继续稳坐2024年全球畅销药榜单的第三把交椅。其中，BMS贡献约133.33亿美元的销售额，辉瑞的销售额约73.66亿美元。艾乐妥最早于2011年在欧盟获批上市，用于预防静脉血栓栓塞，2012年、2013年相继获批进入美国和中国市场。作为上市至今已10余年的抗凝药“老将”，艾乐妥仍能屹立在全球畅销药榜单的前列，这与其出色的疗效和安全性紧密相关。阿哌沙班是一种口服新型凝血因子Xa抑制剂，能有效抑制血栓的形成，且相较传统的抗凝药华法林等，其出血风险更低，安全性更高。 正因产品疗效显著，阿哌沙班吸引了众多药企的争相仿制，数据显示，目前国内已有超40家企业拥有生产批文，正大天晴药业、科伦药业、嘉逸医药、齐鲁制药等41家企业以新分类获批上市、视同过评。与此同时，伴随专利悬崖的到来，叠加集采控价的影响，原研厂商BMS的市场份额遭大幅挤压，其2024上半年在中国公立医疗机构终端市占比已下跌至不足2%。 2024H1中国公立医疗机构终端阿哌沙班片企业格局 05 GLP-1新贵：替尔泊肽的快速成长 作为降糖、减重领域的潜力新星，礼来的穆峰达（替尔泊肽）于2022年5月首次获FDA批准上市，是全球首款GIP/GLP-1双靶点受体激动剂。不到三年时间，该产品便在2024年收获约164.46亿美元的销售佳绩（降糖版替尔泊肽Mounjaro：115.21亿美元（+124%）、减重版替尔泊肽Zepbound：49.25亿美元（+270%）），并跻身全球畅销药TOP4之列，市场潜力不容小觑。2024年12月，礼来公布的随机、开放标签3b期临床试验SURMOUNT-5研究结果显示，在SURMOUNT-5研究的主要终点中，替尔泊肽实现平均减重比例达20.2%，显著优于司美格鲁肽的13.7%，相对体重减轻倍数达到司美格鲁肽的1.47倍，全面超越司美格鲁肽。可见，替尔泊肽凭借更强的减重效果和新适应症的拓展，正在快速成长。GLP-1受体激动剂因具有降糖、减重、心血管获益和治疗代谢相关脂肪性肝炎（MASH）等作用，近年来备受业内关注。在中国三大终端六大市场，该类药物2023年销售规模首度突破90亿元，同比增长50.6%；2024上半年继续以19.43%的增速增长至超50亿元，预计全年销售额将再创新高。近年来中国三大终端六大市场GLP-1受体激动剂销售趋势（单位：万元） 06 “自免”领域打得火热 三大明星重磅齐上榜 2024年畅销药榜单中，3款“自免”领域明星重磅强势登榜，分别为赛诺菲/再生元的达必妥、艾伯维的Skyrizi、强生/田边三菱的喜达诺。达必妥（度普利尤单抗）2024年销售额达141.48亿美元，同比增长23.1%，排在全球畅销药榜单第五位，在“自免”领域首度称王。该产品于2017年获批上市，是FDA批准的首个治疗特应性皮炎的生物制品；随后其又分别获批了哮喘、鼻息肉、食管炎、荨麻疹、慢阻肺等多项适应症，2023在中国三大终端六大市场销售额接近20亿元，同比涨逾47%。Skyrizi（利生奇珠单抗）2024年销售额同比大涨50.9%，以117.18亿美元的销售成绩踏入百亿美元俱乐部和排在全球畅销药第七位。目前Skyrizi已斩获银屑病、克罗恩病、溃疡性结肠炎等适应症，有望成为艾伯维继修美乐后又一“自免”领域的重磅新品。喜达诺（乌司奴单抗）2024年受生物类似药冲击，销售收入有所下降，为103.61亿美元，在全球畅销药榜单排名第九。据悉，乌司奴单抗专利已于2023年9月到期，多款生物类似药开始崭露头角，其中华东医药的乌司奴单抗注射液（赛乐信®）于2024年11月在中国获批上市，用于成人中重度斑块状银屑病，成为国内首款获批的乌司奴单抗生物类似药。此外，石药集团、百奥泰也分别提交了该产品的上市申请，目前均在审评审批阶段。 总体而言，2024年全球畅销药TOP10以生物药为主，其中肿瘤、自免、代谢等领域表现亮眼。随着新技术的突破和新适应症的不断拓展，比如：GLP-1类药物在减肥、MASH和心血管保护方面的应用，未来市场潜力巨大；ADC新药在癌症治疗中不断取得突破，将为患者提供新的治疗选择；基因疗法也为部分罕见病和难治性疾病带来了治愈的希望……当然，药圈中的重磅炸弹也面临着诸多挑战，专利悬崖是一个不可忽视的问题，像艾乐妥、K药等先后在2026年、2028年专利到期，届时将面临仿制药或生物类似药的冲击，市场份额或受到一定影响。此外，医保控费的压力在持续增大，同质化产品的竞争日趋激烈，这都对药企的创新效率提出了更高的要求，药企需不断加大研发投入，推出更具创新性和竞争力的产品，才能更好地立足于多变的市场中。 来源：米内网数据库、上市公司年报等 END 内容沟通：郑瑶（13810174402） 左下角「关注账号」，右下角「在看」，防止失联

Novo Nordisk's dealmaking dispute with KBP Biosciences, AstraZeneca's purchase of FibroGen China and Ono's FDA approval for a rare tumor drug made our news this week. Novo Nordisk alleges Singaporean biotech KBP Biosciences made misleading statements before the two firms inked a licensing deal worth up to $1.3 billion. AstraZeneca is buying out its roxadustat partner FibroGen in China. Ono Pharmaceutical's $2.4 billion Deciphera acquisition has borne fruit. And more.1. Novo Nordisk to sue KBP Biosciences over alleged fraudulent claims on kidney disease drugNovo Nordisk is alleging that KBP Biosciences intentionally withheld negative clinical data before the Danish company bought the latter’s hypertension candidate ocedurenone in a potential $1.3 billion deal in 2023. Novo plans to seek $830 million in damages from the Singaporean biotech, which was founded by Huang Zhenhua in China. The Singapore International Commercial Court has ordered a freeze of the assets of KBP and Huang as Novo prepares to launch arbitration proceedings in New York.2. AstraZeneca pays $160M for FibroGen's China unit, regional rights to roxadustatAfter ditching FibroGen’s chronic kidney disease drug roxadustat in the U.S., AstraZeneca has decided to take full control of the HIF-PH inhibitor in China. The British pharma is paying $160 million to buy FibroGen’s China unit. Last year, AZ recorded $336 million in revenue from the drug, sold as Evrenzo in China, a 22% increase despite generic competition.3. FDA approves Ono's rare tumor drug from $2.4B Deciphera buyoutOno Pharmaceutical’s Deciphera Pharmaceuticals has won FDA approval for Romvimza as a competitor to Daiichi Sankyo’s Turalio in symptomatic tenosynovial giant cell tumor. The Japanese pharma bought the U.S. biotech last year for $2.4 billion to expand its targeted oncology portfolio and boost its U.S. footprint. Compared with Turalio, Romvimza holds a convenience edge and does not come with a black box warning.4. Otsuka breaks up with cancer candidates on strategic groundsOtsuka has nixed several clinical cancer programs for “strategic reasons.” Among the candidates, the only one that the company was developing in the U.S. was OPB-111077, an oral STAT inhibitor that entered the clinic in 2012. The drug was mostly recently tested in a lymphoma trial starting in 2019 until enrollment stopped last year. The other three are being tested only in Japan.5. Siemens Healthineers plans 'mega depots' to bolster US supply chain amid 'geopolitical uncertainties'As President Donald Trump’s new tariffs on China and Mexico are expected to impact medical devices, Siemens Healthineers said it’s building new “mega depots” for spare parts and other inventory in New York City and Oakland, California. The company cited “geopolitical uncertainties” as a potential threat to a stable medtech supply chain.6. Radiance rolls into ROR1 race, paying $15M for ADC rival to Merck’s frontrunnerRadiance Biopharma is paying $15 million upfront for rights to a ROR1-directed antibody-drug conjugate from a subsidiary of China’s CSPC Pharmaceutical. The deal could be worth more than $1 billion if the drug reaches certain sales milestones. After reporting a 100% complete response rate, Merck & Co. has moved its ROR1 ADC into phase 3 testing in diffuse large B-cell lymphoma.Other News of Note: 7. Amid Merck supply squeeze, ImmunityBio and Serum Institute snag FDA blessing for BCG expanded access program8. Ascletis' swift surge into obesity continues with competitive oral GLP-1 data9. FDA hits pair of Indian API makers with warning letters, import alerts

On a recent earnings call, AstraZeneca CEO Pascal Soriot said that, “longer term, we see continuous opportunity for growth in China.” AstraZeneca is paying $160 million for FibroGen’s China business, giving the U.K.-based Big Pharma the regional rights to oral anemia drug roxadustat.The two companies' relationship around roxadustat stretches back over a decade. A year ago, AstraZeneca returned rights to the HIF-PH inhibitor in the U.S. and certain other countries but retained an interest in China and South Korea, where the drug is approved under the brand name Evrenzo.Today’s acquisition sees AstraZeneca pay FibroGen an enterprise value of $85 million along with $75 million of net cash that FibroGen currently holds in China. Once the transaction closes—expected in mid-2025—FibroGen said it will repay its term loan facility to investment funds managed by Morgan Stanley Tactical Value in a move that the biopharma said would “further simplify the company’s capital structure.”FibroGen entered the new year with $121.1 million in cash and equivalents. The sale of the Chinese subsidiary and repayment of the Morgan Stanley loan should together extend FibroGen’s cash runway into 2027, the company said.For AstraZeneca, the prize is the rights to roxadustat in China, where the drug is a category leader for the treatment of anemia in chronic kidney disease. Chinese regulators are also mulling whether to extend the approval to chemotherapy-induced anemia. China approved a generic version of roxadustat made by local pharma giant CSPC Pharmaceutical last summer, and several other companies have filed their copies for approval in the country.  Astellas already owns the rights to roxadustat in certain markets such as Europe, where the drug was approved in 2021. Today's deal means FibroGen retains the rights to roxadustat in its other existing markets like the U.S., where approval hopes were stalled after the FDA rejected an application for chronic kidney disease in 2021 and then the drug failed a phase 3 anemia trial in 2023. When it comes to the U.S., FibroGen said in this morning’s release that it “continues to evaluate a development plan for roxadustat in anemia associated with lower-risk myelodysplastic syndrome, a high-value indication with significant unmet medical need.” The biotech is hoping to meet with the FDA in the second quarter to determine the potential next steps for the development program, the company added.FibroGen CEO Thane Wettig said the sale of the Chinese subsidiary “bolster[s] our company on several fronts.”“It strengthens our financial position, meaningfully extending our cash runway into 2027, and enables us to continue progressing the clinical development program for FG-3246, our first-in-class, CD46 targeting antibody-drug conjugate, and FG-3180, our companion PET imaging agent, in mCRPC,” Wettig added. “After a thorough evaluation of alternatives, we believe selling our China operations and repaying our term loan is in the best interest of FibroGen’s stakeholders.”China is a major market for AstraZeneca, but the Big Pharma has faced challenges in recent months, including a potential fine for millions of dollars of importation taxes as authorities investigate the company’s former China head Leon Wang.In a fourth-quarter earnings call earlier this month, AstraZeneca CEO Pascal Soriot said that, “longer term, we see continuous opportunity for growth in China.”