Lomefloxacin Hydrochloride

Traditional large pharmaceutical companies Hengrui Pharmaceutical and Stone Pharmaceutical Group, which have made remarkable achievements in research and development and business expansion, experienced a significant decline in profitability in the third quarter of 2024 when there was no fault in the innovative drug product line. In the face of competition from biotechnology companies, these two large pharmaceutical companies have achieved the revival of innovation transformation, especially Hengrui Pharmaceutical, which has been approved for the listing of 17 Class A new drugs in China, and ranks among the top three domestic listed drugs in the same target. The 12 innovative pharmacological products approved since 2021 should be in the market growth and climb stage. However, Hengrui Pharmaceutical's revenue in the third quarter of 2024 was 6.589 billion yuan, up 13% year-on-year, down 13% quarter-on-quarter, and the net profit attributable to the parent company was 1.188 billion yuan, up 1.91% year-on-year. If we take into account the capitalization of R&D expenditure of about $126 million, there is actually negative growth. What the hell happened? Hengrui Pharmaceutical's operation and research and development have not made mistakes, and there is no need to reflect. However, even with efforts and efforts, the results are still not satisfactory and there may still be certain problems. The traditional big pharma model of relying on domestic demand may have reached its limits. Although each innovative drug of Hengrui Pharmaceutical ranks among the top three in China, it faces fierce competition from small and medium-sized pharmaceutical companies in each segment, and there is no absolute leading advantage. Although Hengrui has a commercialized portfolio of 17 innovative drugs, its peak sales and life cycle are decisively influenced by the level of payment. Hengrui does not yet have a drug with annual sales of $1 billion, and there is no hope in the short term. Lack of peak sales, the number to gather, essentially did not leave the generic drug stage to win the model of quantity, earn hard money, and eventually may be a dream in ten years, in place. Based on Zbrutinib's sales in 2024, once you have a drug with annual sales of $2 billion, all domestic competitors will no longer matter, and you need to consider a higher level of issues. Geopolitical uncertainty looms, but innovation and internationalization are still the only way for traditional large pharmaceutical companies. Hengrui Pharmaceutical suddenly announced plans to secondary listing in Hong Kong, it seems to have the intention of breaking the game. As of the third quarter of 2024, Hengrui Pharmaceutical is in the New Drug application (NDA) stage or has been listed in the first class of new drugs and second class of new drugs summary. Innovative drugs bear social benefits and public welfare responsibilities in the domestic market. According to Galaxy Securities, according to the sales data of the world's top 25 best-selling drugs in 2021, assuming that the drug price level in the United States is 100%, the average drug price in the United Kingdom, the European Union and Japan is about 20%-25% of the United States, and the price system of innovative drugs in China is relatively low, and the average drug price is 10% of the United States. Innovative drugs benefit from positive externalities in the domestic market, including engineer dividends and clinical resource advantages. Considering the difference in payment environment, the reasonable conversion ratio of pharmacoeconomics in the United States and China may be about 1/7, while the actual rate is as low as 1/10, and the difference between them is the subsidy provided by innovative drugs to the positive externalities of the domestic market. In the 2024 medical insurance negotiations, a total of 162 general-name drugs participated in the negotiation/bidding, including 117 kinds outside the medical insurance list and 45 kinds in the list, with a passing rate of less than 50% in the expert review process, compared with 74.2% in 2022 and 63.8% in 2023. The average decline in new health insurance negotiations over the years: 59% in 2016, 44% in 2017, 57% in 2018, 61% in 2019, 51% in 2020, 62% in 2021, 60% in 2022, and 61.7% in 2023. The 2024 decline is about to be revealed. From a more macro perspective, on November 18, the Ministry of Finance announced the general public budget expenditure for the period from January to October 2024, and the health expenditure was 1,652.1 billion yuan, down 8.5% year-on-year, the largest decline among the 10 major expenditure subjects. Hengrui has not yet shaken off the shadow of centralized purchasing. Since the implementation of the ninth batch of national centralized procurement of products involving carpofungin acetate for injection from March 2024, sales in the first half of 2024 decreased by 279 million yuan compared with the same period last year; Among the products involved in local centralized procurement, the sales of ioformol injection, sevoflurane for inhalation and papaverine hydrochloride injection in the first half of 2024 decreased by 276 million yuan year-on-year. Three major generic drugs with sales of more than 1 billion yuan (Lomefloxacin/Lodisloxacin/Butorphanol) are still facing potential centralized procurement risks. In the third quarter of 2024, the net profit attributable to the parent company was 758 million yuan, down 50% year-on-year and 46% quarter-on-quarter, showing a cliff-like decline. Among the seven business lines, the anti-tumor therapy segment was the most competitive and saw the most severe decline in performance, with revenue in the third quarter and the first nine months down 31.2 percent and 17.6 percent year-on-year, respectively. This is mainly due to the price reduction of the two products, Jinyouli (PEGylated recombinant human granulocyte stimulating factor injection) and Dometic (Doxorubicin hydrochloride liposome injection), by about 58% and 23% respectively in the centralized drug procurement of the Beijing-Tianjin-Hebei "3+N" alliance. Revenue in the cardiovascular treatment field in the third quarter decreased by 26.7% year-on-year, mainly due to the fact that Xuanning (levoamlodipine maleate tablets and disperse tablets) was not selected for the eighth batch of national centralized procurement in 2023, resulting in a greater impact on its sales in hospitals that strictly implement the centralized procurement policy, especially the decline in the second quarter and the third quarter was more significant. In the third quarter, the revenue of the nervous system treatment field decreased by 15.8% year-on-year. The core product of Embip was mainly due to the strict control of the top drugs in the hospital in the environment of strict control of medical costs, resulting in a relatively large decline in sales.

即使是老大哥也遇到商业化瓶颈了。 传统Big pharma恒瑞医药、石药集团在研发、BD都取得重要进展，创新药产品集群未出现断档的情况下，2024Q3盈利能力却断然下滑。 两家大型药企面对Biotech冲击，创新转型都实现中兴之局，特别是恒瑞累计在国内获批上市17款1类新药，并且在同靶点新药中，均实现国产前三上市，其中，2021年以来获批上市的12款创新药应该处于放量爬坡期。 然而，恒瑞2024Q3营收65.89亿元，同比增长13%，环比下降13%，归母净利润11.88亿元，同比增长1.91%，考虑到约1.26亿元研发开支资本化，其实是负增长。 到底发生了什么？恒瑞经营、研发没有出现失误，无需反思。可是，如果你努力了，尽力了，结果仍然是悲伤的，可能还是哪里有问题。 传统Big pharma立足内需的发展模式可能已到极限。虽然恒瑞每款创新药都是国内前三，但在每个细分方向上面临着中小药企的贴身肉搏，不存在断层式领先。虽然恒瑞拥有17款创新药的商业化组合，但其销售峰值、生命周期受到支付水平的决定性影响。 恒瑞至今没有10亿美元分子，短期也看不到希望。峰值不够，数量来凑，本质上并没有脱离以量取胜的仿制药发展阶段，挣的是辛苦钱，卷到最后，有可能十年一梦原地踏步。 参考泽布替尼2024年销售额，当你手握一个20亿美元分子时，国内所有竞争对手都不再重要了，需要考虑的是更高层面的问题。 地缘关系阴云密布，但创新前置+国际化仍是传统Big Pharma的必由之路。恒瑞突然传出赴港股二次上市，似有破局之心。 恒瑞医药处于NDA或已上市阶段的一类新药和二类新药汇总 截至2024Q3 01  稳不住了 创新药在国内市场承担社会效益、公益责任。据银河证券，按照2021年全球前25名畅销药品的销售数据，假设美国药价水平为100%，英国、欧盟和日本的平均药价约为美国20%-25%，而我国创新药价格体系定价水平处于相对较低位置，平均药价为美国10%。 创新药受益于国内市场的正外部性，包括工程师红利、临床资源优势。考虑到支付环境差异，美中药物经济学合理换算比例可能约为1/7，而实际低至1/10，其间的差价即为创新药对国内市场正外部性给出的补贴。 2024年医保谈判，共有162个通用名药品参加谈判/竞价，包括医保目录外117种和目录内45种，在专家审评环节通过率不足50%，而2022年为74.2%，2023年为63.8%。 历年新增品种医保谈判平均降幅：2016年59%，2017年44%，2018年57%，2019年61%，2020年51%，2021年62%，2022年60%，2023年61.7%。2024年是多少？即将揭晓。 站在更宏大的视角，11月18日，财政部公布2024年1-10月一般公共预算支出情况，卫生健康支出16521亿元，同比下降8.5%，在10项主要支出科目中降幅最大。 恒瑞没有走出集采的阴影。2024 年3 月开始执行的第九批国家集采涉及产品注射用醋酸卡泊芬净，2024H1销售额同比减少 2.79 亿元；地方集采涉及的产品中，碘佛醇注射液、吸入用七氟烷及盐酸罂粟碱注射液2024H1销售额同比减少2.76亿元。销售额超过10亿元的仿制药三大单品（洛美沙星/洛迪沙星/布托啡诺）仍面临潜在的集采风险。 石药集团也稳不住了。 2024Q3，归母净利润7.58亿元，同比下降50%，环比下降46%，断崖式后撤。7条业务线中，抗肿瘤治疗领域内卷最严重、业绩下滑最大，Q3和前9月收入分別同比下降31.2%和17.6%，主要由于津优力（聚乙二醇化重组人粒细胞刺激因子注射液）及多美素（盐酸多柔比星脂质体注射液）两款产品的价格于京津冀“3+N”联盟药品集中采购中分别下调约58%和23%。心血管治疗领域Q3收入同比下降26.7%，主要由于玄宁（马来酸左氨氯地平片及分散片）落选2023年国家第八批集采，使其在严格执行集采政策的医院的销售受到较大冲击，尤其本年第二季度及第三季度的跌幅较为显著。神经系统治疗领域Q3收入同比下降15.8%，核心产品恩必普主要因医院在严格控制医疗费用的环境下，对在医院用量排名靠前的药品实施较严格管控，使销售有较大幅度的下跌。 大单品不宜出风头。 恒瑞医药已获批药物在同靶点新药中，均为国产前三款上市   国海证券统计，截至2023H1 02 国产前三 据National Science Foundation数据，2017年我国在产品试验开发阶段投入金额占比84%，显著高于美国、日本、韩国63-67%水平，而基础科研6%、应用科研11%，低于美国、日本、韩国14-17%、20-22%水平。基础科研、应用科研薄弱，但从生产能力维度分析，Fast-Follow是一种实用主义策略，更有利于后发追赶。 在一个领域做到前三是优秀，在每个领域都做到前三是卓越，恒瑞把Fast-Follow策略做到极致。 自免 夫那奇珠单抗今年8月获批上市，为首个国产白介素抗体（IL-17A），填补国产银屑病生物制剂领域空白。诺华司库奇尤单抗（IL-17A）2024年前三季度全球销售额45.45亿美元。 在研JAK1小分子艾玛昔替尼具备全新的结构母核，以中重度特应性皮炎适应症为代表，效果与已上市JAK1选择性抑制剂相当，且已有中重度特应性皮炎、强直性脊柱炎、类风湿性关节炎、成人重度斑秃4项适应症提交国内NDA，溃疡性结肠炎、银屑病关节炎适应症处于III期临床阶段，国内进度领先。 SHR-1703（IL-5）国产进度仅次于三生国健，针对EGPA（嗜酸性肉芽肿性多血管炎）适应症处于III期临床。在长效IL-5抗体研发赛道中，SHR-1703临床进度位于国内第一，具有BIC潜力，半衰期超3个月，可延长给药周期、降低用药频次。 SHR4640是痛风领域进度最快的国产URAT1抑制剂，处于III期临床阶段。我国高尿酸血症总体患病率为13.3%，患病群体数达1.77亿人；痛风总体发病率为1.1%，每年新发患病人数约1466万，存量痛风患者人数超过8000万人。国内临床常用痛风药物以非布司他院内端销售占比居首，但安全性存在争议，其作为国内最新一款痛风药是2013年在国内获批，10年未有痛风新药获批，从安全性改善和疗效提升来看，痛风用药市场存在较大未满足的临床需求。研究表明约90%的痛风是由于尿酸排泄减少，而其中URAT1转运蛋白负责肾脏约90%的重吸收，为调节尿酸水平的主要转运蛋白。 ADC SHR-A1811（HER2 ADC）国产进度仅次于科伦博泰，今年9月上市申请获得受理，共有6项适应症被CDE纳入突破性治疗品种名单。据Cancer Research数据，SHR-A1811在第一三共DS8201的基础上payload-Dxd酰胺的α位引入一个手性环丙基，从而展现出较好的稳定性，安全性有提升。鉴于SHR-A1811的成功，相同的linker、payload结构被普遍用于公司HER3、CLDN18.2 ADC设计上。 SHR-A1904（CLDN-18.2 ADC）在同赛道进度全球第三，仅次于信达生物、礼新生物。参考公司专利，在自研h1902-5、h1901-11单抗上加上SHR-A1811、SHR-A2009相同的linker和payload片段，即依托现有平台，实现快速研发。 双抗 SHR-1701（PD-L1/TGF-β）有望成为全球首个用于HER2阴性G/GEJA一线治疗的双抗，今年9月上市申请获得受理，目前全球尚无TGFβ单靶点、PD-L1/TGFβ双靶点药物上市。 GLP-1 HRS9531（GLP-1/GIP）在国产GLP-1双靶点减重药中，进度仅次于信达生物玛仕度肽，III期临床试验于2024年中期完成患者入组，预计在52周随访后于2025年8月获得数据读出和NDA。 小核酸 HRS-5635是用于慢性乙型肝炎治疗的一款小干扰RNA(siRNA)疗法类新药，2024H1进入II期临床试验阶段，在乙肝功能性治愈小核酸药物领域，恒瑞在上市公司中领跑。 恒瑞医药已上市8款自研化学小分子，与同靶点更早上市产品的药物结构差异较小  资料来源：Chemicalbook、丁香园、国海证券研究所 03  挣脱笼子 这是一场壮观的行军，恒瑞在每个队列都走在最前面。 但问题在于，恒瑞始终在国内市场这个笼子里，头上容易顶到天花板，身后则是甩不掉的追兵。 细分领域中小龙头还存在舒适区，随着核心产品陆续获批上市放量，业绩和市值仍有向上拓展空间。因为国内市场容量的限制，传统Big pharma腾挪的空间已比较局促。恒瑞未公布单个产品的销售额，我们可以把所有创新药看成一个商业化组合。 这个组合需要抵消仿制药销售额的下滑，新入组合的增量品种也需要抵消老化品种销售额的下滑，如果不能避免2024Q3营收环比停滞的情况再现，那么近看是遥遥领先，远看却是在泥潭中挣扎。 最可怕的是对手变得更强。 恒瑞不仅面临传统Big pharma中生、石药、齐鲁的竞争，Bio pharma信达生物的追赶，还在每个细分领域面临中小龙头的围殴。在生物科技寒冬期，这些中小龙头戒掉浮躁之气，降本增效，注重均衡发展，甚至兼备管线临床价值和商业化能力。连快断奶的一级市场Biotech也不好惹，批量输出BIC、FIC新药管线，据医药魔方统计，2019-2023年整体License-out供给端主力为Biotech，占比均在50%以上，2023年占比为69%，其中一级市场早期公司在国内出海License-out中占比大幅提升，2023年已达到54%。 唯有一计可破局，当你拥有一个或一批10亿美元分子时，将立即从内需市场中超脱出来，远离控费与内耗，远有武田制药，近有百济神州，可为参照。 恒瑞BD和国际化能力均有长足进步，但突破点不在PD-1和GLP-1。 恒瑞近日重新向美国FDA提交卡瑞利珠单抗联合甲磺酸阿帕替尼用于不可切除或转移性肝细胞癌患者一线治疗的BLA，并得到正式受理，审评日期为2025年3月23日。卡瑞利珠单抗2018年被Incyte退货，原因被认为是微小血管瘤副作用，即使闯关FDA成功，也来得太晚了，海外PD-1市场也只剩残羹冷炙。 恒瑞GLP-1产品组合出海，以一己之力带火NewCo模式，但国产GLP-1药物BD首付款普遍较低，因为相比海外大厂只是进度落后的同质化产品。除非是下一代GLP-1药物，在增肌、增加能量消耗、停药不反弹的痛点上有所突破。 失落和阵痛是暂时的，希望在未来，恒瑞已具备批量产生BIC或FIC管线的能力，加上BD和国际化能力的匹配，也将拥有自己的10亿美元分子，诞生下一个武田制药。 声明：发表/转载本文仅仅是出于传播信息的需要，并不意味着代表本公众号观点或证实其内容的真实性。据此内容作出的任何判断，后果自负。若有侵权，告知必删！ 长按关注本公众号  粉丝群/投稿/授权/广告等 请联系公众号助手 觉得本文好看，请点这里↓