更新于：2024-05-01
Bevacizumab-awwb
贝伐珠单抗生物类似药（安进）
更新于：2024-05-01
概要
基本信息
原研机构 |
非在研机构- |
最高研发阶段批准上市 |
最高研发阶段(中国)终止 |
特殊审评- |
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序列信息
Sequence Code 1167865647H
来源: *****
Sequence Code 1167865648L
来源: *****
关联
7
项与 贝伐珠单抗生物类似药（安进） 相关的临床试验A Phase2 study to investigate the efficacy and safety of Atezolizumab and bevacizumab with live bacterial product for unresectable HCC
开始日期2023-08-25 |
申办/合作机构- |
A Phase I/II Study of AMG 510 in Combination With MVASI in Patients With Advanced, Unresectable or Metastatic KRAS G12C Mutant NSCLC With Asymptomatic Brain Metastasis.
This is a multicenter, non-randomized, open-label, phase I/II study to evaluate the safety and tolerability of AMG 510 plus MVASI in subjects with advanced KRAS p.G12C mutant non-small cell lung cancer (NSCLC) with small, untreated brain metastases.
开始日期2022-06-15 |
申办/合作机构  CRITERIUM, Inc. [+1] |
A Randomized, Double-blind, Phase 3 Bridging Study Evaluating the Safety and Efficacy of ABP 215 Compared With Bevacizumab in Chinese Subjects With Advanced Non-Squamous Non-Small Cell Lung Cancer
The purpose of this research study is to assess the efficacy and safety of ABP 215 compared to Bevacizumab in Chinese patients with advanced non-small cell lung cancer (NSCLC).
开始日期2021-05-15 |
申办/合作机构  Amgen, Inc. [+1] |
100 项与 贝伐珠单抗生物类似药（安进） 相关的临床结果
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100 项与 贝伐珠单抗生物类似药（安进） 相关的转化医学
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100 项与 贝伐珠单抗生物类似药（安进） 相关的专利（医药）
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19
项与 贝伐珠单抗生物类似药（安进） 相关的文献（医药）2023-10-28·Clinical colorectal cancer
Real-World Safety and Effectiveness of a Bevacizumab Biosimilar (ABP 215) in Metastatic Colorectal Cancer Patients in Canada.
Article
作者: Winson Y Cheung ; Setareh Samimi ; Kim Ma ; Gregory John Knight ; Shaqil Kassam ; Bruce Colwell ; Annie Beaudoin ; Mark David Vincent ; Mateya Trinkaus ; Alain Filion ; Katerine Marquis ; Hatim Karachiwala ; Timothy Asmis ; Lucas Sideris ; Rajvi J Wani ; Elaine Ngan ; Naila Inam ; Yinhao Du ; Leyla Nunez ; Maria Eberg ; Mistre Alemayehu ; Pierre-Francois Meyer ; Johanna Mancini ; Carlye Cirone Morris
BACKGROUND:
ABP 215 is a biosimilar to the reference product, bevacizumab, and was one of the first biosimilars approved by Health Canada for the first-line treatment of metastatic colorectal cancer (mCRC). This study aimed to address gaps in real-world evidence (RWE) including patient characteristics, treatment safety (primary objective), and effectiveness (secondary objective) for first-line ABP 215 therapy in Canadian patients with mCRC.
MATERIALS AND METHODS:
Retrospective data were collected in 2 waves, at least 1 year (Wave 1) or 2 years (Wave 2) after commercial availability of ABP 215 at each participating site.
RESULTS:
A total of 75 patients from Wave 1 and 164 patients from Wave 2 treated with a minimum of 1 cycle of ABP 215 were included. At least one safety event of interest (EOI) was recorded for 34.7% of Wave 1 and 42.7% of Wave 2 patients. The median progression free survival (PFS) for Wave 1 and 2 patients were 9.47 (95% confidence interval [CI]: 6.71, 11.90) and 21.38 (95% CI: 15.82, not estimable) months, respectively. Median overall survival was not estimable for Wave 1 and was 26.45 months for Wave 2.
CONCLUSION:
The safety and effectiveness of ABP 215 observed in this real-world study were comparable to clinical trial findings and to other RWE with longer PFS in the current study.
2023-09-25·BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy
Real-World Clinical Outcomes of Bevacizumab-awwb Biosimilar versus Bevacizumab Reference Product in Patients with Metastatic Colorectal Cancer.
Article
作者: Catherine Pham ; Fang Niu ; Thomas Delate ; Gary L Buchschacher ; Yan Li ; Ekim Ekinci ; Kim Le ; Rita L Hui
BACKGROUND:
Bevacizumab-awwb was the first biosimilar approved for cancer treatment in the USA. Limited information is available on the real-world comparative safety and effectiveness of bevacizumab biosimilars, especially for indications granted approval through extrapolation.
OBJECTIVE:
To evaluate the real-world outcomes of patients with metastatic colorectal cancer (mCRC) initiated on bevacizumab-awwb versus bevacizumab reference product.
PATIENTS AND METHODS:
This was an observational, longitudinal cohort study of US adult patients with mCRC from four integrated care delivery systems who were newly initiated on bevacizumab-awwb between 1 July 2019 and 30 March 2020 or bevacizumab reference product between 1 July 2015 and 30 June 2018. Patients were followed until 1 year after treatment initiation, end of plan membership, or death, whichever occurred first. The primary outcome of overall survival (OS) was analyzed using a binary non-inferiority test with lower margin of 10% and adjusted Cox proportional hazards regression analysis to assess all-cause mortality if non-inferiority was met. Secondary outcomes included counts of doses received, treatment duration, all-cause hospitalizations, and incidence of serious adverse events.
RESULTS:
A total of 1445 patients initiated on either bevacizumab-awwb (n = 239) or bevacizumab reference product (n = 1206) were included in the analysis. The mean overall age was 60 ± 13 years, 46% of patients were female, and 51% were white. The OS rate was 72.8% and 73.1% for patients receiving bevacizumab-awwb and bevacizumab reference product, respectively (p < 0.01 for non-inferiority). The adjusted hazard ratio for mortality was 1.01 (0.77-1.33, p = 0.93). There were no statistically significant differences in secondary outcomes between the study groups.
CONCLUSIONS:
These findings suggest that bevacizumab-awwb is as effective and safe as bevacizumab reference product for the real-world treatment of mCRC.
2023-01-01·Therapeutic advances in medical oncology
Real-world outcomes among patients with metastatic colorectal cancer treated first line with a bevacizumab biosimilar (bevacizumab-awwb).
Article
作者: Ran Jin ; Adesuwa S Ogbomo ; Neil A Accortt ; Lincy S Lal ; Geetanjali Bishi ; Darcie Sandschafer ; Jerome H Goldschmidt
Background:
Bevacizumab-awwb (MVASI®) was the first U.S. Food and Drug Administration-approved biosimilar to Avastin® (reference product [RP]) for the treatment of several different types of cancers, including metastatic colorectal cancer (mCRC), an indication approved based on extrapolation.
Objectives:
Evaluate treatment outcomes in mCRC patients who received first-line (1L) bevacizumab-awwb at treatment initiation or as continuing bevacizumab therapy (switched from RP).
Design:
A retrospective chart review study.
Methods:
Adult patients who had a confirmed diagnosis of mCRC (initial presentation of CRC on or after 01 January 2018) and initiated 1L bevacizumab-awwb between 19 July 2019 and 30 April 2020 were identified from the ConcertAI Oncology Dataset. A chart review was conducted to evaluate patient baseline clinical characteristics and effectiveness and tolerability outcomes during the follow-up. Study measures were reported stratified by prior use of RP: (1) naïve patients and (2) switchers (patients who switched to bevacizumab-awwb from RP without advancing the line of therapy).
Results:
At the end of study period, naïve patients (n = 129) had a median 1L progression-free survival (PFS) of 8.6 months [95% confidence interval (CI), 7.6-9.9] and a 12-month overall survival (OS) probability of 71.4% (95% CI, 61.0-79.5%). Switchers (n = 105) had a median 1L PFS of 14.1 months (95% CI, 12.1-15.8) and a 12-month OS probability of 87.6% (95% CI, 79.1-92.8%). During treatment with bevacizumab-awwb, 20 events of interest (EOIs) were reported in 18 naïve patients (14.0%) and 4 EOIs reported in 4 switchers (3.8%), of which the most commonly reported events were thromboembolic and hemorrhagic events. Most EOIs resulted in emergency department visit and/or treatment hold/discontinuation/switch. None of the EOIs resulted in death.
Conclusion:
In this real-world cohort of mCRC patients who were treated 1L with a bevacizumab biosimilar (bevacizumab-awwb), the clinical effectiveness and tolerability data were as expected and consistent with previously published findings from real-world studies of bevacizumab RP in mCRC patients.
30
项与 贝伐珠单抗生物类似药（安进） 相关的新闻（医药）2024-03-10
·医药魔方
鸟鸣山跃石不转，寒日不见清风盼。乍暖还寒、最难将息的早春二月在渐行渐远的光阴流转间悄然而至，落日余晖映照下的一城山色半城湖在晚霞的交织下略显孤寂，比之往昔少了些喧嚣、添了抹静谧。春意未浓、冬雪犹在、几分凋零、些许黯然。浮生观澜，恍如一梦，愿诗与远方均不再遥远，乘风归去来兮，繁花片片落满地。整体概况2023年全球生物药市场规模达到了5600亿美元，占到了全球医药整体市场的39%，预计将在五年后的2028年突破8000亿美元，进一步将份额提升至40%以上。近年来以欧美为首的的全球生物类似药市场规模不断扩大，对于生物类似药的当下和未来，多家研究机构就发展速度和规模给出了自己的预测，虽然数字不尽相同，但均异曲同工的肯定了持续稳定发展的大趋势，未来增速相比此前的预计有所放缓。不同机构的全球生物类似药市场规模与增速预测2023年全球销售额TOP100药品中，以单抗为代表的生物大分子药物数量达到了一半。除去疫苗产品外，2023年全球销售额TOP20生物产品均为单抗和抗体融合蛋白。入围门槛进一步提高，各产品全球销售额均在37亿美元以上，其中一半的产品全球收入在50亿美元以上，5个产品突破了百亿大关，K药十年磨一剑接力Humira登顶药王宝座。销售额增幅最大的瑞莎珠单抗Skyrizi和度伐利尤单抗Imfinzi增长均超过了50%，走下神坛的阿达木单抗Humira降幅达到了32%。美国市场处于绝对核心地位，TOP20中95%的产品美国市场收入在全球销售额中的占比在50%以上。产品主要分布在抗肿瘤和自体免疫领域，除奥瑞珠单抗和瑞莎珠单抗外的其他18个产品均已登陆中国市场。75%的产品在2010年及之后获批，其中获批时间最早的依那西普距今已有25年，凭借美国市场潜水艇专利对生物类似药的限制依然年年上榜，获批最晚的瑞莎珠单抗距今不到5年。2023年全球销售额TOP20生物药原研产品（非疫苗类）2023年美国医药市场整体规模再创新高、突破了7000亿美元，以48%的占比继续领跑全球，蓬勃发展的生物药品在整体销售额中的占比达到了51%，IQVIA预计将在2032年达到5800亿美元的规模，份额占比增长至56%。2023年美国市场生物类似药销售收入在上年增速已经放缓的基础之上出现了小幅下滑，最终交出了72.5亿美元的答卷，究其原因一方面在于半数以上的之前已获批产品在竞争日渐加剧的大背景下的价格持续下滑部分抵消了生物类似药不断渗透带来的增量正效应，另一方面部分产品的市场经过几年的洗牌在销量规模上已经日趋平衡，增幅比较有限，同时以曲妥珠单抗为代表的个别分子在其他同类创新药不断涌现下出现了连续萎缩，加之以阿达木单抗领衔的新上市产品的表现低于预期，对整体销售额的带动相对比较有限，各因素叠加共同造成了连续增长之后的首次下滑。过去的一年里，经历了漫长等待的阿达木单抗生物类似药集体上市，革命尚未成功的背后依然可以感受到那股虽千万人吾往矣的不屈力量；那他珠单抗、托珠单抗和乌司奴单抗三个分子的首个生物类似药顺利获批，带动获批分子总数量增加至14个；非格司亭和贝伐珠单抗两个分子的生物类似药份额逼近85%，不断刷新着象征着生物类似药荣光的崭新纪录；乌司奴单抗等一系列新产品顺利实现与原研的和解，开启了提前上市的加速模式。前路依然漫长，但这充满暖意的一幕幕还是给这个难忘的寒冬带来了无尽的希望。获批&上市2023年共有5个生物类似药产品获批，产品共涉及阿达木单抗等5个分子以及Celltrion等5家公司，其中那他珠单抗、托珠单抗和乌司奴单抗均为首个生物类似药获批。Amgen的Wezlana在获批的同时被授予可互换资格，成为史上第7个以及2023年第3个获此殊荣的生物类似药；Celltrion和Sandoz均以累计5个的生物类似药产品获批数量上升至并列第三位；百奥泰自研的托珠单抗和贝伐珠单抗生物类似药相继获批，实现了中国力量在美国生物类似药领域的历史性突破。2023年美国生物类似药获批一览从获批位次看，Celltrion的Yuflyma成为第9个获批的阿达木单抗生物类似药，Avzivi成为第5个获批的贝伐珠单抗生物类似药，Tyruko、Tofidence和Wezlana三个产品均为各自所属分子获批的首个生物类似药产品。从审评时长看，百奥泰的Avzivi和Celltrion的Yuflyma分别达到了1104天和910天，打破了贝伐珠单抗和阿达木单抗两大分子此前全部生物类似药在一个审评周期内获批的记录，Yuflyma由于原液生产场地的现场检查问题经历了两次CR回复后才最终获批；Tyruko由于涉及REMS的方案变更被认定为重大变更，导致审评时间延期3个月后获批；Tofidence和Wezlana两个产品均在一个审评周期内获批。截至目前，聚乙二醇化非格司亭生物类似药以738天的平均审评时长位列榜首，平均审评时长分布在500-550天的依那西普、曲妥珠单抗和贝伐珠单抗生物类似药紧随其后，雷珠单抗、甘精胰岛素以及新获批的托珠单抗和乌司奴单抗四个分子的生物类似药目前保持着一个审评周期获批的最短审评时长。由Amneal在售的非格司亭生物类似药Releuko依旧以1693天保持着单品最长审评时间的历史记录，Sandoz的聚乙二醇化非格司亭生物类似药Ziextenzo和Pfizer的阿法依伯汀生物类似药Retacrit分别以1530天和1246天的审评时长位居历史第二和第三位。从上市情况看，2023年共有13个生物类似药上市，打破了2019年7个新产品上市的历史记录，其中阿达木单抗生物类似药上市数量达到了9个，聚乙二醇化非格司亭共有Avsola和Fylnetra两个产品上市，甘精胰岛素和贝伐珠单抗各有1个生物类似药产品上市。所有上市产品中仅有Yuflyma一个2023年新获批产品，从获批到上市仅历时40天，其余产品自获批后均经历了不同时间的等待，阿达木单抗生物类似药的平均等待时长为1216天，其中时间间隔最久的阿达木单抗首仿产品Amjevita达到了2321天。2023年美国生物类似药上市一览从申报数量看，2023财年共有19个生物类似药BLA首次向FDA申报，打破了2017财年14个生物类似药BLA申报的历史记录，随着后续以地舒单抗为代表的新一代生物类似药进入集中申报期，这一记录仍有望在短期内被持续刷新。截至目前，将今年2月刚刚获批的阿达木单抗生物类似药Simlandi囊括在内，美国以351（K）途径申报的生物类似药获批总数量和上市数量已经分别达到了46个和38个。从产品类型看，共涉及维持治疗、抗肿瘤、自体免疫、胰岛素和眼科五大领域的14个分子，其中数量最多的阿达木单抗共有10个生物类似药获批，其中9个已经上市，成为当下竞争最为激烈的产品，数量最少的阿法依泊汀只有1个生物类似药获批并上市。从公司看，共涉及包括了原研创新型、专注研发型以及大型仿制药公司在内的14家公司，其中Pfizer以8个产品获批和7个产品上市的双第一战绩独占鳌头。曲妥珠单抗等7个分子实现了全部获批生物类似药均已上市，获批未上市的8个生物类似药有5个受限于专利，其余则主要因为商业化策略暂未上市或放弃上市。渗透&价格美国市场生物类似药在过去的2023年里进一步加速渗透，2022年在售的9个分子的生物类似药整体份额在2023年均取得了不同程度的增长，但增速已经明显放缓，回扣和报销制度中存在的固有顽疾依然制约着生物类似药发展的速度和可持续性，特别是在非抗肿瘤产品领域中表现的愈发突出，重磅产品阿达木单抗生物类似药去年的集体上市与万众期待的宏伟目标相差甚远，低价本身在生物类似药领域竞争中的决定作用与小分子化药相比存在着天壤之比，很难做到一低定乾坤。流通渠道中PBM等核心参与方在目录制定等重要环节的开放程度相对比较有限，无法在充分公平竞争的条件下将所有生物类似药囊括其中，医生在开具处方环节中很多时候受限于报销体系本身以及出于安全性风险的考虑偏重求稳的态度对开具生物类似药的积极性并不高，流通环节中的参与方处于各自利益的考虑无法形成合力，制度本身的变革和教育推广的力度等多个方面的努力仍然需要在未来不断加深，生物类似药的发展之路在经历了冲破初期阻碍实现破冰之后的全面突围仍需时日。前路漫漫，但生物类似药在美国医药支出节省方面取得的持续性成绩依然值得欣喜，根据AAM报道，2022年涉及八大分子的全部生物类似药节省医药支出达到了94亿美元，历史累计节省支出达到了236美元。美国生物类似药历年节省医药费用一览美国各分子生物类似药平均价格及原研品历年价格变化一览从具体数字看，拥有生物类似药在市销售三年以上的7个分子的生物类似药2023年整体销量份额均在40%以上，其中贝伐珠单抗和非格司亭两个分子的生物类似药的占比已经逼近85%，进一步刷新着历史最高份额记录；10个有生物类似药在售的分子中，有7个在市生物类似药数量的企业在3家及以上，阿达木单抗生物类似药在售单品数量达到了9个，打破了去年曲妥珠单抗5家竞争的最大数量记录。2022年新上市的雷珠单抗生物类似药在去年将整体份额提升了26%，成为了2023年渗透幅度增长最大的产品；聚乙二醇化非格司亭和阿法依伯汀两个分子的原研产品通过采用跟进生物类似药同步降价的策略最大程度上限制了生物类似药竞争对手的上量，两个分子生物类似药的2023年整体销量份额被限制在42%，增幅均未超过1%，成为了2023年渗透最慢的产品。从具体单品份额看，美国首个生物类似药Zarxio以58%的份额排名榜首，贝伐珠单抗和阿法依伯汀两个分子的首仿产品Mvasi和Retacrit以46%和42%的份额紧随其后；2023年新上市的阿达木单抗生物类似药整体销量份额不足2%，表现大大低于预期；10个分子份额排名榜首的10个生物类似药中，有8个为首仿产品，雷珠单抗的首仿产品Byooviz和利妥昔单抗的首仿产品Truxima成为唯二没有借助最早上市的优势登顶各自生物类似药份额榜首的产品；阿达木单抗的首仿产品Amjevita以1.4%的份额排名全部首仿产品末尾。2018-2023美国市场在市销售各分子生物类似药销量份额变化一览严冬大背景下的降价潮在过去的一年里愈发激烈，多个产品相比上年的ASP价格降幅超过了50%，降幅较大的产品主要集中在各分子目前市场份额较高的生物类似药中，其中曲妥珠单抗首仿产品Kanjiti的降幅达到了77%，成为了过去一年里降幅最大的单品；与当前个分子原研产品相比，曲妥珠单抗和利妥昔单抗两个分子的当前最低生物类似药ASP价格（平均销售价格）已经跌破20%，阿法依泊汀和雷珠单抗两个低竞争产品的比率保持在85%以上；7个分子当前最低生物类似药产品ASP价格相比于生物类似药上市之前的原研品价格降幅在35%-95%之间，6个产品的降幅超过了75%，排除掉去年刚有生物类似药上市的阿达木单抗，当前拥有在市生物类似药产品数量最多的聚乙二醇化非格司亭的价格降幅最大，达到了94%，2022年上市的雷珠单抗产品降幅最小，仅有35%。从原研自身价格变化来看，生物类似药上市之前ASP价格平均增幅最大的聚乙二醇化非格司亭原研产品Neulasta在生物类似药进入后不断疯狂跟进，以63%的降幅蝉联原研品降价冠军，雷珠单抗原研产品Lucentis以21%的降幅紧随其后，其余原研产品降幅均未超过10%，其中贝伐珠单抗原研产品Avastin和阿法依泊汀原研产品Epogen/Procrit价格为正增长；目前已经稳定占据近60%市场份额的非格司亭首仿产品Zaxio成为了生物类似药中屈指可数的在过去一年涨价的产品，增幅达到了11%。总体来看，对于具体生物类似药单品而言，进入市场的位次和之后的总体竞争程度共同决定了其发展的高度， 在流通渠道各环节中首先被覆盖从而占据一席之地基础上的低价策略才是有意义的。比之小分子产品，个体生物类似药在起点落后的情况下依靠后天逆天改命的难度要大很多，如果再遇上个像Amgen一样对自己更狠的原研，逆袭几乎没有可能。美国生物类似药涉产品价格变化一览策略&管线生物类似药的围城之殇在过去的一年里依然在延续，总体来看针对美国市场的生物类似药研发热度依然保持在较高的水平上，FDA 2023年公布的生物类似药研发计划中包括的生物类似药项目依然保持在100个以上，涉及的分子突破了50个。面临着生物类似药市场的新形势，在自身利益最大化的目标下，各家公司在结合实际情况明确了调整策略的基础上在过去的2023年里进一步付诸于目标引领下具体操作的执行。随着阿达木单抗生物类似药Abrilada在2023年的上市，Pfizer在美国市场的生物类似药在售数量达到了7个，继续在获批和上市数量上双榜领跑的同时也宣告了其美国市场生物类似药的商业化前工作的收关。受限于Comirnaty和Paxlovid两大新冠产品收入的下滑，Pfizer的2023年全球销售额相比上年大降41%，公布的5个美国市场生物类似药销售额（11.2亿美元）相比上年也下滑了26%，寄望于通过收购Seagen布局ADC领域产品等措施力挽狂澜，最新公布的研发管线中项目数量达到了112个，其中已不见生物类似药的踪影，近60%涉及新分子实体产品，无法一剑定乾坤的生物类似药之于急于扭转颓势的宇宙大药厂终究只是匆匆过客。Biocon于去年9月正式完成了Viatris美国市场生物类似药业务的交接和整合工作，人员数量增加到150人以上，打通了此前在以欧美为代表的法规市场所不具备的药政、供应链和商业化环节，具备了生物类似药从研发到销售的垂直一体化实力，实现了从幕后走上台前的角色转变。Biocon与Viatris前身之一的Mylan于2009年起以单抗产品起步开始合作生物类似药产品，随后在2013年进一步将合作拓展到胰岛素产品领域，双方合作在美实现了曲妥珠单抗、聚乙二醇化非格司亭和甘精胰岛素三个分子的生物类似药的首家获批（后两者同时为首家上市），目前聚乙二醇化非格司亭生物类似药Fulphila和甘精胰岛素生物类似药Semglee分别以16%和12%的份额排名各自分子的生物类似药份额首位。此次交易的总金额达到了33.35亿美元，双方各取所需，Viatris剥离掉生物类似药以后也向着全球瘦身计划的完成更进一步。Biocon包括已获批产品在内的全球生物类似药管线产品总数量达到了20个（包括了8个未披露名称的早期项目），针对美国市场的门冬胰岛素和贝伐珠单抗等四个产品已经处于FDA审评过程中，随着2022年马来西亚场地FDA审计问题的解决，2024年有望迎来新产品的获批，后续的地舒单抗等三个新项目已经处于III期临床中。完成交接后的Biocon在美国市场生物类似药策略上也开始从此前的自研自产逐步向自研与外部引进相结合的混合业务模式开始转变。Sandoz于去年10月正式从诺华剥离，向着成为小分子仿制药和生物类似药全球领导者的目标独立前行，虽然在五年的过渡期内仍将以签订服务协议的形式由Novartis提供生物类似药研发和生产的相关资源，但Sandoz在分拆之前已经开始着手通过投资自建生产和研发设施并展开了一系列相关外部合作进行补强。首先在去年3月决定投资4亿美元在斯洛文尼亚伦达瓦兴建一处厂房设施用于生物类似药的生产，预计可于2026年投产，随后在5月与Just-Evotec Biologics达成合作，依靠其研发和生产平台丰富Sandoz自身的生物类似药产品管线及生产设施建设，将管线产品数量提升至24个，7月宣布将在斯洛文尼亚卢布尔雅那进一步投资9000万美元用于其生物类似药技术研发中心的建设，11月在德国霍尔茨基兴启动了一处投资2500万欧元的新的生物类似药研发中心，一系列组合拳的打出为其日后独立进行生物类似药的研发和生产打下了坚实的基础。在合作方面，Sandoz在此前与Polpharma、EirGenix、Bio-Thera和Gan&Lee等多家外部公司进行合作的基础上于去年9月与Samsung Bioepis就乌司奴单抗生物类似药达成合作，随后又在今年1月宣布以1.7亿美元的首付款将Coherus的雷珠单抗生物类似药Cimerli收入麾下，在阿柏西普即将申报的基础上进一步补强了自己的眼科产品管线。已公布的Sandoz 2023年全球生物类似药销售额达到了15.92亿美元（+10%），预计全年将突破20亿美元，目前其在美国市场共有三个产品在售，其中非格司亭生物类似药Zarxio作为美国市场首个生物类似药产品不断延续着上市以来的良好表现，当前销量份额已接近60%；聚乙二醇化非格司亭注射液生物类似药Ziextenzo在去年下半年出现了较大的销量下滑，丢掉了去年生物类似药的榜首位置，2023年新上市的阿达木单抗生物类似药Hyrimoz同时被Express Scripts、Optum/United和CVS Caremark三大PBM目录所覆盖，在激烈的竞争中占据了有利的位置，另外两个获批的依那西普生物类似药Erelzi和那他珠单抗生物类似药Tyruko限于专利暂未上市，后者有望于今年上半年冒险上市；其与百奥泰合作的贝伐珠单抗生物类似药Avzivi以于去年12月获批，预计最快将于今年实现上市。在研产品管线中，地舒单抗等6个产品已经处于FDA审评阶段，有望于今年获批，阿柏西普预计将于今年完成申报。Teva的生物类似药策略比较明晰，力争在以外部合作为主导结合少量自研的开发模式下将产品管线数量提升至20个，目前Teva研发费用的20%用于生物类似药，计划在未来三年中逐步将这一比例降至接近10%，从而将更多的投入用于创新药的研发，将目前40%的投入比例提升至60%-80%。Teva当前处于审评和在研阶段生物类似药产品共有16个，其中7个为自研，另外9个来自于合作伙伴Alvotech，双方于2020年建立了针对美国市场的生物类似药合作联盟，合作产品从最初的5个逐步扩展至如今的9个，遗憾的是双方合作的乌司奴单抗和阿达木单抗两个已申报生物类似药产品在产品本身没有问题的情况下受限于Alvotech位于雷克雅未克场地的FDA检查缺陷问题未能如期获批，本来有望首个获批高浓度规格并授予可互换资格的阿达木单抗生物类似药因此也错失了去年生物类似药集中进入市场的时机。Teva的全球销售额在经历了自2018年开始的连续5年下滑后终于在2023年以158亿美元（+10%）的战绩实现了正增长，其中包括与Celltrion合作的曲妥珠单抗Herzuma和利妥昔单抗Truxima两个生物类似药在内的美国仿制药产品模块总收入为34.75亿美元（-2%），前者以不足2%的市场份额位列五家曲妥珠单抗生物类似药的末尾，后者以30%的份额位列三家利妥昔单抗生物类似药的第二位。目前除了两个处于FDA审评阶段的生物类似药以外，自研的奥马珠单抗以及与Alvotech合作的阿柏西普和格列木单抗三个产品处于III期临床阶段，自研的地舒单抗已经顺利完成了III期临床试验，未来Teva将在目前与Alvotech合作的基础上进一步寻求其他外部伙伴的合作。在完成了美国小分子化药市场自售的试水后，作为美国生物类似药市场先驱之一的Celltrion生物类似药的销售体系于去年顺利搭建完成并于4月份上市了首个自售产品贝伐珠单抗生物类似药Vegzelma，随后又在7月初上市了阿达木单抗生物类似药Yuflyma（2024年1月进一步上市了80mg/0.8ml的高浓度规格产品），加上目前由Pfizer销售的英夫利昔单抗生物类似药Inflectra以及由Teva销售的利妥昔单抗生物类似药Truxima和曲妥珠单抗生物类似药Herzuma，Celltrion已经实现了全部已获批的5个生物类似药产品的上市，在数量上仅次于排名首位的Pfizer，其中英夫利昔单抗的皮下注射版本生物类似药已于去年10月获批，将由Celltrion以ZYMFENTRA的商品名自售，Pfizer将继续销售静脉注射版本产品。与Biocon一样，Celltrion在具备了商业化销售能力后也实现了研产报销一条龙，不同之处在于Biocon的销售团队主要来自于此前Viatris的已有原班人马，Celltrion的销售团队经历了新建的过程，在Amgen、Pfizer和Coherus工作过的Thomas Nusbickel 于今年2月初被任命为Celltrion美国子公司的CCO负责生物类似药的商业化相关工作。Celltrion目前共有地舒单抗、乌司奴单抗、阿柏西普以及托珠单抗四个产品处于FDA审评过程中，奥马珠单抗已经完成III期临床试验，奥瑞珠单抗单抗处于III期临床试验中。Samsung Biologics在将与Biogen的合资公司Samsung Bioepis变为自家独有后又被传出将进一步收购Biogen的生物类似药业务，双方的合作始于2012年Samsung Bioepis的建立，目前Biogen在退出合资公司后依然将负责Samsung Bioepis当前在美国市场在售的雷珠单抗注射液生物类似药Byooviz以及未来新产品阿柏西普的商业化工作。Samsung Bioepis去年在此前与Organon和Biogen在美国市场进行生物类似药合作的基础上增加了Sandoz这一新的合作伙伴，目前其在美国市场共有5个生物类似药产品获批，除去因专利无法上市的依那西普外，与Organon合作的英夫利昔单抗、曲妥珠单抗以及阿达木单抗三个产品生物类似药连同和Biogen合作的雷珠单抗注射液生物类似药Byooviz均已上市，销售情况并不尽如人意，四个产品的2023年份额均未超过10%。目前管线中的贝伐珠单抗、乌司奴单抗和阿柏西普三个生物类似药产品已经处于FDA审评阶段，地舒单抗和依库珠单抗两个生物类似药产品已经完成了III期临床试验，帕博利珠单抗的生物类似药的I期临床试验也已经于今年1月份正式启动。随着未来战略重心将集中在肿瘤产品领域，Coherus于今年1月份将非核心产品雷珠单抗生物类似药Cimerli的美国市场权益转让给Sandoz，去年上市的阿达木单抗生物类似药同样被界定为非核心产品，另一个目前在售的聚乙二醇化非格司亭生物类似药Udenyca是其当下最为重要的核心生物类似药产品，随着Udenyca自动注射器版本产品在去年年底的增补获批，有望在近年带动该产品整体销量的增长其未来产品管线将更多的集中在创新药领域。作为生物类似药界的另类存在，Amgen在过去的一年里依然延续着自己的双面人生，作为地舒单抗等多个分子的原研产品和阿达木单抗等多个分子的首仿产品与对手们上演着一出出攻防大战。目前Amgen在美获批生物类似药数量已经达到了6个，仅次于Pfizer的7个，除去年刚刚获批的乌司奴单抗限于专利暂未上市（和解日期为2025年1月）外，其余5个产品均已上市，其中年报中公布的Mvasi和Kanjiti两个生物类似药产品的美国市场销售额分别为5.11亿美元（-15%）和1.09亿美元（-59%），去年首仿上市的阿达木单抗生物类似药产品Amjevita取得了1.26亿美元的收入。目前生物类似药研发管线中的依库珠单抗和阿柏西普生物类似药处于FDA审评中，已披露的临床阶段的产品仅剩了纳武利尤单抗。Amneal在去年成功完成了聚乙二醇化非格司亭生物类似药Fylnetra的上市，将美国市场在售生物类似药产品数量增加至3个，目前均面临多个竞争对手的局面，在均为最晚入市的情况下当前份额均比较惨淡，在研管线中新增加了与mAbxience合作的地舒单抗，目前处于III期临床试验阶段。Fresenius的聚乙二醇化非格司亭生物类似药Stimufend和阿达木单抗生物类似药Idacio均在去年上市，目前在研管线中的妥珠单抗、利妥昔单抗和乌司奴单抗三个生物类似药产品均已处于FDA审评阶段，地舒单抗生物类似药也已经完成了III期临床试验；Hikma的地舒单抗和乌司奴单抗两个生物类似药产品均已完成III期临床试验，管线中暂时没有披露的新产品加入；Lupin处于FDA审评中的聚乙二醇化非格司亭生物类似药仍未获批，雷珠单抗已经完成了III期临床试验。中国军团中百奥泰的贝伐珠单抗和托珠单抗两个生物类似药产品已经获批，复宏汉霖的曲妥珠单抗生物类似药、甘李的甘精、门冬、赖脯三大胰岛素生物类似药均已处于FDA审评阶段，健友与通化东宝也在去年9月达成了合作协议，双方将在未来针对美国市场开发前述三大胰岛素的生物类似药产品。总体来看，上述各家公司的在审产品中包含了多个美国市场已有生物类似药上市的老分子产品，这些产品申报时间相对较早但限于自身问题尚未获批，例如于2019年申报的Samsung Bioepis的贝伐珠单抗生物类似药和2021年申报的Lupin的聚乙二醇化非格司亭生物类似药；近几年内即将有生物类似药登陆市场的重磅分子产品已有多家申报，例如已有Amgen、Samsung Bioepis、Celltrion和Biocon申报的阿柏西普以及Celltrion和Sandoz已经申报的地舒单抗；处于III期临床中的产品除了阿柏西普、地舒单抗以及乌司奴单抗三大重磅产品的生物类似药外，也包括了奥马珠单抗、戈利木单抗和帕妥珠单抗等竞争相对缓和的生物类似药产品。从重叠度来看，地舒单抗一枝独秀，几乎出现了在了全部上述主要公司的产品清单上，该产品的2023年全球销售额达到了66亿美元，预计未来将出现与阿达木单抗相似的十家以上竞争的白热化场面，Amgen目前仍在针对该产品积极防御。针对后续第四波重磅产品的生物类似药研发进展也逐渐浮出水面，以新晋药王帕博利珠单抗为例，Samsung Bioepis已于今年1月启动了I期临床试验，Sandoz在2月同步启动了I期和III期临床试验，其他诸如Alvotech、Formycon和Xbrane等美国生物类似药研发常客的该产品生物类似药也即将进入临床阶段，原研的皮下注射版本也在研发过程中以抵御未来生物类似药的竞争，未来临床、审评的速度以及各家不同的专利诉讼情况将共同决定新药王首仿产品的归属。诉讼进展决定生物类似药上市位次的BPCIA诉讼大战在2023年迎来了第11个年头，在经历了前面几年的缓和期后，随着生物类似药BLA申报数量再创新高，2023年的诉讼案件数量回升到了7起，截至2023年底，美国历史累计BPCIA诉讼数量已经突破了60起，其中包括了一些双方针对同一产品在不同地区或针对不同专利发起的同源性诉讼。美国历年BPCIA诉讼数量过去的2023年里共有三起诉讼落下帷幕，均已和解告终，其中两起于2022年发起、一起于2023年发起，共涉及曲妥珠单抗、乌司奴单抗和托珠单抗三个分子，其中两个产品已经获批待上市，平均和解时间为173天，其中托珠单抗仅历时103天；2023年之前的诉讼仍有两起尚未了结，分别涉及阿柏西普和那他珠单抗；2023年发起的七起诉讼中共有四起针对阿柏西普一个分子，另外三起分别涉及地舒单抗、托珠单抗和利妥昔单抗，其中地舒单抗和托珠单抗两个分子为首次涉及BPCIA诉讼。七起诉讼的原告方共涉及Amgen、Genentech和Regeneron三家公司，被诉方涉及Sandoz等六家公司，诉讼涉及的专利数量平均为32个，其中涉及阿柏西普的四起诉讼涉及专利数量均超过了30个。从范围上看，2013年-2023年间在负责初审的地区法院层级总共由Amgen、Genetech、Janssen、Abbvie、Biogen和Regeneron六家原研药公司针对目前有生物类似药获批的阿达木单抗等12个分子以及阿柏西普等目前尚未有生物类似药获批的3个新分子向Celltrion等近20家集团公司提起诉讼，共涉及40余个生物类似药（部分未获批）。从时间看，2017（11起）和2018（12起）两年成为诉讼发起最为集中的时间段，占据了全部诉讼数量的近40%，2013年仅有一起诉讼提出。从公司表现看，Genentech以提出18起诉讼的数量排名原告第一，同时分饰原告和被告两角的Amgen以承接9起诉讼的战绩排名被告第一，Celltrion和Sandoz以各被诉8起的数量并列排名被告第二。从耗时看，Sandoz的非格司亭生物类似药Zarxio和Celltrion的英夫利昔单抗生物类似药Inflectra从最初被诉到最终胜诉均历时近五年，成为拉锯时间最长的生物类似药产品，Sandoz的阿达木单抗生物类似药Hyrimoz从被诉到最终与原研和解仅历时2个月，成为诉讼耗时最短的产品；从结果看绝大多数诉讼均以和解告终。在专利诉讼之外的第二战场，2023年美国各公司针对阿柏西普等多个产品共发起了23件IPR多方复审和2件PGR授权后复审，从历史数据来看产品看，曲妥珠单抗原研产品Herceptin、利妥昔单抗原研产品Rituxan和阿达木单抗原研产品Humira成为累计IPR数量最多的产品，针对阿柏西普的IPR数量已经超过了10件，大有追赶前述老产品之势；从被无效专利类型看，应用专利被挑战次数以绝对优势领先其他类型专利。产品表现1.阿达木单抗（Adalimumab）原研产品/公司：Humira/Abbvie 美国获批时间：2002/12 竞争难度：★★★★★十年磨一剑，10在历史发展的长河中的确是一个很有意思的数字，从初出茅庐到登顶王座，Humira用了十年，在连续蝉联十年后迎来了另一个历时十年终成正果的新王霸主Ketruda，随着以Amgen为首的9个阿达木单抗生物类似药在2023年的陆续登场，在巅峰末期连续两年完成200亿神迹的Humira正式走下神坛，两代药王之间十年的传承在2023年圆满收官。Humira历年全球销售额一览2023年，Humira在美国市场受到初步冲击的形势下最终交出了144亿美元的答卷，相比上年出现了32%的下滑，美国市场收入在全球总收入中的占比下降至84%，依然是Abbvie最为依赖的Humira全球最大市场。在去年Humira销量突破1100万支的基础上，2023年包括9家生物类似药在内的美国市场总销量实现了3%的小幅增长，98%的市场份额依然掌控在原研Humira的手中；从包装形式看，注射笔产品的份额略有提升突破了90%；从规格看，100mg/ml高浓度产品的份额达到了85%，40mg/0.4ml的主流规格占据了其中份额的94%。随着Teva和Alvotech联手开发的Simlandi在2月底的获批，目前美国市场阿达木单抗生物类似药获批总数量已经达到了创纪录的10个，除了Simlandi刚刚获批尚未上市，其余9个产品均在2023年登陆了市场，在Amgen的Amjevita作为首仿于去年1月底率先亮相后，Sandoz等7家公司在7月初同步上市了各自的生物类似药产品，Pfizer在10月份最晚入场。八仙过海，各显神通，其中BI的Cyltezo等3个产品被授予了自动互换资格，Sandoz的Hyrimoz等5个产品拥有体验度更好的高浓度产品，在价格方面，Amgen等5家公司推出了高低两种价格方案，Pfizer等4家公司只提供了一种WAC方案，高价高回扣、低价低回扣，虽然实际ASP价格暂不知晓，但最高折扣达到86%的WAC价格已经反映了生物类似药上市后激烈的市场竞争。各家陆陆续续与渠道中的PBM、药房等机构达成了合作协议，其中Celltrion 于去年10月与PBM公司Ventegra达成了合作，Sandoz的Hyrimoz同时被Express Scripts、Optum/United和CVS Caremark等多个PBM的目录所覆盖，Cigna则在去年9月将Amgen的Amjevita移出目录后选择了首个被FDA授予可互换资格的BI产品Cyltezo。总体来看，阿达木单抗生物类似药的2023年市场整体份额仅有2%，全面的渗透仍然需要一定的时间，可喜的是多家PBM已经进行了策略的调整，逐渐向多家生物类似药敞开了大门，市场竞争随着Teva的即将入局将愈发激烈，2024年将成为生物类似药迎来转折的关键一年。2.贝伐珠单抗 (Bevacizumab)原研产品/公司：Avastin/Roche 美国获批时间：2004/02 竞争难度：★★★★☆2023年贝伐珠单抗原研产品Avastin在欧美两大市场的下滑速度相比最近几年有所缓和，最终全球收入以15.73亿瑞士法郎（约合17.5亿美元）惨淡收关，整体降幅达到了26%（以恒定汇率计为19%），持续刷新着历史新低。Avastin历年全球销售额一览2023年，原研产品Avastin美国市场销售收入为4.84亿瑞士法郎（约合5.38亿美元），相比上年下滑了19%，美国市场在全球收入中的区域占比继续维持在30%左右。美国市场贝伐珠单抗的2023年整体销量达到了242万支（+7%），其中生物类似药占比进一步增长至历史最高的84%。Amgen的贝伐珠单抗首仿生物类似药Mvasi以46%的全年平均份额占据销量榜首位置，但销售额受限于激烈竞争造成的价格下滑已下降至5.11亿美元（-15%）；Pfizer的二仿产品Zirabev以36%的销量份额继续稳第二把交椅，销售额下滑至3.04亿美元（-26%）。Amneal和Celltrion分别于2022年和2023年上市的生物类似药Alymsys和Vegzelma份额均未超过3%。从规格看，100mg/4ml产品的销量份额升至53%，略占优势；整体市场价格进一步大幅下滑，当前最低平均销售价格（来自Zirabev）已降至16美元/10mg（-50%），相当于原研品价格的23%，原研产品Avastin的价格小幅提升至70美元/10mg（+5%）。Sandoz和百奥泰合作的Avzivi 已于去年年底获批，成为美国第五个获批的贝伐珠单抗生物类似药，截至目前暂未上市，Avzivi获批的初始效期只有12个月，在已有四家在市销售且初始获批效期（Mvasi：36个月，Zirabev：40个月，Alymsys：30个月，Vegzelma：两个规格分别为24/48个月）均比之更久的情况下处于不利的局面。Biocon的BMAB-100 (2020年3月接受审评)、Centus的FKB238（2019年11月接受审评）以及Samsung Bioepis的SB8 (2019年11月接受审评)三个贝伐珠单抗生物类似药历时多年仍处于FDA审评阶段，未来该产品的美国市场竞争将会进一步加剧。3.曲妥珠单抗 (Trastuzumab)原研产品/公司：Herceptin/Roche 美国获批时间：1998/09 竞争难度：★★★★★前有生物类似药追兵，后有同领域创新药来敌的Herceptin在过去的一年交出了16.26亿瑞士法郎（约合18.1亿美元）的答卷，全球销售额整体降幅达到了24%，（以恒定汇率计为16%），迎来了2017年全球销售峰值过后的六连跌。Herceptin历年全球销售额一览2023年，原研产品Herceptin美国市场销售继续下滑至3.31亿瑞士法郎（约合3.7亿美元），26%的降幅与上年基本持平，美国市场在全球收入中的占比降至历史最低的20%。2023年的美国曲妥珠单抗生物类似药之争依然延续着五强争霸的格局，全年生物类似药市场整体销量份额进一步提升至71%。2023年该产品的整体美国市场销量继续下滑至106万支（-8%），420mg大规格产品份额以接近一半。2023年首仿产品Amgen的Kanjinti表现保持平稳，以32%的份额领跑各路生物类似药，美国市场1.09亿美元的销售额相比上年大幅下滑了58%；Pfizer的三仿产品Trazimera以23%份的销量份额排名生物类似药第二，Pfizer年报中报道的净销售额出现了800万美元的负值，其余三个在市生物类似药的份额均未超过10%；当前最低平均销售价格（来自Kanjinti）大幅降至7.38美元/10mg（-77%），仅为原研品价格的9.7%，原研产品Herceptin的价格小幅下降至76美元/10mg（-3%）。截至目前，Sandoz与Eirgenix合作的EGI014 (2021年12月申报 )、Tanvex的TX-05(2021年10月接受审评) 、Prestige的HD201以及复宏汉霖与Accord合作的HLX02（2023年2月接受审评）四个曲妥珠单抗生物类似药产品均已处于FDA审评过程中，未来美国市场该产品生物类似药数量预计将达到10家以上，竞争进一步白热化。4.利妥昔单抗（Rituximab）原研产品/公司：Rituxan/Roche 美国获批时间：1997/11 竞争难度：★★★☆☆Roche抗肿瘤三件套同频共振，其中历史最为悠久的利妥昔单抗原研产品Mabthera/Rituxan ( 分别用于欧洲和美国市场)在2023年紧随Avastin和Herceptin的步伐同步下滑，全球销售额降至16.3亿瑞士法郎（约合18.1亿美元），降幅达到了21%（以恒定汇率计为15%）。Mabthera/Rituxan历年全球销售额一览2023年，原研产品Rituxan美国市场销售收入为9.87亿瑞士法郎（约合11亿美元），相比2022年下滑了25%，占到了原研产品全球销售额的61%；利妥昔单抗生物类似药的整体销量占比进一步增加至77%， 2023年该产品的整体美国市场销量为213万支（+2%），相比上年略有提升，约55%的份额来自于100mg/10ml的小规格产品。作为比首仿晚两个月上市的二仿产品，Pfizer的Ruxience以40%的全年份额继续领跑，3.08亿的美国市场销售额相比上年下降了24%，Teva的首仿产品Truxima以10个百分点的劣势位居第二，于2021年最晚上市的Amgen的Riabni份额仅为6%；当前最低平均销售价格（来自Ruxience）已降至14.5美元/10mg（-53%），相当于原研品价格的19%，原研产品Rituxan的价格小幅下降至75美元/10mg（-3%）。除当前在市销售的3家外，后续针对美国市场的竞品相对比较匮乏，目前处于FDA审评中的生物类似药仅剩Dr Reddy’s和Fresenius合作的产品，该产品已于2023年7月被FDA接受审评，最快有望于今年获批，短期内该产品的竞争将维持在原研产品以及3-4个生物类似药之间。 5.非格司亭（Filgrastim）原研产品/公司：Neupogen/Amgen 美国获批时间：1991/02 竞争难度：★★★☆☆2023年，随着销售额的一降再降，Amgen的非格司亭原研品Neupogen已经在年报中被归入单品销售额较小而不再单独报告的其他产品，与该分类中另外三个生物类似药（英夫利昔单抗生物类似药Avsola，利妥昔单抗生物类似药Riabni以及依库珠单抗生物类似药Bekemv一起取得了3.31亿美元的全球销售额，预计Neupogen全球销售额将在近两年内跌破一亿美元，成为美国市场已有生物类似药上市的分子原研产品中表现最为惨淡的那个。Neupogen历年全球销售额一览2023年，该产品的美国整体市场量约230万支，与去年基本持平，其中预冲注射器产品占比突破了85%；从市场竞争来看，除去Teva以351(a)途径获批的Granix外，过去一年依然延续着Sandoz、Pfizer和Amneal三家仿制药竞争的局面。生物类似药的整体销量份额进一步小幅提升至85%，非格司亭成为目前美国市场生物类似药渗透率最高的分子，其中Sandoz的首仿产品Zarxio以近60%的份额稳居榜首，Pfizer的二仿产品Nivestym的份额已提升至23%，2022年最晚上市的Releuko排名末尾，份额仅为1%。从价格看，原研产品Neupogen的价格相较于仿制药上市前几乎没有大的变化，当前最低平均销售价格（来自Nivestym）已降至0.217美元/1mcg（-36%），相当于原研品价格的23%，Zarxio成为了为数不多的实现价格增长的生物类似药，相比上年价格提升了11%，Neupogen价格基本与去年持平。除去去年刚有生物类似药上市的阿达木单抗外，非格司亭在美国市场所有已有生物类似药上市的分子中销售额排名垫底。截至目前，Tanvex于2020年11月重新申报的BLA仍处于审评中，目前看后续已暂无其他以美国市场为目标的处于晚期的在研非格司亭生物类似药。6.聚乙二醇化非格司亭（PEG-filgrastim/PEG-GCSF）原研产品/公司：Neulasta/Amgen 美国获批时间：2002/01 竞争难度：★★★★★在美国市场激烈竞争造成价格大跌的背景下，选择不断跟进与生物类似药硬扛价格争取以价保量的原研产品Neulasta在2023年的全球销售额跌破10亿美元，最终以8.48亿美元（-26%）抱憾收关。随着Fresenius和Amneal两家生物类似药产品在2023年的相继上市以及Coherus Onbody自动注射器产品在今年2月份的刚刚登陆，八成以上全球收入来自于美国市场的Neulasta未来之路将更加举步维艰。Neulasta历年全球销售额一览2023年Neulasta美国市场销售额降至7.1亿美元（-26%），在全球销售额中的占比下滑至84%。市场总量约为134万支（+3%），去年只有原研品一家在售的自动注射器产品份额已经降至45%，Coherus于去年上市的独有注射笔产品的份额不足1%，占据另外55%份额的预充注射器产品之争在原研公司Amgen与Coherus等6家生物类似药公司之间展开，Sandoz的三仿产品Ziextenzo在2022年通过大幅降价策略将预充注射器产品份额迅速提升至28%，但在去年下半年出现了销量的大幅下滑，最终以12%份全年总份额将尚未坐稳的榜首位置交出，Viatris/biocon的首仿产品Fulfila增长迅速，再过去一年实现了12%的销量份额提升，最终以29%的份额登顶预充注射器产品份额第一，Coherus的Udenyca在经历了2022年的大幅下滑后相对平稳的将过去一年的份额保持在25%，原研产品Neulasta份额小幅提升至24%，Pfizer的五仿产品Nyvepria以10%的份额排在原有老产品的末尾，Fresenius和Amneal新上市的Stimufend和Fylnetra份额均为超过1%。将预充注射器、注射笔和自动注射器三种形式产品的销量合并计算，在原研保持价格跟进策略的影响下，2023年该产品生物类似药的整体份额与上年基本持平，稳定保持在42%。当前最低平均销售价格（来自Ziextenzo）已降至283美元/支（-72%），相当于原研品价格的49%，Nyvepria价格降至714美元/支（-57%），Neulasta价格跟进至574美元/支（-63%），相比生物类似药进入市场前的价格降幅达到了94%，成为了生物类似药上市后降价幅度最大的原研产品，其余4个生物类似药的平均销售价格均保持在1400美元/支以上。Coeherus在去年5月推出了独有的注射笔产品UDENYCA® Autoinjector，其自动注射器产品UDENYCA® ONBODY™ 在去年10月快速完成收到CRL后的再申报后于去年12月获批，并于今年2月在美国正式上市，成为了首个与原研Neulsata Onpro直接竞争的生物类似药产品，注射时间仅为5分钟，Amgen最后的防御体系将在2024年开始遭遇猛烈冲击，Coherus在未来竞争中的优势愈发明显。Lupin的该产品生物类似药目前处于FDA审评中，目前审评时间已近3年仍未获批。 7.英夫利昔单抗（Infliximab）原研产品/公司：Remicade/J&J 美国获批时间：1998/08 竞争难度：★★★☆☆随着美国等全球多个市场生物类似药渗透的不断加强， 2023年Remicade的销量和价格持续同步下滑，全球销售额降至23亿美元（-21%）。Remicade历年全球销售额一览2023年，Remicade美国市场销售额为12.9亿美元（-20%），在全球销售额中占比继续保持在56%，英夫利昔单抗美国整体市场销售量增加到了995万支（+4%），在原研产品的封锁进一步解开的背景下，生物类似药在商业流通渠道中进入报销目录的比例不断提升，整体份额在2022年大幅提升14%的基础上进一步增加至48%，原研依然占据着半壁江山。目前共有Pfizer的Inflectra、Organon的Renflexis以及Amgen的Avsola三家生物类似药在售，其中早在2016年便已上市的首仿产品Inflectra在过去一年中将份额稳定保持在28%，受降价影响，销售额下降至2.57亿美元（-11%），Renflexis和Avsola的销量份额占比均不足10%。生物类似药于2016年进入市场后带动了整体市场价格的持续下滑，当前生物类似药最低平均销售价格相比首仿上市时原研价格已经下降了85%，当前生物类似药的最低平均销售价格（来自Inflectra）为11.86美元/10mg（-49%），相当于原研品价格的39%，原研产品Remicade的价格小浮下降至30.3美元/10mg（-8%）。Celltrion在2022年底以351(a)途径申报的皮下注射版英夫利昔单抗产品Zymfentra于去年10月用时一轮正式获得FDA批准，初始获批效期达到了39个月，将与目前由合作伙伴的Pfizer代售的首仿产品Inflectra形成双拳出击的合力，完满的诠释了极致研发的魅力。Zymfentra的上市批产品已于2月底空运发往美国，预计将于3月中旬在美上市，定价上将高于目前在售的生物类似药。目前暂时已无其他进展较快的潜在竞争对手在短期内寻求在美申报英夫利昔单抗生物类似药。8.阿法依伯汀/依泊汀α（Epoetin Alfa）原研产品/公司：Epogen &Procrit /Amgen 美国获批时间：1989/06 竞争难度：★★☆☆☆安进负责的阿法依伯汀美国市场部分2023年销售额进一步大幅下滑至2.26亿美元(-55%)，J&J负责的美国及全球其他市场部分因销售额过低自2022年起已不在财报中单独列出，根据此前该产品的整体销售趋势推测其2023年全球整体销售额预计在5亿美元左右。Epogen/Procrit历年全球销售额一览自Pfizer的生物类似药Retacrit于2018年底上市以来，一直未有新的生物类似药获批，2023年该产品的美国市场整体销量下滑至782万支，Retacrit的全年市场份额继续保持在42%，美国市场收入下滑至2.59亿美元（-17%），占到了其全球销售额的76%。当前最低平均销售价格（来自Retacrit）已降至0.72美元/100units（-6%），相当于原研品价格的85%。暂时没有更多关于后续有计划在美国市场开发该产品生物类似药的其他公司的相关进展报道，考虑到该产品整体市场的不断萎缩，预计未来很难有新的生物类似药产品寻求进入美国市场，两个原研品与一个生物类似药竞争的局面仍将继续维持下去。9.甘精胰岛素（Insulin Glargine）原研产品/公司：Lantus /Sanofi 美国获批时间：2000/04 竞争难度：★★★☆☆在包括美国在内的多国政府通过多种举措降低胰岛素产品垄断和药价的努力下加之生物类似药产品的不断渗透， 2023年甘精胰岛素原研产品Lantus的全球销售额已降至14.2亿欧元（折合15.2亿美元），下滑幅度达到了创纪录的37%，迎来了自2016年以来的8连跌。Lantus历年全球销售额一览2023年，Lantus美国市场大幅崩盘，销售额以63%的降幅下滑至2.81亿欧元（折合3亿美元），在全球销售额中占比由34%降至20%，美国市场甘精胰岛素注射液整体销量稳定保持在1.1亿支，Eli Lilly的生物类似药产品Rezvoglar获批15个月后于去年4月正式上市，当前竞争在Eli Lilly、Biocon和原研Sanofi三家之间展开。Sanofi共有原研产品Lantus、升级产品Toujeo以及于2022年推出的非品牌版本三种甘精胰岛素产品，Toujeo成分与Lantus相同但释放活性成分更平缓，低血糖发生率显著降低，但临床的不可替代性相对较低，Biocon于去年正式接手Viatris开始销售具有可互换资格的生物类似药Semglee以及其非品牌版本产品，Eli Lilly在之前销售的以化药NDA获批并完成BLA转换的Basaglar基础上于去年上市了同样具有可互换资格的生物类似药Rezvoglar，目前已经拥有两款甘精胰岛素产品在市销售。2023年，生物类似药的份额进一步提升至13%但增速依然相对缓慢，受《通胀削减法案》的影响，各家在去年均进行了不同程度的降价以响应将患者每月的胰岛素自付费用限制在35美元的要求，从当前的WAC价格看，Lantus和Semglee非品牌版本产品的价格已经分别降至34美元/1000IU和30美元/1000IU，不断刷新着历史最低价格，实际净价将在此基础上进一步降低。美国市场甘精胰岛素各产品当前WAC价格一览Sandoz和甘李合作的甘精胰岛素生物类似药已经于去年2月被FDA接受审评，最快有望于今年获批；Lannett和东阳光合作的甘精胰岛素生物类似药目前也已处于FDA审评过程中；健友与通化东宝于去年9月达成战略合作，共同推进甘精、门冬、赖脯三种胰岛素注射液在美国市场的开发和生产。10.雷珠单抗（Ranibizumab）原研产品/公司：Lucentis /Roche & Novartis美国获批时间：2000/04 竞争难度：★★★☆☆近两年来多个雷珠单抗生物类似药在欧美两大法规市场相继获批和上市，除了以Samsung/Biogen为代表的三大联盟外，作为中国仿制药国际化领军企业的齐鲁制药也在今年初迎来了其雷珠单抗生物类似药Rimmyrah在欧盟和英国的相继获批，实现了国产眼科生物药品出海零的突破。原研产品Lucentis在同领域其他创新药竞品及生物类似药的激烈竞争下不断萎缩，2023年的全球销售额最终以33%的历史最大跌幅定格在19.7亿美元，负责美国市场销售的Roche和美国外其他市场销售的Novartis分别贡献了其中的25%和75%。Lucentis历年全球销售额一览2023年Lucentis美国市场销售额为4.6亿瑞士法郎（折合5亿美元），降幅达到了历史最高的53% ，市场总量下降至94万支(-13%)，预充注射器装产品的份额在目前只有瓶装产品的生物类似药竞争下从2022年的99%下滑至74%。Samsung Bioepis的雷珠单抗首仿产品Byooviz以及Coherus的二仿产品Cimerli于2022年6月和10月相继上市后在2023年里进一步渗透，将生物类似药的整体份额提升至26%，其中Cimerli的份额达到了21%。当前最低平均销售价格（来自Byooviz）已降至173.35美元/0.1mg（-22%），相当于当前原研品Lucentis价格的98%，当前Lucentis最新的平均销售价格为176.94美元/0.1mg（-21%），相比生物类似药上市之前的自身价格已经下降了33%。出于战略层面考虑，Coherus在今年1月将视为非核心资产的Cimerli以1.7亿美元的首付款转让给了Sandoz，未来将更加专注于肿瘤领域的创新药产品，Sandoz借此在阿柏西普的基础上补强了自身的眼科生物类似药产品线；由三大联盟之一的Xbrane/Stada研发的生物类似药产品的再申报已于去年6月被FDA接受审评，预计最快于今年4月获批，此前与Bausch + Lomb在美国市场签订的商业化合作协议已经终止；Lupin的LUBT010已经顺利完成了针对美国市场的III期临床试验。未来展望光阴似箭，美国市场生物类似药在2005年初露头角后在纷繁变化的大环境中走到了第十个年头，在摸索中突破，在逆境中前行，政策、流通和竞争等多个环节在接下来互有你我的博弈中形成的合力将共同指引着生物类似药未来之路的方向和轨迹。在研发方面，尽管以Viatris为代表的部分公司基于自身策略逐步开始退出了生物类似药领域，但针对美国市场的生物类似药整体研发依然在如火如荼的进行着，在严冬的大背景下各家的研发策略更加务实，对于项目的选择和把控愈发谨慎，稳中求进、以进促稳的基调深入贯穿其中。随着全球范围内生物药的蓬勃发展，大分子的研发已不再向多年之前那样高不可攀，通过相关配套资源的自建补强或兼并引入，各家在生物类似药研发领域的差距也在逐步缩小。在研发涉及产品类别逐步拓展和丰富的变化下，肿瘤和自身免疫两大领域依然是各路诸侯最为关注的焦点区域，针对中短期有上市机会的重磅单品的研发大战其火爆程度大有追赶小分子之势。在生物类似药早期入局者实力差距红利逐步淡化的趋势下，动辄十家以上竞争对手针对部分大药进行竞争的格局将成为不再陌生的新常态。思路的清晰与否决定了能不能选得对、做得早，研发的实力强弱决定了能不能走得快、筑得牢，在此基础上临床的策略优劣进一步决定了能不能入的快、报的早，质量的水平高低决定了能不能查的少、批的早，专利的破局深浅则决定了能不能谈的好、上的早，以研发为引擎的全面布局和综合硬实力共同决定了能否先人一步、胜人一筹。在合作方面，速度、成本和风险的联合驱动使得带给各色玩家更多选择与可能的外部联姻在数量上逐步增多，在类型上也更加丰富。在生物类似药市场开放初期，以Mylan/Biocon和Samsung/Biogen为代表的早期联盟更多的针对一揽子早期产品展开合作并在此基础上逐步拓展，随着近年来行业内各类参与方整体实力的不断提高，合作可选的对象更加广泛，在研发和生产资源逐步供大于求以及商业化销售资源相对稀缺的背景下，项目合作开始逐步转向中晚期产品，III期临床的起始或成功完成成为越来越多的合作起点。在合作条件上，不确定性的增多以及市场竞争的复杂使得授权费和销售提成等要素触发的里程碑点设置更加细化，不同情况下的差异化收益逐步取代了供少于求局面下的一刀切模式，通过合作实现双赢、大家都有钱赚的思路逐渐深入人心，未来这一趋势仍将延续下去。买方市场主要由在美具备商业化销售能力的大中型公司组成，既包括了以Sandoz为代表的能研能产能卖的一条龙翘楚，也包括了以Amneal为代表的不能研产但能卖的新晋小分子仿制药公司，买方市场则更多的涵盖了具备研发和生产能力但无力或无意在美进行自售的中小型公司。在没有足够产品支撑情况下的销售团队自建带来的入不敷出和稳定性风险注定将成为那份不可承受之重。在注册方面，随着生物类似药产品申报数量在2023财年再创新高以及多个产品III期临床于去年的顺利完成，预计2024年的申报和获批数量都将进一步实现增长，涉及的分子种类在2023年实现突破的基础上也将继续拓展。新的一年里BsUFAIII（生物类似药用户付费法案）将进入实施周期内的第二个财年，2024财年生物类似药申请费、项目费和开发费(BPD)相比上一财年大幅下滑，其中开发费(BPD)中包括的初始BPD费、年度BPD费用和再激活费用均下降了79%，申请费下滑42%后临床类和非临床类产品申请费分别降至1018753美元和509377美元，项目费同样下滑42%降至177397美元，各项费用相比上年的大幅下滑反映了近年来尤其是去年生物类似药开发蓬勃发展的局面。在流通方面，FDA已经批准了8个具有自动替换资格的生物类似药，涵盖了雷珠单抗、阿达木单抗、甘精胰岛素以及还未有生物类似药上市的乌司奴单抗四种分子。在自动替换的实际执行过程中，各州的法律也不尽相同，例如新泽西等9个州仅允许患者使用替换的生物类似药费用低于原研产品时进行替换，除北卡和弗吉尼亚以外的剩余48个州均需要药师在替换时与开具处方的医生进行反馈，阿拉巴马等4个州仅在得到开具处方的医生许可的情况下才可以进行替换，总体来说自动替换在各州实际执行时依然存在一定的限制条件，同时目前被授予可互换资格的产品涉及的治疗领域的覆盖面还不够广泛。近年来生物类似药的高速渗透更多的体现在肿瘤领域，在以英夫利昔单抗为代表的其他非肿瘤领域的渗透速度依然还有不小的提升空间，医生在眼科等领域实际开具处方时对于生物类似药的使用依然比较谨慎，在一项针对80名眼科医生进行的调查中，80%的被调查者表示对生物类似药比较或非常熟悉，但其中仅有60%真正开具过生物类似药的处方，其中开具过雷珠单抗生物类似药Byooviz和Cimerli的比例均为40%。阿达木单抗在2023年表现的不及预期反映了此类主要在药房层面进行流通的产品受PBM覆盖影响的巨大，随着多家PBM在过去一年里逐渐将越来越多的生物类似药纳入覆盖清单，2024年生物类似药们的表现依然值得期待。在竞争方面，唯快不破的争取尽可能靠前的上市位次依然是决定竞争归属的最核心因素，在此基础上的差异化策略将进一步增加自身在竞争中的筹码，例如阿达木单抗的高浓度和可互换的多维度比拼、聚乙二醇化非格司亭自动注射器产品以及雷珠单抗预充式注射器产品的另辟蹊径。在复杂的生物类似药竞争中，单纯的价格杠杆调节很难做到像小分子领域那样屡试不爽，在争取到有利位次基础上的降价策略才更有意义。南来北往、有进有退，总体来看未来涉身美国生物类似药市场的公司数量仍呈上升趋势，竞争的格局将更加复杂和激烈，往事已成云烟，各方对于后续一波又一波陆续在中短期内失去专利保护的大药争夺又站在了同一起跑线上，孰强孰弱，拭目以待。在政策方面，美国政府层面对于推动生物类似药不断前进的努力一直在延续着。2023年2月，美国参议院司法委员会通过了一系列涉及生物类似药的立法，其中患者可负担处方药法案《Affordable Prescriptions for Patients Act of 2023》旨在防止制药公司利用专利制度来延迟仿制药和生物类似药的竞争，保留获得平价仿制药和生物类似药法案《Preserve Access to Affordable Generics and Biosimilars Act》将禁止品牌药公司在专利和解中向仿制药和生物类似药生产商支付费用以延迟竞争，停止拖延法案《Stop Stalling Act》旨在阻止品牌药商滥用FDA旨在确保药物安全的程序，法案将赋予联邦贸易委员会（FTC）更多权力（包括罚款）以对那些在FDA提起的试图干扰竞争性仿制药或生物类似药批准的“虚假公民请愿”采取行动，并促进对那些出于善意提出合理的公共卫生问题的请愿书进行有效审查。2023年7月，美国参议员 Mike Lee在其2022年提出的《生物类似药取消繁文缛节法案》被否决后再次提除了新版本的该法案，建议取消有关与开发生物类似药相关的转换研究的可互换性要求，该法案将在今年底再次被表决。千淘万漉虽辛苦, 吹尽狂沙始到金。行业的严冬终将过去，暂时的障碍不会永久，向阳而生，逆风而行，梦想定会实现。推荐阅读星条旗下的宝藏：美国生物类似药市场2022概览星条旗下的宝藏：美国生物类似药市场2021-2022概览星条旗下的宝藏：美国生物类似药市场2020概览星条旗下的宝藏：美国生物类似药概览（下）星条旗下的宝藏：2018美国化学仿制药市场概览Copyright © 2024 PHARMCUBE. 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生物类似药疫苗专利到期
2024-02-22
·医药魔方
肿瘤业务是制药巨头的“必争之地”，也诞生了多款重磅炸弹和超级重磅炸弹药物，2023年，K药（帕博利珠单抗）以250.11亿美元的年销售额荣登“药王”宝座；O药（纳武利尤单抗）也正式进入百亿美元超级重磅炸弹药物行列；强生多发性骨髓瘤新药达雷妥尤单抗距离100亿美元收入仅有一步之遥......有些产品尚处于攻城略地的青壮年时期，也有产品已逐渐走向生命周期尾端。伴随着专利悬崖的到来，蝉联多年小分子销售冠军的血液肿瘤药Revlimid（来那度胺）由于受到仿制药冲击，销售额呈断崖式下跌，2023年收入仅为60.97亿美元（-39%）。重磅炸弹的出现和退出也伴随着制药巨头肿瘤业务收入和排名的涨跌。2023年默沙东凭K药的强劲增势一举压过蝉联多年肿瘤收入TOP1的BMS，成为了新的肿瘤业务霸主。如今，全球肿瘤业务排名TOP10的制药巨头又都是谁呢？今天带大家一窥究竟。注：1. 肿瘤业务总收入以及主要产品收入单位：亿美元；2. 肿瘤业绩仅根据财报披露产品而统计NO.10 艾伯维Imbruvica（依布替尼）和Venclexta（维奈克拉）是艾伯维在肿瘤领域的两款核心产品。不过，由于市场竞争加剧等原因，Imbruvica销售收入近两年持续下滑，仅为35.96亿美元。作为首个上市的BTK抑制剂，Imbruvica不仅将面对阿卡替尼、泽布替尼的竞争，也将应付BTK C481S产品Jaypirca的挑战。作为全球上市的唯一一款Bcl-2抑制剂，Venclexta（维奈克拉）仍保持着双位数（13.9%）的增长，达到22.88亿美元。2023年，艾伯维血液肿瘤产品组合新添一款CD3/CD20双抗Epcoritamab，其于2023年5月获FDA批准用于治疗接受过二线或多线系统治疗的R/R DLBCL患者，上市半年就收获了3100万美元。2023年，艾伯维继续加码肿瘤领域，于年末豪掷101亿美金收购了ADC先驱ImmunoGen，获得其核心资产索米妥昔单抗以及一系列在研ADC候选药物，持续深耕ADC赛道。NO.9 礼来礼来曾经倚仗的产品Alimta（培美曲塞）在2021年到专利期后，销售额迅速萎缩，从20亿美元以上的重磅炸弹下跌至2023年的2.18亿美元。不过，乳腺癌药物Verzenio（阿贝西利）增势不可抵挡，达到38.63亿美元，增幅高达56%，是CDK4/6产品中增长潜力最好的产品。再加上Cyramza（雷莫芦单抗）、Tyvyt（信迪利单抗）、Erbitux（西妥昔单抗）等产品的贡献，2023年礼来肿瘤业务收入达到66.58亿美元，进入TOP10榜单。2023年，礼来肿瘤产品组合新增了一款BTK C481S抑制剂Jaypirca（pirtobrutinib），上市的首年获得了7500万美元的收入，前景可期。口服选择性雌激素受体降解剂（SERD）Imlunestrant的III期EMBER-3研究预计将于今年4月完成主要部分，有望今年在美日欧申报上市。NO.8 安进在Xgeva（地舒单抗）、Kyprolis（卡非佐米）、Vectibix（panitumumab）等老产品、肿瘤生物类似药Mvasi(贝伐珠单抗）、Vectibix（帕尼单抗）、Kanjinti（曲妥珠单抗）以及新产品Lumakras (sotorasib)、Blincyto（贝林妥欧单抗）的带动下，安进2023年肿瘤业务收入达到74.47亿美元。KRAS抑制剂Lumakras曾被寄予厚望，不过ODAC（肿瘤药物咨询委员会）会议上，专家们认为由于系统性偏倚问题，III期确证性研究CodeBreak 200主要终点PFS获益的可靠性不足。关于Lumakras是否会被要求退市的传言也曾一度甚嚣尘上。其2023年收入为2.8亿美元，与2022年基本持平。不过，安进拥有较为丰富的肿瘤管线储备，first in class的CD3/DLL3双抗Tarlatamab已递交治疗晚期小细胞肺癌的上市申请；first in class的CD3/STEAP1双抗Xaluritamig已获得治疗mCRPC的积极I期数据，另一款first in class的PRMT5分子胶正在开展I/II期研究。NO.7 辉瑞辉瑞肿瘤产品数量与BMS、罗氏等大户不相上下。不过，由于其缺少百亿美元或十亿美元以上的重磅产品，因此，肿瘤业务收入近些年一直不愠不火，2023年收入仅为116.27亿美元。辉瑞的当家品种Ibrance（哌柏西利）在CDK4/6市场的份额正被礼来和诺华攻占，2023年收入下跌了6%，ADC新药Besponsa（奥加伊妥珠单抗）和肾细胞癌药物Inlyta（阿昔替尼）均有小幅增长，但是后劲不足。不过Lorbrena（劳拉替尼）的表现尚可，实现了62%的增长，达到5.39亿美元。新冠光环褪去的辉瑞为了寻找下一个增长点，2023年以430亿美元的总交易额将ADC龙头企业Seagen收入麾下，囊获多款ADC产品，为此，辉瑞还成了新的肿瘤业务部门。到2030年，收购Seagen而得的产品有望为辉瑞创造百亿美元收入。NO.6 诺华2023年，诺华以135.9亿美元（+23%）的肿瘤业务收入超过辉瑞，排名前进1位。CDK4/6抑制剂Kisqali（瑞波西利，20.80亿美元，+75%）在2023年收获重要进展，辅助治疗早期乳腺癌III期NATALEE研究成功。基于此，诺华已向美国、欧洲和中国的监管部门递交新适应症上市申请。放射性配体疗法Pluvicto（9.80亿美元，+261%）和Lutathera增长势头迅猛，前者距离10亿美元大关只差一步之遥，后者也营收6.05亿美元（+28%）。产能受限是制约Pluvicto放量的一大因素，不过，今年1月FDA已批准诺华在印第安纳波利斯的生产基地进行Pluvicto的商业化生产。今年1月，Lutathera的III期NETTER-2研究也大获成功，与单独使用高剂量长效释放奥曲肽相比，Lutathera联合长效奥曲肽一线治疗可将生长抑素受体阳性高分化2级和3级晚期胃肠胰神经内分泌肿瘤患者的疾病进展或死亡风险降低72%。Scemblix（4.13亿美元，+179%）是一款STAMP变构抑制剂，于2021年在美国获批上市，用于治疗慢性髓系白血病。今年1月，Scemblix头对头一/二代TKIs III期ASC4FIRST研究也传来捷报。NO.5 阿斯利康 阿斯利康的肿瘤业务收入近几年持续增长，由2022年的146.3亿美元增长至2023年的171.45亿美元，主要依赖于Tagrisso（奥希替尼）、Imfinzi（度伐利尤单抗）、Lynparza（奥拉帕利）、Calquence（阿可替尼）、Enhertu（德曲妥珠单抗）等产品持续拉动。2023年阿斯利康肿瘤领域产品销售额（亿美元）作为全球重磅ADC，Enhertu的市场表现颇受业内关注。伴随着HER2低表达乳腺癌、HER2突变阳性NSCLC适应症在全球范围内的获批，Enhertu放量速度逐渐加快，2023年销售额同比翻了一番，其与第一三共共同记录的Enhertu全球收入已达到25.66亿美元。2023年，阿斯利康乳腺癌领域再添一员新将Truqap（Capivasertib）。作为全球首款AKT1/2/3高效选择性抑制剂，其上市仅一个多月，就收获了600万美元销售额。手握全球领先的ADC、肿瘤靶向治疗及免疫疗法资产，阿斯利康对于肿瘤业务的发展也有着清晰的方向，即在广泛的管线中不断解锁新组合。目前，阿斯利康正不遗余力推进IO+ADC组合。与此同时，2023年末，其通过收购中国Biotech亘喜生物正式切入CAR-T细胞疗法赛道。NO.4 强生 2023年强生肿瘤业务收入176.61亿美元（+10.5%），占其整个制药业务板块的32.3%。肿瘤业务收入虽稍逊色于自免业务收入（180.52亿美元，+6.6%）。不过，从增速上看，肿瘤业务大有赶超之势。肿瘤领域收入的增长主要归功于Darzalex（达雷妥尤单抗）、Erleada（阿帕他胺）、Imbruvica（伊布替尼）、Carvykti（西达基奥仑赛）等产品强劲驱动。其中，主力成员Darzalex得益于多发性骨髓瘤（MM）的全线程治疗，其市场份额持续扩大，2023年维持高增长态势（+22.2%），即将进入百亿美元俱乐部。前列腺癌治疗药物Zytiga(阿比特龙)销售额腰斩，仅有8.87美元的收入，不过接棒产品Erleada自上市以来一直保持双位增长趋势，2023年营收23.87亿美元（26.9%），成功晋级为强生前列腺癌领域一代新星。EGFR/c-MET双特异性抗体Rybrevant（Amivantamab）、BCMAxCD3双抗Teclistamab以及GPRC5DxCD3双抗Talquetamab已在近两年密集上市，不断壮大着强生肿瘤领域的竞争优势。NO.3 罗氏2023年，肿瘤依然是罗氏制药业务中收入最高的板块。罗氏曾经依仗的老“三驾马车”：Avastin（贝伐珠单抗）、Herceptin（曲妥珠单抗）和Rituxan（利妥昔单抗）虽在专利到期之后营收急速下降。可喜的是，Tecentriq（阿替利珠单抗）持续渗透、Kadcyla（恩美曲妥珠单抗）保持稳定销售表现，新产品Phesgo（曲妥珠单抗+帕妥珠单抗固定剂量复方）、Polivy（维泊妥珠单抗）和Gazyva（奥妥珠单抗）也开始接棒，罗氏全年肿瘤业绩营收基本与去年持平，达到190.87亿瑞士法郎（213.34亿美元）。罗氏凭借厚实的家底储备在肿瘤药市场依然牢牢占据领先地位。2023年，CD3/CD20双抗Columv成功获FDA加速批准上市，用于治疗既往接受过至少二线系统性治疗的复发或难治性DLBCL或由滤泡性淋巴瘤引起的LBCL成人患者；ALK抑制剂阿来替尼也有望今年在欧美地区扩展辅助治疗ALK阳性NSCLC新适应症。罗氏在研肿瘤项目多达近40个。其中，TIGTI单抗tiragolumab将在今年迎来历史性时刻，其联合阿替利珠单抗一线治疗PD-L1高表达NSCLC的III期SKYSCRAPER-01研究预计将于2024H2读出最终总生存期 (OS)数据，这一结果万众期待。NO.2 百时美施贵宝自收购新基以来，BMS始终在肿瘤领域位居全球制药巨头榜首，不过2023年，由于曾今的小分子销冠Revlimid（来那度胺）的断崖式销售下跌以及该领域成熟产品的表现均进入小步慢跑阶段，导致其痛失肿瘤业务TOP1的宝座。BMS肿瘤业务产品近5年销售额（亿美元）2023年，其新产品双免疫疗法Opdualag（relatlimab+nivolumab）在上市后的第2年便取得了6.27亿美元收入的好成绩，有望成为BMS又一款当家花旦。两款CAR-T细胞疗法产品正在持续发力，期望通过扩大生产规模，抢占市场。20年代后半段，BMS面临多款产品专利悬崖危机和新的政府强制定价压力，该公司也迎来了新任CEO Chris Boerner。为了应对重磅产品Opdivo即将到来的专利悬崖，以及巩固其在肿瘤领域的领导地位，BMS在2023年持续开展BD业务，完成了多起公司并购和项目交易，包括收购核药公司RayzeBio、与百利天恒就潜在FIC的HER3/EGFR双抗ADC产品达成独家许可与合作协议、收购Mirati从而获得该公司KRAS抑制剂以及产品管线等。NO.1 默沙东默沙东凭K药、Lynparza (奥拉帕尼)、Lenvima (仑伐替尼)、Welireg（belzutifan）以及Reblozyl（罗特西普）带来的合计276亿美元的销售收入，一举超过了BMS，成为了新晋肿瘤业务TOP1制药巨头。2023年默沙东肿瘤领域产品收入（亿美元）K药也将面临2028年专利悬崖危机。不过默沙东已经针对这一即将面临的挑战未雨绸缪，搭建了丰富的在研肿瘤管线。2023年，默沙东针对Keytruda新开了多项联合治疗III期临床研究，其中包括与肿瘤mRNA疫苗V940联合治疗NSCLC的两项研究，以及与TROP2 ADC新药MK-2870（从科伦博泰引进）联合一线治疗NSCLC的关键III期研究。除了继续挖掘Keytruda与其他疗法联合的治疗潜力，默沙东还计划通过增补肿瘤产品管线进一步丰富产品群来应对肿瘤业务可能面临的收入下滑情况。LSD1抑制剂Bomedemstat、BTK抑制剂Nemtabrutinib以及CYP11A1抑制剂MK-5684均被推向了III期临床。另外，默沙东正在开发K药皮下注射剂型，已于2023年2月开展了关键III期临床研究，预计将于2024年第3季度完成。来源：医药魔方NextPharma数据库除此之外，去年10月，默沙东还以高达220亿美元的总金额引进了第一三共3款ADC新药，其中patritumab deruxtecan上市申请已于2023年12月获得FDA优先审评，适应症为三线治疗EGFR突变NSCLC。今年，受益于ADC候选药物以及癌症疫苗，默沙东将其在研肿瘤学组合预估值提升到了200亿美元以上。由此看来，K药只是默沙东登顶肿瘤TOP1宝座的一个开始，未来会更精彩。 推荐阅读2023年全球制药巨头自免业务排名TOP102022年全球制药巨头肿瘤业务排名TOP102021年，全球肿瘤药巨头排名TOP102020年，全球肿瘤药巨头排名TOP10Copyright © 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抗体药物偶联物并购财报专利到期
2024-02-06
THOUSAND OAKS, Calif., Feb. 6, 2024 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced financial results for the fourth quarter and full year 2023 versus comparable periods in 2022.
"2023 was another year of performance and progress for our company," said Robert A. Bradway, chairman and chief executive officer. "Our marketed products are reaching many more patients around the world, and we anticipate more than a dozen significant pipeline milestones in 2024."
Key results include:
For the fourth quarter, total revenues increased 20% to $8.2 billion in comparison to the fourth quarter of 2022. Product sales grew 20%, driven by 23% volume growth, partially offset by 3% lower net selling price.
Nine brands(1) achieved record sales in the quarter, and Repatha® (evolocumab), EVENITY® (romosozumab-aqqg), Prolia® (denosumab) and BLINCYTO® (blinatumomab) delivered double-digit volume growth globally.
U.S. volume grew 26% and ex-U.S. volume grew 15%, including 46% volume growth in the Asia Pacific region.
Our performance included $954 million of sales for the period of Oct. 6 - Dec. 31 from our recent Horizon Therapeutics (Horizon) acquisition, driven by several first-in-class, early-in-lifecycle medicines such as TEPEZZA® (teprotumumab-trbw), KRYSTEXXA® (pegloticase) and UPLIZNA® (inebilizumab-cdon). Excluding the impact of these sales from Horizon, our product sales grew 5%, driven by volume growth of 9%.
For the full year, total revenues increased 7% to $28.2 billion, resulting from a 9% increase in product sales. Product sales growth was driven by 15% volume growth, partially offset by 3% lower net selling price, 1% unfavorable changes from estimated sales deductions and 1% negative impact from foreign exchange.
GAAP earnings per share (EPS) decreased 53% from $3.00 to $1.42 in the fourth quarter, driven by acquisition-related expenses and incremental operating expenses from Horizon, partially offset by increased revenues. For the full year, GAAP EPS increased 3% from $12.11 to $12.49 driven by net gains on our BeiGene, Ltd equity investment in 2023 and higher revenues, partially offset by higher operating expenses, including acquisition-related expenses and incremental expenses from Horizon.
For the fourth quarter, GAAP operating income decreased from $2.2 billion to $1.3 billion, and GAAP operating margin decreased 17.8 percentage points to 16.2%. For the full year, GAAP operating income decreased from $9.6 billion to $7.9 billion, and GAAP operating margin decreased 9.3 percentage points to 29.3%.
Non-GAAP EPS increased 15% from $4.09 to $4.71 in the fourth quarter and increased 5% from $17.69 to $18.65 for the full year, driven by increased revenues, partially offset by higher operating expenses, including incremental expenses from Horizon. Fourth quarter non-GAAP EPS was also unfavorably impacted by higher interest expense.
For the fourth quarter, non-GAAP operating income increased from $3.0 billion to $3.7 billion, and non-GAAP operating margin increased 0.8 percentage points to 46.7%. For the full year, non-GAAP operating income increased from $12.8 billion to $13.4 billion, and non-GAAP operating margin decreased 1.7 percentage points to 49.8%.
The Company generated $7.4 billion of free cash flow for the full year versus $8.8 billion in 2022. The decrease in 2023 was primarily driven by transaction expenses related to the Horizon acquisition and higher repatriation tax payments.
(1) Includes product sales for the full fourth quarter of 2023 from UPLIZNA and KRYSTEXXA in connection with Horizon acquisition.
References in this release to "non-GAAP" measures, measures presented "on a non-GAAP basis," "free cash flow" (computed by subtracting capital expenditures from operating cash flow), "EBITDA, or earnings before interest, taxes, depreciation and amortization" (computed by adding interest expense, provision for income taxes, and depreciation and amortization expense to GAAP net income) and "debt leverage ratio" (calculated as the ratio of GAAP total debt to EBITDA) refer to non-GAAP financial measures. Adjustments to the most directly comparable GAAP financial measures and other items are presented on the attached reconciliations. Refer to Non-GAAP Financial Measures below for further discussion.
Product Sales Performance
Total product sales increased 20% for the fourth quarter of 2023 versus the fourth quarter of 2022. Volume grew 23%, partially offset by 3% lower net selling price. Full year product sales increased 9% versus 2022, driven by 15% volume growth, partially offset by 3% lower net selling price, 1% unfavorable changes from estimated sales deductions and 1% negative impact from foreign exchange.
General Medicine
Repatha® sales increased 25% year-over-year for the fourth quarter, driven by 35% volume growth, partially offset by lower net selling price. Full year sales increased 26%, driven by 37% volume growth, partially offset by lower net selling price. Repatha remains the global proprotein convertase subtilisin/kexin type 9 (PCSK9) segment leader, with over 2.5 million patients treated since launch.
Prolia® sales increased 12% year-over-year, to a record $1.1 billion for the fourth quarter, and 12% for the full year, primarily driven by volume growth and higher net selling price. Volume grew 10% for the quarter and 9% for the full year. In 2023, over 7.5 million patients were treated with Prolia.
EVENITY® sales increased 41% year-over-year to a record $318 million for the fourth quarter and 47% for the full year, driven by strong volume growth. U.S. volume grew 44% year-over-year and volume outside the U.S. grew 55% for the full year.
Aimovig® (erenumab-aooe) sales decreased 32% year-over-year for the fourth quarter and 22% for the full year, driven by lower net selling price.
Oncology
BLINCYTO® sales increased 47% year-over-year to a record $241 million for the fourth quarter and 48% for the full year, driven by 55% and 49% volume growth, respectively. Volume growth was supported by broad prescribing across academic and community settings for patients with B-cell precursor acute lymphoblastic leukemia.
Vectibix® (panitumumab) sales increased 5% year-over-year for the fourth quarter and 10% for the full year, driven by 5% and 10% volume growth, respectively.
KYPROLIS® (carfilzomib) sales increased 8% year-over-year for the fourth quarter and 13% for the full year, driven by 8% and 12% volume growth, respectively.
LUMAKRAS®/LUMYKRAS™ (sotorasib) sales increased 8% year-over-year for the fourth quarter, driven by 5% volume growth and higher net selling price. Full year sales decreased 2%, driven by unfavorable changes to estimated sales deductions, including changes related to ongoing reimbursement negotiations in France. Full year sales were also impacted by lower net selling price and lower inventory levels, partially offset by 16% volume growth.
XGEVA® (denosumab) sales increased 9% year-over-year for the fourth quarter and 5% for the full year, primarily driven by higher net selling price.
Nplate® (romiplostim) sales decreased 18% year-over-year for the fourth quarter, driven by volume decline related to timing of orders placed by the U.S. government, partially offset by volume growth across our U.S. and ex-U.S. regions. U.S. government orders were $207 million in Q4'22 compared to $62 million in Q4'23. Full year sales increased 13%, primarily driven by volume growth, including U.S. government orders. U.S. government orders were $207 million for FY'22 compared to $286 million for FY'23. Excluding these U.S. government orders, Nplate sales grew 23% year-over-year for the fourth quarter and 8% for the full year.
MVASI® (bevacizumab-awwb) sales decreased 8% year-over-year for the fourth quarter, primarily driven by lower net selling price, partially offset by 12% volume growth. Full year sales decreased 11%, primarily driven by lower net selling price, partially offset by 13% volume growth. Going forward, we expect continued net selling price erosion driven by increased competition.
KANJINTI® (trastuzumab-anns) sales decreased 33% year-over-year for the fourth quarter and 50% for the full year, driven by lower net selling price and volume decline.
Inflammation
TEZSPIRE® (tezepelumab-ekko) generated $177 million of sales in the fourth quarter. Quarter-over-quarter sales increased 10%, driven by 18% volume growth that benefited from the pre-filled, single-use pen, which was approved for self-administration by the U.S. Food and Drug Administration (FDA) in the first quarter. Healthcare providers recognize TEZSPIRE's unique, differentiated profile and its broad potential to treat the 2.5 million patients worldwide with severe asthma who are uncontrolled, without any phenotypic or biomarker limitation.
Otezla® (apremilast) sales increased 2% year-over-year for the fourth quarter, driven by favorable changes to estimated sales deductions and 3% volume growth, partially offset by lower inventory levels and lower net selling price. Full year sales decreased 4%, driven by lower net selling price and lower inventory levels, partially offset by 2% volume growth.
We expect future growth for Otezla to be driven by its established efficacy and safety profile, strong payer coverage with limited prior authorization requirements and ease of administration. Otezla remains the only approved oral systemic therapy with a broad indication and is well-positioned to help the 1.5 million U.S. patients with mild-to-moderate psoriasis who cannot be optimally addressed by a topical and can benefit from a systemic treatment like Otezla.
Enbrel® (etanercept) sales decreased 8% year-over-year for the fourth quarter, driven by a 4% impact from unfavorable changes to estimated sales deductions and lower net selling price. Full year sales decreased 10%, driven by lower net selling price, lower inventory levels and a 3% impact from unfavorable changes to estimated sales deductions. Year-over-year volume remained flat, with U.S. volume growing 1% in the fourth quarter, supported by an increase in new patients starting treatment as a result of improved payer coverage. Going forward, we expect net selling price to continue to decline year-over-year, driven by higher rebates to maintain broad first-line payer coverage and changes in patient mix.
We expect Otezla and Enbrel to follow the historical pattern of lower sales in the first quarter relative to subsequent quarters due to the impact of benefit plan changes, insurance reverification and increased co-pay expenses as U.S. patients work through deductibles.
AMJEVITA®/AMGEVITA™ (adalimumab) sales increased 34% year-over-year for the fourth quarter and 36% for the full year, primarily driven by 35% and 46% volume growth, respectively. Ex-U.S. sales increased 9% for the full year, driven by 20% volume growth, partially offset by lower net selling price. U.S. sales increased 43% quarter-over-quarter, driven by higher inventory levels and higher net selling price, partially offset by volume decline.
Rare Disease
Excluding TAVNEOS®, the products listed below were acquired from our Horizon transaction on Oct. 6, 2023. Sales figures reflect only sales in the period from Oct. 6 2023 through the end of the year, and not the full quarter.
TEPEZZA® (teprotumumab-trbw) generated $448 million of sales for the period. TEPEZZA is the first and only FDA-approved treatment for thyroid eye disease (TED).
KRYSTEXXA® (pegloticase) generated $272 million of sales for the period. KRYSTEXXA is the first and only FDA-approved treatment for chronic refractory gout.
UPLIZNA® (inebilizumab-cdon) generated $65 million of sales for the period. UPLIZNA is used to treat adults with neuromyelitis optica spectrum disorders (NMOSD).
TAVNEOS® (avacopan) generated $44 million of sales in the fourth quarter. Quarter-over-quarter sales increased 19%, primarily driven by volume growth. U.S. volume grew 23% quarter-over-quarter. In the U.S., approximately 2,700 patients have now been treated with TAVNEOS.
Ultra rare products, which consist of
RAVICTI® (glycerol phenylbutyrate),
PROCYSBI® (cysteamine bitartrate),
ACTIMMUNE® (interferon gamma-1b),
BUPHENYL® (sodium phenylbutyrate) and
QUINSAIR® (levofloxacin) generated $164 million of sales for the period.
Established Products
Total sales of our established products, which consist of
EPOGEN® (epoetin alfa),
Aranesp® (darbepoetin alfa),
Parsabiv® (etelcalcetide) and
Neulasta® (pegfilgrastim), decreased 10% year-over-year for the fourth quarter, primarily driven by lower net selling price and volume declines, partially offset by favorable changes to estimated sales deductions. Full year sales decreased 19%, driven by lower net selling price and volume declines. In the aggregate, we expect the year-over-year net selling price and volume declines for this portfolio of products to continue.
Product Sales Detail by Product and Geographic Region
Operating Expense, Operating Margin and Tax Rate Analysis
On a GAAP basis:
Total Operating Expenses increased 50% year-over-year for the fourth quarter. For the full year, Total Operating Expenses increased 21%.
Cost of Sales as a percentage of product sales increased 13.0 percentage points in the fourth quarter primarily driven by higher amortization expense from acquisition-related assets as well as higher profit share and royalties, partially offset by Puerto Rico excise tax, changes in product mix, and lower manufacturing cost. For the full year, cost of sales as a percentage of product sales increased 5.6 percentage points primarily driven by higher amortization expense from acquisition-related assets, higher profit share and royalties, and changes in product mix, partially offset by Puerto Rico excise tax.
Research & Development (R&D) expenses increased 16% in the fourth quarter and increased 8% for the full year driven by higher spend in later-stage clinical programs and marketed products support, including spend from programs acquired from the Horizon acquisition.
Selling, General & Administrative (SG&A) expenses increased 45% in the fourth quarter and increased 14% for the full year primarily driven by higher acquisition-related costs, in addition to commercial and general administrative expenses related to the Horizon acquisition. For the full year, this was partially offset by a decline in other marketed product spend.
Other operating expenses for the full year consisted of net impairment charges for AMG 340 and Teneobio IPR&D assets in addition to expenses related to our restructuring plan initiated in the first quarter of 2023.
Operating Margin as a percentage of product sales decreased 17.8 percentage points to 16.2% in the fourth quarter and decreased 9.3 percentage points for the full year to 29.3%.
Tax Rate increased 2.4 percentage points in the fourth quarter and increased 3.7 percentage points for the full year, primarily driven by the 2022 Puerto Rico tax law change that replaced the excise tax with an income tax beginning in 2023. For the fourth quarter this was partially offset by the change in earnings mix.
On a non-GAAP basis:
Total Operating Expenses increased 18% for the fourth quarter and increased 9% for the full year.
Cost of Sales as a percentage of product sales remained flat in the fourth quarter primarily driven by higher profit share and royalties, offset by Puerto Rico excise tax, changes in product mix, and lower manufacturing cost. For the full year, cost of sales as a percentage of product sales increased 1.1 percentage points primarily driven by higher profit share and royalties and changes in product mix, partially offset by Puerto Rico excise tax.
R&D expenses increased 16% in the fourth quarter and increased 8% for the full year driven by higher spend in later-stage clinical programs and marketed products support, including spend from programs acquired from the Horizon acquisition.
SG&A expenses increased 20% in the fourth quarter and increased 5% for the full year primarily driven by higher commercial and general administrative expenses related to the Horizon acquisition. For the full year, this was partially offset by a decline in other marketed product spend.
Operating Margin as a percentage of product sales increased 0.8 pts. percentage points to 46.7% in the fourth quarter and decreased 1.7 percentage points for the full year to 49.8%.
Tax Rate increased 2.5 percentage points in the fourth quarter and increased 2.7 percentage points for the full year primarily due to the 2022 Puerto Rico tax law change that replaced the excise tax with an income tax beginning in 2023.
Cash Flow and Balance Sheet
The Company generated $0.3 billion of free cash flow in the fourth quarter of 2023 versus $2.3 billion in the fourth quarter of 2022, primarily driven by timing of federal and repatriation tax payments. The Company generated $7.4 billion of free cash flow for the full year 2023 versus $8.8 billion in 2022.
The Company's fourth quarter 2023 dividend of $2.13 per share was declared on October 24, 2023, and was paid on December 8, 2023, to all stockholders of record as of November 17, 2023, representing a 10% increase from 2022.
During the fourth quarter, there were no repurchases of shares of common stock.
Cash and investments totaled $10.9 billion and debt outstanding totaled $64.6 billion as of December 31, 2023. Debt leverage was approximately 4.4 times EBITDA as of December 31, 2023.
2024 Guidance
For the full year 2024, the Company expects:
Total revenues in the range of $32.4 billion to $33.8 billion.
On a
GAAP basis, EPS in the range of $8.42 to $9.87, and a
tax rate in the range of 11.5% to 13.0%.
On a
non-GAAP basis, EPS in the range of $18.90 to $20.30, and a
tax rate in the range of 16.0% to 17.0%.
Capital expenditures to be approximately $1.1 billion.
Share repurchases not to exceed $500 million.
Fourth
Quarter Product and Pipeline Update
The Company provided the following updates on selected product and pipeline programs:
General Medicine
Maridebart cafraglutide (AMG 133)
A Phase 2 study of maridebart cafraglutide, a multispecific molecule that inhibits the gastric inhibitory polypeptide receptor (GIPR) and activates the glucagon like peptide 1 (GLP-1) receptor, in overweight or obese adults with or without type 2 diabetes mellitus has completed enrollment, with topline data anticipated in late 2024. The Company recently added a Part 2 to this study which explores durable weight loss beyond 52 weeks.
Planning for a comprehensive Phase 3 program across multiple indications remains on track.
In February 2024, results of preclinical studies and the Phase 1 study of maridebart cafraglutide were published in Nature Metabolism.
AMG 786
A Phase 1 study of AMG 786, a small molecule obesity program, is ongoing with initial data readout anticipated in H1 2024. This molecule has a different target than maridebart cafraglutide and is not an incretin-based therapy.
Olpasiran (AMG 890)
A Phase 3 cardiovascular outcomes study of olpasiran, a potentially best-in-class small interfering ribonucleic acid (siRNA) molecule that reduces lipoprotein(a) (Lp(a)) synthesis in the liver, in patients with atherosclerotic cardiovascular disease and elevated Lp(a) continues to enroll patients. To date, over 7,000 patients have been enrolled, with enrollment completion anticipated in H1 2024.
Repatha
EVOLVE-MI, a Phase 4 study of Repatha administered within 10 days of an acute myocardial infarction to reduce the risk of cardiovascular events, continues to enroll patients.
A Phase 3 cardiovascular outcomes study (VESALIUS-CV) in patients at high cardiovascular risk without prior myocardial infarction or stroke is ongoing.
Oncology
Tarlatamab (AMG 757)
The U.S. Food and Drug Administration (FDA) has granted Priority Review for the Company's Biologics License Application (BLA) for tarlatamab, a first-in-class investigational delta-like ligand 3 (DLL3) targeting BiTE® (bispecific T-cell engager) molecule. The BLA is based on the results from the Phase 2 DeLLphi-301 clinical trial, which demonstrated antitumor activity with a durable response and encouraging survival outcomes in previously treated small cell lung cancer (SCLC). The safety profile was consistent with the Phase 1 trial. Based on the Priority Review designation, the Prescription Drug User Fee Act (PDUFA) date for tarlatamab is June 12, 2024.
DeLLphi-304, a Phase 3 study comparing tarlatamab with standard of care chemotherapy in second-line SCLC, continues to enroll patients.
DeLLphi-306, a Phase 3 study comparing tarlatamab with placebo in limited-stage SCLC, was initiated.
DeLLphi-305, a Phase 3 study comparing tarlatamab and durvalumab with durvalumab alone in first-line, extensive-stage SCLC, will be initiated in H1 2024.
DeLLphi-300, a Phase 1 study of tarlatamab in relapsed/refractory SCLC, continues to enroll patients.
DeLLphi-302, a Phase 1b study of tarlatamab in combination with AMG 404, an anti-programmed cell death protein 1 (PD1) monoclonal antibody, in second-line or later SCLC, is ongoing.
DeLLphi-303, a Phase 1b study of tarlatamab in combination with standard of care in first-line SCLC, continues to enroll patients.
DeLLpro-300, a Phase 1b study of tarlatamab in de novo or treatment-emergent neuroendocrine prostate cancer, is ongoing.
BLINCYTO
The FDA granted Priority Review for the Company's supplemental BLA for BLINCYTO in early-stage, CD19-positive B-cell precursor acute lymphoblastic leukemia (B-ALL) based in part on the Phase 3 E1910 study conducted by the National Cancer Institute, the Eastern Cooperative Oncology Group and the American College of Radiology Imaging Network Cancer Research Group. Based on the Priority Review designation, the PDUFA date for BLINCYTO is June 21, 2024. Additional global regulatory authority submissions are underway.
Golden Gate, a Phase 3 study of BLINCYTO alternating with low-intensity chemotherapy in older adults with newly diagnosed Philadelphia chromosome-negative (Ph-) B-ALL, continues to enroll patients.
The Company is planning to amend the Golden Gate Phase 3 study to include an evaluation of blinatumomab subcutaneous administration with initiation anticipated in H2 2024.
A Phase 1/2 study of subcutaneous blinatumomab in adults with relapsed or refractory Ph- B-ALL continues to enroll patients.
Xaluritamig (AMG 509)
A Phase 1b monotherapy and combination dose-escalation and -expansion study of xaluritamig, a first-in-class bispecific T-cell engager targeting six-transmembrane epithelial antigen of prostate 1 (STEAP1) in metastatic castrate resistant prostate cancer continues to enroll patients in the dose-expansion portion of the study, where enrollment is almost complete. A reduced monitoring cohort was also initiated.
Two additional Phase 1 studies of xaluritamig to evaluate preliminary efficacy and safety in patients with early prostate cancer are planned.
AMG 193
The Phase 1/1b/2 study of AMG 193, a first-in-class small molecule methylthioadenosine (MTA)-cooperative protein arginine methyltransferase 5 (PRMT5) inhibitor, continues to enroll patients with advanced methylthioadenosine phosphorylase (MTAP)-null solid tumors. To date, responses have been seen in nine patients across seven tumor types.
Master protocols in thoracic and gastrointestinal malignancies exploring combinations with standard of care will be initiated in H1 2024.
A Phase 1/2 study of AMG 193 in combination with IDE397, an investigational methionine adenosyltransferase 2A (MAT2A) inhibitor, is enrolling patients.
Nplate
A Phase 3 study of Nplate in chemotherapy-induced thrombocytopenia in gastrointestinal, pancreatic, or colorectal malignancies is fully enrolled. Data readout is anticipated in H2 2024.
LUMAKRAS/LUMYKRAS
A U.S. regulatory submission is planned for the Phase 3 CodeBreaK 300 trial in H1 2024. This study evaluated two doses of LUMAKRAS (960 mg or 240 mg) in combination with Vectibix in patients with chemorefractory KRAS G12C-mutated metastatic colorectal cancer (CRC).
A Phase 3 study of LUMAKRAS in combination with Vectibix and FOLFIRI in first-line KRAS G12C-mutated CRC was initiated.
A Phase 3 study of LUMAKRAS plus chemotherapy vs. pembrolizumab plus chemotherapy in first-line KRAS G12C-mutated and programmed cell death protein ligand-1 (PD-L1) negative advanced non-small cell lung cancer (NSCLC) is enrolling patients.
Regulatory review by the European Medicines Agency (EMA) of the CodeBreaK 200 Phase 3 trial of adults with previously treated locally advanced or metastatic KRAS G12C-mutated NSCLC along with data from the Phase 2 dose-comparison substudy is ongoing.
The FDA completed its review of the Company's supplemental New Drug Application seeking full approval of LUMAKRAS based on the CodeBreaK 200 trial results. The FDA issued a new postmarketing requirement for an additional confirmatory study to support full approval to be completed no later than February 2028, while also concluding that LUMAKRAS at 960 mg once-daily will remain the dose for patients with KRAS G12C-mutated NSCLC under accelerated approval.
Bemarituzumab
FORTITUDE-101, a Phase 3 study of bemarituzumab, a first-in-class fibroblast growth factor receptor 2b (FGFR2b) targeting monoclonal antibody, plus chemotherapy in first-line gastric cancer, continues to enroll patients.
FORTITUDE-102, a Phase 1b/3 study of bemarituzumab plus chemotherapy and nivolumab in first-line gastric cancer, continues to enroll patients in the Phase 3 portion of the study.
FORTITUDE-103, a Phase 1b/2 study of bemarituzumab plus oral chemotherapy regimens with or without nivolumab in first-line gastric cancer, continues to enroll patients.
FORTITUDE-301, a Phase 1b/2 basket study of bemarituzumab monotherapy in solid tumors with FGFR2b overexpression, is ongoing.
Inflammation
TEZSPIRE
In severe asthma, the WAYFINDER Phase 3b study is fully enrolled. The PASSAGE Phase 4 real-world effectiveness study and the SUNRISE Phase 3 study continue to enroll patients.
A Phase 3 study of TEZSPIRE in chronic rhinosinusitis with nasal polyps is fully enrolled. Primary analysis is anticipated in H2 2024.
A Phase 3 study of TEZSPIRE in eosinophilic esophagitis continues to enroll patients.
A Phase 2 study of TEZSPIRE in chronic obstructive pulmonary disease is fully enrolled. Data readout is anticipated in H1 2024.
Rocatinlimab (AMG 451/KHK4083)
The ROCKET Phase 3 program, now composed of eight studies evaluating rocatinlimab, a first in class monoclonal antibody targeting OX40, in moderate to severe atopic dermatitis, continues to enroll adult and adolescent patients. To date, over 2,400 patients have been enrolled in the ROCKET program.
The Phase 3 HORIZON study (part of the ROCKET program) evaluating rocatinlimab monotherapy vs. placebo in adults with moderate to severe atopic dermatitis is fully enrolled. Data readout is anticipated in H2 2024.
A Phase 2 study of rocatinlimab in asthma will be initiated in H1 2024 and a Phase 3 study of rocatinlimab in prurigo nodularis will be initiated in H2 2024.
Otezla
In November 2023, data were presented from the MOSAIC and FOREMOST studies:
In the MOSAIC Phase 4 study, primary and key secondary outcomes highlighted that Otezla led to better inflammatory disease control in psoriatic arthritis patients with moderate clinical disease activity than in patients with high disease activity.
In the FOREMOST Phase 4 study, Otezla when added to standard of care, significantly improved disease activity in patients with early oligoarticular (few joints involved) psoriatic arthritis at 16 weeks compared to placebo.
Efavaleukin alfa (AMG 592)
A Phase 2b study of efavaleukin alfa, an interleukin 2 (IL 2) mutein Fc fusion protein, in ulcerative colitis continues to enroll patients.
Ordesekimab (AMG 714/PRV-015)
A Phase 2b study of AMG 714, a monoclonal antibody that binds interleukin-15, in nonresponsive celiac disease has completed enrollment.
Rare Disease
TAVNEOS
In November 2023, data were presented from the Phase 3 ADVOCATE trial demonstrating that outcomes in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis favored TAVNEOS versus a prednisone taper across subgroups of patients 65 years and older, patients with kidney involvement and albuminuria, and patients with diffuse alveolar hemorrhage at baseline.
TEPEZZA
In December 2023, TEPEZZA received orphan drug designation in Japan for patients with moderate to severe active thyroid eye disease (TED).
A New Drug Application was submitted for TEPEZZA in Japan based on the results from the OPTIC-J study evaluating TEPEZZA in patients with active TED.
A Phase 3 study of TEPEZZA in Japan for chronic or low clinical activity score (CAS) TED continues to enroll patients.
The Company plans to initiate a Phase 3 study evaluating the subcutaneous route of administration of TEPEZZA in patients with TED in H1 2024.
UPLIZNA
A Phase 3 study of UPLIZNA in myasthenia gravis is fully enrolled. Data readout is anticipated in H2 2024.
A Phase 3 study of UPLIZNA for the prevention of flare in immunoglobulin G4- (IgG4) related disease is fully enrolled. Data readout is anticipated in H2 2024.
Dazodalibep
A Phase 3 study of dazodalibep, a cluster of differentiation 40 (CD40) ligand inhibitor fusion protein in Sjögren's syndrome is enrolling patients.
Daxdilimab
A Phase 2 study of daxdilimab, a fully human monoclonal antibody targeting immunoglobulin-like transcript 7 (ILT7), in moderate-to-severe active primary discoid lupus erythematosus refractory to standard of care is enrolling patients.
A Phase 2 study of daxdilimab in dermatomyositis and antisynthetase inflammatory myositis is enrolling patients.
Fipaxalparant (formerly AMG 670 / HZN 825)
A Phase 2 study of fipaxalparant, a lysophosphatidic acid receptor 1 (LPAR1) antagonist, in idiopathic pulmonary fibrosis is enrolling patients. Data readout is anticipated in H2 2024.
A Phase 2 study of fipaxalparant in diffuse cutaneous systemic sclerosis is enrolling patients.
Biosimilars
The clinical comparative study portion of a randomized, double-blind pivotal study evaluating pharmacokinetic (PK) similarity of ABP 206 compared with OPDIVO® (nivolumab) in resected stage III or stage IV melanoma patients in the adjuvant setting is enrolling patients.
TEZSPIRE is being developed in collaboration with AstraZeneca.
Rocatinlimab, formerly AMG 451/KHK4083, is being developed in collaboration with Kyowa Kirin.
Ordesekimab, formerly AMG 714 and also known as PRV-015, is being developed in collaboration with Provention Bio, a Sanofi Company. For the purposes of the collaboration, Provention Bio conducts a clinical trial and leads certain development and regulatory activities for the program.
Xaluritamig, formerly AMG 509, is being developed pursuant to a research collaboration with Xencor, Inc.
IDE397 is an investigational MAT2A inhibitor from IDEAYA Biosciences.
OPDIVO is a registered trademark of Bristol-Myers Squibb Company.
Non-GAAP Financial Measures
In this news release, management has presented its operating results for the fourth quarters and full years of 2023 and 2022, in accordance with U.S. Generally Accepted Accounting Principles (GAAP) and on a non-GAAP basis. In addition, management has presented its full year 2024 EPS and tax guidance in accordance with GAAP and on a non-GAAP basis. These non-GAAP financial measures are computed by excluding certain items related to acquisitions, divestitures, restructuring and certain other items from the related GAAP financial measures. Beginning January 1, 2022, following industry guidance from the U.S. Securities and Exchange Commission, the Company no longer excludes adjustments for upfront license fees, development milestones and in-process research and development (IPR&D) expenses of pre-approval programs related to licensing, collaboration and asset acquisition transactions from its non-GAAP financial measures. Management has presented Free Cash Flow (FCF), which is a non-GAAP financial measure, for the fourth quarters and full years of 2023 and 2022. FCF is computed by subtracting capital expenditures from operating cash flow, each as determined in accordance with GAAP. Management has also presented Earnings Before Interest, Taxes, Depreciation and Amortization (EBITDA) and debt leverage ratio for 2023, both of which are non-GAAP financial measures. EBITDA is computed by adding interest expense, provision for income taxes, and depreciation and amortization expense to GAAP net income. Debt leverage ratio is calculated as the ratio of GAAP total debt to EBITDA.
The Company believes that its presentation of non-GAAP financial measures provides useful supplementary information to and facilitates additional analysis by investors. The Company uses certain non-GAAP financial measures to enhance an investor's overall understanding of the financial performance and prospects for the future of the Company's normal and recurring business activities by facilitating comparisons of results of normal and recurring business operations among current, past and future periods. The Company believes that FCF provides a further measure of the Company's liquidity. The Company believes its debt leverage ratio provides a supplemental operating metric for the full year period as it compares the amount of cash generated by our operations for the year.
The Company uses the non-GAAP financial measures set forth in the news release in connection with its own budgeting and financial planning internally to evaluate the performance of the business, including to allocate resources and to evaluate results relative to incentive compensation targets. The non-GAAP financial measures are in addition to, not a substitute for, or superior to, measures of financial performance prepared in accordance with GAAP.
About Amgen
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.
Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world's leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.
Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average and is also part of the Nasdaq-100 index. In 2023, Amgen was named one of "America's Greatest Workplaces" by Newsweek, one of "America's Climate Leaders" by USA Today and one of the "World's Best Companies" by TIME.
For more information, visit Amgen.com and follow us on X (formerly known as Twitter), LinkedIn, Instagram, TikTok, YouTube and Threads.
Forward-Looking Statements
This news release contains forward-looking statements that are based on the current expectations and beliefs of Amgen. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including any statements on the outcome, benefits and synergies of collaborations, or potential collaborations, with any other company (including BeiGene, Ltd. or Kyowa Kirin Co., Ltd.), the performance of Otezla® (apremilast) (including anticipated Otezla sales growth and the timing of non-GAAP EPS accretion), our acquisitions of Teneobio, Inc., ChemoCentryx, Inc., or Horizon (including the prospective performance and outlook of Horizon's business, performance and opportunities and any potential strategic benefits, synergies or opportunities expected as a result of such acquisition, and any projected impacts from the Horizon acquisition on our acquisition-related expenses going forward), as well as estimates of revenues, operating margins, capital expenditures, cash, other financial metrics, expected legal, arbitration, political, regulatory or clinical results or practices, customer and prescriber patterns or practices, reimbursement activities and outcomes, effects of pandemics or other widespread health problems on our business, outcomes, progress, and other such estimates and results. Forward-looking statements involve significant risks and uncertainties, including those discussed below and more fully described in the Securities and Exchange Commission reports filed by Amgen, including our most recent annual report on Form 10-K and any subsequent periodic reports on Form 10-Q and current reports on Form 8-K. Unless otherwise noted, Amgen is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.
No forward-looking statement can be guaranteed and actual results may differ materially from those we project. Our results may be affected by our ability to successfully market both new and existing products domestically and internationally, clinical and regulatory developments involving current and future products, sales growth of recently launched products, competition from other products including biosimilars, difficulties or delays in manufacturing our products and global economic conditions. In addition, sales of our products are affected by pricing pressure, political and public scrutiny and reimbursement policies imposed by third-party payers, including governments, private insurance plans and managed care providers and may be affected by regulatory, clinical and guideline developments and domestic and international trends toward managed care and healthcare cost containment. Furthermore, our research, testing, pricing, marketing and other operations are subject to extensive regulation by domestic and foreign government regulatory authorities. We or others could identify safety, side effects or manufacturing problems with our products, including our devices, after they are on the market. Our business may be impacted by government investigations, litigation and product liability claims. In addition, our business may be impacted by the adoption of new tax legislation or exposure to additional tax liabilities. If we fail to meet the compliance obligations in the corporate integrity agreement between us and the U.S. government, we could become subject to significant sanctions. Further, while we routinely obtain patents for our products and technology, the protection offered by our patents and patent applications may be challenged, invalidated or circumvented by our competitors, or we may fail to prevail in present and future intellectual property litigation. We perform a substantial amount of our commercial manufacturing activities at a few key facilities, including in Puerto Rico, and also depend on third parties for a portion of our manufacturing activities, and limits on supply may constrain sales of certain of our current products and product candidate development. An outbreak of disease or similar public health threat, such as COVID-19, and the public and governmental effort to mitigate against the spread of such disease, could have a significant adverse effect on the supply of materials for our manufacturing activities, the distribution of our products, the commercialization of our product candidates, and our clinical trial operations, and any such events may have a material adverse effect on our product development, product sales, business and results of operations. We rely on collaborations with third parties for the development of some of our product candidates and for the commercialization and sales of some of our commercial products. In addition, we compete with other companies with respect to many of our marketed products as well as for the discovery and development of new products. Discovery or identification of new product candidates or development of new indications for existing products cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate or development of a new indication for an existing product will be successful and become a commercial product. Further, some raw materials, medical devices and component parts for our products are supplied by sole third-party suppliers. Certain of our distributors, customers and payers have substantial purchasing leverage in their dealings with us. The discovery of significant problems with a product similar to one of our products that implicate an entire class of products could have a material adverse effect on sales of the affected products and on our business and results of operations. Our efforts to collaborate with or acquire other companies, products or technology, and to integrate the operations of companies or to support the products or technology we have acquired, may not be successful. There can be no guarantee that we will be able to realize any of the strategic benefits, synergies or opportunities arising from the Horizon acquisition, and such benefits, synergies or opportunities may take longer to realize than expected. We may not be able to successfully integrate Horizon, and such integration may take longer, be more difficult or cost more than expected. A breakdown, cyberattack or information security breach of our information technology systems could compromise the confidentiality, integrity and availability of our systems and our data. Our stock price is volatile and may be affected by a number of events. Our business and operations may be negatively affected by the failure, or perceived failure, of achieving our environmental, social and governance objectives. The effects of global climate change and related natural disasters could negatively affect our business and operations. Global economic conditions may magnify certain risks that affect our business. Our business performance could affect or limit the ability of our Board of Directors to declare a dividend or our ability to pay a dividend or repurchase our common stock. We may not be able to access the capital and credit markets on terms that are favorable to us, or at all.
###
CONTACT: Amgen, Thousand Oaks
Jessica Akopyan, 805-440-5721 (media)
Justin Claeys, 805-313-9775 (investors)
* The known adjustments are presented net of their related tax impact, which amount to approximately $2.60 per share.
(a) The adjustments include noncash amortization of intangible assets and fair value step-up of inventory acquired in business combinations.
Our GAAP diluted EPS guidance does not include the effect of GAAP adjustments triggered by events that may occur subsequent to this press release such as acquisitions, asset impairments, litigation, changes in fair value of our contingent consideration obligations and changes in fair value of our equity investments.
SOURCE Amgen
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研发状态
| 适应症 | 最高研发状态 | 国家/地区 | 公司 |
|---|---|---|---|
| 卵巢癌 | 批准上市 | 日本 更多 | |
| 胶质瘤 | 批准上市 | 日本 更多 | |
| 原发性腹膜癌 | 批准上市 | 美国 更多 | |
| 复发性乳腺癌 | 批准上市 | 日本 更多 | |
| 输卵管癌 | 批准上市 | 美国 更多 |
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临床结果
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适应症
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| 研究 | 分期 | 人群特征 | 评价人数 | 分组 | 结果 | 评价 | 发布日期 |
|---|
N/A | 三线 | - | (簾壓膚觸製鬱鑰顧衊艱) = 窪製齋獵觸廠鹹鏇簾艱 獵窪繭蓋鹹蓋醖艱鬱鬱 (網鹹糧網憲繭遞膚壓網 ) 更多 | - | 2016-12-06 | ||
(簾壓膚觸製鬱鑰顧衊艱) = 鹹廠壓構網壓鑰築夢鑰 獵窪繭蓋鹹蓋醖艱鬱鬱 (網鹹糧網憲繭遞膚壓網 ) 更多 | |||||||
N/A | 2,624 | EGFRIs plus doublet CT | (獵積餘壓鹽選膚鹹獵襯): OR = 1.72 (95% CI, 1.36 ~ 2.17) 更多 | 积极 | 2023-12-02 | ||
bevacizumab plus doublet CT | |||||||
N/A | - | 48 | (夢醖廠艱構簾鹽夢構醖) = 醖願蓋壓蓋鏇遞獵膚餘 範製鑰艱獵壓醖獵顧夢 (蓋獵鑰網簾選淵憲願獵 ) 更多 | - | 2017-10-17 | ||
(夢醖廠艱構簾鹽夢構醖) = 襯壓簾艱鹽鹹鑰齋夢艱 範製鑰艱獵壓醖獵顧夢 (蓋獵鑰網簾選淵憲願獵 ) 更多 | |||||||
临床3期 | 642 | (醖築壓遞鹹糧艱繭鹽製) = 簾糧廠壓鹽夢築衊鏇衊 壓選膚繭積艱壓積壓構 (窪窪顧網蓋淵膚壓齋觸 ) | 积极 | 2019-05-26 | |||
Bevacizumab reference product | (醖築壓遞鹹糧艱繭鹽製) = 艱襯淵鬱顧鏇範鏇糧糧 壓選膚繭積艱壓積壓構 (窪窪顧網蓋淵膚壓齋觸 ) | ||||||
N/A | 转移性结直肠癌 一线 | 239 | 積築鹹遞齋繭鹹膚壓憲(積夢觸鑰願艱鹽艱壓網) = At least one safety event of interest (EOI) was recorded for 26/75 (34.7%) wave 1 and 70/164 (42.7%) wave 2 patients 選顧簾壓夢醖窪築範淵 (鏇構鬱遞構構遞廠簾鹹 ) | - | 2023-05-31 | ||
ASCO2022 人工标引  | N/A | 1,445 | (觸構願選餘網艱築夢鏇) = 齋憲餘鏇鹽願範餘襯齋 衊網憲艱膚餘遞鏇鹹顧 (糧餘廠淵鹽鹹夢鹹獵選 ) 更多 | 非劣 | 2022-06-02 | ||
(觸構願選餘網艱築夢鏇) = 艱淵艱築構夢壓壓簾觸 衊網憲艱膚餘遞鏇鹹顧 (糧餘廠淵鹽鹹夢鹹獵選 ) 更多 | |||||||
临床2期 | RAS 野生型结直肠癌 RAS wild-type | 40 | FOLFOX plus panitumumab | (艱願憲淵膚淵餘遞範觸) = 淵鬱觸繭廠餘獵構膚觸 艱鹹願糧廠夢製蓋醖選 (願鏇築膚鹽糧憲廠膚顧 ) | 积极 | 2020-09-17 | |
FOLFOX plus bevacizumab | (艱願憲淵膚淵餘遞範觸) = 夢膚顧齋鹽獵鑰範壓窪 艱鹹願糧廠夢製蓋醖選 (願鏇築膚鹽糧憲廠膚顧 ) 更多 | ||||||
N/A | 非小细胞肺癌 一线 | 642 | (範衊膚壓襯願簾膚選窪) = 淵顧築醖築憲繭觸窪範 膚選夢獵廠衊淵憲繭窪 (淵襯範製獵廠艱製艱鏇, 0.80 ~ 1.09) 更多 | 积极 | 2016-12-06 | ||
(範衊膚壓襯願簾膚選窪) = 壓製繭遞選醖鏇觸衊齋 膚選夢獵廠衊淵憲繭窪 (淵襯範製獵廠艱製艱鏇 ) 更多 | |||||||
N/A | 800 | EGFRi plus doublet chemotherapy | (顧醖積鬱壓簾顧遞糧製) = 鹽膚憲淵窪製餘膚鬱遞 鹹鬱糧積簾憲網顧鹹餘 (鬱齋廠夢願餘積齋鏇製 ) | 积极 | 2022-07-02 | ||
Bevacizumab plus doublet chemotherapy | (顧醖積鬱壓簾顧遞糧製) = 夢選遞艱鏇築積繭膚鹽 鹹鬱糧積簾憲網顧鹹餘 (鬱齋廠夢願餘積齋鏇製 ) | ||||||
临床3期 | 非小细胞肺癌 一线 | 642 | 蓋製鏇齋網醖鏇鹹餘醖(壓壓醖選願顧積鹹鹽遞) = During the study, 4 (1.4%) and 7 (2.5%) patients in the ABP 215 and BEV group, respectively, developed binding antibodies; no patient tested positive for neutralizing antibodies. 範鏇憲鑰醖繭齋艱選積 (醖襯窪齋繭淵積衊築衊 ) | 积极 | 2017-05-30 | ||
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