A Phase 3, Randomized, Double-masked, Placebo-controlled, Parallel-group, Multicenter Trial to Evaluate the Efficacy, Safety and Tolerability of Subcutaneous Teprotumumab in Participants With Moderate-to-Severe Active Thyroid Eye Disease

The study consists of a randomized double-masked, placebo-controlled, parallel-group, multicenter trial with an optional open-label treatment period for proptosis non-responders who complete the Double-masked Treatment Period.

开始日期2024-02-21

申办/合作机构

Horizon Therapeutics USA, Inc.

JPRN-jRCT2031220730 / Recruiting临床3期

A Phase 3, Randomized, Double-masked, Placebo-controlled, Parallel-group Multicenter Trial to Evaluate the Efficacy and Safety of HZN-001 in Treating Japanese Participants with Chronic (Inactive) Thyroid Eye Disease

开始日期2023-03-29

申办/合作机构-

NCT04478994 / Terminated临床1期

A Randomized, Double-Blind, Placebo-Controlled, Repeat-Dose, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics, and Explore Efficacy of TEPEZZA in Patients With Diffuse Cutaneous Systemic Sclerosis

The overall objective is to investigate the safety, tolerability and effect on insulin-like growth factor-1 (IGF-1), inflammatory and fibrotic biomarkers of TEPEZZA (teprotumumab-trbw, HZN-001), a fully human monoclonal antibody (mAb) inhibitor of the IGF-1 receptor (IGF-1R), administered once every 3 weeks (q3W) for 24 weeks in the treatment of participants with diffuse cutaneous systemic sclerosis (dcSSc).

开始日期2021-11-17

申办/合作机构

Horizon Therapeutics USA, Inc.

100 项与替妥木单抗相关的临床结果

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100 项与替妥木单抗相关的转化医学

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100 项与替妥木单抗相关的专利（医药）

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245

项与替妥木单抗相关的文献（医药）

2024-03-01·Journal of Neuro-Ophthalmology

Real-World Experience With Teprotumumab in Patients With Dysthyroid Optic Neuropathy

Review

作者: Chen, Yuanyuan ; Tamhankar, Madhura A ; Briceño, César A ; Pradeep, Tejus

Background::

Teprotumumab, an insulin-like growth factor I receptor inhibitory antibody, improved proptosis, diplopia, inflammatory signs/symptoms, and quality of life in patients with active thyroid eye disease (TED) in clinical trials. The trials excluded patients with dysthyroid optic neuropathy (DON). Recently, many case reports and case series have reported the successful use of teprotumumab to treat DON. Here, we review the data from published cases and our clinical experience in treating patients having DON with teprotumumab.

Methods::

A literature search was conducted of patients with DON treated with teprotumumab from January 2020 through September 2022. Data from DON patients from the authors' (M.A.T. and C.A.B.) clinical practice were included. Primary outcome measure was mean (SD) improvements for visual acuity, color vision, and visual fields. Improvements in proptosis and clinical activity score (CAS) and diplopia were compared before and after teprotumumab administration.

Results::

Ten observational studies/case reports were identified along with 2 patients in our practice. In all, there were 24 active TED patients with DON (37 eyes) who were treated with teprotumumab. Mean (SD) age was 66.5 (13.6) years and 13 (54%) were females, disease duration ranged from 2 months to >15 years. 22/24 patients had none, minimal improvement or progression of visual loss with intravenous/oral corticosteroids, orbital decompression (n = 9), and orbital radiation (n = 2). There were 2 patients who received teprotumumab as the only therapy. Overall, 88% (21/24) reported improvement in visual acuity after teprotumumab and in 75% (18/24), improvement in vision was observed after just 2 infusions of teprotumumab. Three eyes had decompression surgery in close proximity to teprotumumab infusions and were excluded from analyses. Mean (SD) improvement in visual acuity was 3.73 lines (SD 3.74), range 2–15 lines in 33 eyes. The mean (SD) improvement in the mean deviation on visual field testing in 15 eyes was 5.6 db (3.0 db). Mean (SD) improvement in proptosis was 4.37 mm (SD: 2.11) (20 patients, 32 eyes); and clinical activity score: mean reduction of 5.1 (1.3) for 18 patients. Teprotumumab was well tolerated in all but one patient. Adverse events reported included fatigue, dysgeusia, hearing loss, nausea, hyperglycemia, and muscle spasms.

Conclusions::

Teprotumumab is an effective treatment for DON in our experience and in published cases in whom treatment with steroids, surgery, or orbital radiation was unsuccessful.

2024-01-01·Ophthalmology

Frequency and Patterns of Hearing Dysfunction in Patients Treated with Teprotumumab

Review

作者: Correa, Tatiana ; Shriver, Erin M ; Hansen, Marlan R ; Keen, Jamie A ; Pham, Chau ; Carter, Keith D ; Claussen, Alexander D

PURPOSE:

To better characterize the frequency and patterns of hearing dysfunction in patients who have received teprotumumab to treat thyroid eye disease.

DESIGN:

Noncomparative case series.

PARTICIPANTS:

Patients who underwent audiology testing before and after completion of teprotumumab infusions.

METHODS:

A review of patients who underwent audiology testing before and after completion of teprotumumab infusions was carried out. Additional audiogram testing during treatment was included when available. Hearing function was analyzed using audiogram data measuring threshold hearing levels at specific frequencies. Basic demographic data as well as information regarding otologic symptoms also were obtained and analyzed.

MAIN OUTCOME MEASURES:

Hearing loss demonstrated by a significant change in decibel hearing thresholds or that meets criteria for ototoxicity.

RESULTS:

Twenty-two patients (44 ears) were included in the study, with baseline and most recent audiology testing after treatment ranging from 84 days before to 496 days after treatment. Fifteen patients (30 ears) also underwent testing during treatment starting after the second infusion up until the day of, but before, the eighth infusion. Hearing loss after treatment met criteria for ototoxicity in 17 of the 44 ears (38.6%), with 11 of the 22 patients (50.0%) meeting criteria in at least 1 ear. The pure-tone average decibel hearing levels (HLs) across all 44 ears demonstrated hearing loss after treatment (P = 0.0029), specifically at high (P = 0.0008) and middle frequencies (P = 0.0042), but not at low frequencies (P = 0.8344). Patients who were older also were more likely to experience hearing loss after treatment (P = 0.0048).

CONCLUSIONS:

Audiometric data demonstrate that teprotumumab influences hearing function, most significantly at higher frequencies and in older patients. Audiometric testing is critical for counseling patients regarding teprotumumab treatment. A protocol for monitoring hearing during treatment is needed to detect and manage hearing changes associated with teprotumumab use.

FINANCIAL DISCLOSURE(S):

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

2024-01-01·Ophthalmology

Glycemic Trends in Patients with Thyroid Eye Disease Treated with Teprotumumab in 3 Clinical Trials

Article

作者: Holt, Robert J ; Wester, Sara Tullis ; Kim, Sun ; Smith, Terry J ; Hsu, Kate ; Bhattacharya, Rajib K ; Cavida, Dustin ; Barbesino, Giuseppe ; Fu, Qianhong

PURPOSE:

Assess incidence, severity, and glucose excursion outcomes in thyroid eye disease (TED) patients receiving the insulin-like growth factor-1 receptor inhibitor teprotumumab from 3 clinical trials.

DESIGN:

Analysis of pooled glycemic data over time.

PARTICIPANTS:

Eighty-four teprotumumab- and 86 placebo-treated active TED patients from the phase 2 and phase 3 (OPTIC) controlled clinical trials and 51 teprotumumab-treated patients from the OPTIC extension (OPTIC-X) trial.

METHODS:

Eight intravenous infusions were given over 21 weeks. Phase 2 serum glucose was measured at weeks 1, 4, 15, and 21, with fasting measurements at weeks 1 and 4. Serum glucose was measured at each study visit in OPTIC and OPTIC-X, with fasting measurements at weeks 1 and 4 (in patients without diabetes) or all visits (in patients with diabetes). In all studies, hemoglobin A1c (HbA1c) was measured at baseline, 12, and 24 weeks plus weeks 36 and 48 in OPTIC-X.

MAIN OUTCOME MEASURES:

Serum glucose and HbA1c.

RESULTS:

In the phase 2 and 3 studies, 9 hyperglycemic episodes occurred in 8 teprotumumab patients; mean HbA1c level increased 0.22% from baseline to week 24 (to 5.8%; range, 5.0%-7.9%) versus 0.04% in patients receiving the placebo (to 5.6%; range, 4.6%-8.1%). At study end, 78% (59/76) of teprotumumab patients and 87% (67/77) of patients receiving placebo had normoglycemic findings. Normoglycemia was maintained in 84% (57/68) of patients receiving teprotumumab and 93% (64/69) of patients receiving placebo. Among baseline prediabetic patients, 43% (3/7) remained prediabetic in both groups, and 29% (2/7) of teprotumumab patients and 14% (1/7) of patients receiving placebo had diabetic findings at week 24. OPTIC-X patients trended toward increased fasting glucose and HbA1c whether initially treated or retreated with teprotumumab. Fasting glucose commonly rose after 2 or 3 infusions and stabilized thereafter. Most hyperglycemic incidents occurred in patients with baseline prediabetes/diabetes but were controlled with medication. No evidence was found for progression or increased incidence of hyperglycemia with subsequent doses.

CONCLUSIONS:

Serious glycemic excursions are uncommon in patients with normoglycemia before teprotumumab therapy. Patients with controlled diabetes or impaired glucose tolerance can be treated safely if baseline screening, regular monitoring of glycemic control, and timely treatment of hyperglycemia are practiced.

FINANCIAL DISCLOSURE(S):

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

252

项与替妥木单抗相关的新闻（医药）

2024-04-24

·FiercePharma

Orphan drug market to reach $270B by 2028, led by J&J, Vertex and Roche: Evaluate

Several factors come into play to dull orphan drugs' shine such as the “blazing return of big drugs for big diseases,” according to Evaluate. The orphan drug sector has long been clearing growth in the larger pharmaceutical market with booming sales. But, thanks to blockbuster meds across wider disease areas and other challenges, the lucrative market may soon slow down for the first time in years. According to Evaluate’s 2024 report, “Orphan Drugs are Losing Their Sparkle,” the category is set to pick up $185 billion this year and some $270 billion by 2028. Yet, sales growth is notably shrinking. The meds averaged an almost 11% sales increase in the decade ending in 2023 but will "barely hit double digits" through 2030. Several factors come into play to dull orphan drugs' shine, such as the “blazing return of big drugs for big diseases,” according to Evaluate. While the obesity market is currently the hottest ticket, blockbusters across disease areas such as neuroscience, immunology and oncology also stand to overtake orphan drug’s slice of the pie. Plus, there are pricing pressures stemming from the high price tag on orphan drugs. Payers are “more discerning” as of late and aren’t as keen to cover the steep prices, favoring more widespread disease areas instead, according to Evaluate. Still, the sales slowdown is “relative,” head of thought leadership at Evaluate Daniel Chancellor said in a press release. “As the overall prescription drug market continues to grow, so will that for rare diseases.” 2028's top orphan drugs According to the report, the top 10 most valuable orphan drugs will together collect more than $57 billion in 2028. That top 10 list has had a bit of a shakeup since Evaluate’s last ranking in 2023, largely due to increasing competition and the Inflation Reduction Act. Johnson & Johnson’s multiple myeloma blockbuster Darzalex, Vertex’s cystic fibrosis med Trikafta and Roche’s hemophilia A therapy Hemlibra all kept their top three slots on Evaluate’s list of the 10 top sellers by 2028 in worldwide sales with predicted respective revenues of $17 billion, $8.7 billion and $6.2 billion. However, AbbVie’s popular cancer med Imbruvica has fallen out of the top 10 thanks to Beigene’s rival BTK inhibitor Brukinsa and AstraZeneca’s Calquence. While Calquence is slated for $4 billion in 2028 sales and Brukinsa should pick up $3.8 billion, AZ’s offering fell from fifth place to seventh over the past year. Argenx’s Vyvgart also slipped, dropping to 14th place with a forecast $3 billion in 2028. The generalized myasthenia gravis drug is challenged by growing competition such as UCB’s two new treatment options, Zilbrysq and Rystiggo, plus upcoming threats from Johnson & Johnson’s nipocalimab. Despite label expansions last year, Roche’s spinal muscular atrophy therapy Evrysdi had a similar story with competition from Biogen's Spinraza and Novartis' Zolgensma. Meanwhile, new entrants to the top 10 list included Incyte and Novartis’ JAK inhibitor Jakafi, which placed sixth with a 2028 sales expectation of $4.2 billion, and J&J’s Carvykti. The latter is the only CAR-T therapy to appear on the top 10 list with $4.4 billion in predicted 2028 sales. As for the wider 2028 picture, Amgen swiped AbbVie’s spot on the list of the top 10 companies with largest orphan drug sales. That can be attributed to Amgen’s $27.8 billion acquisition of rare disease drugmaker Horizon Therapeutics, which brings orphan drugs Tepezza, Krystexxa and Uplizna into the fold. The top spots in that ranking go to J&J, Roche and AZ, with J&J taking No. 1 in a landslide. The company is expected to bring in over $30 billion in 2028 orphan drug sales, while Roche at No. 2 looks to take home $16.8 billion.

并购孤儿药

2024-04-16

·药智网

全球TOP20药企狂砸研投超万亿元，都干了啥？

进入到2024年，一个行业“隐形”的共识是，大药企们越来越依靠外部引进来维系增长。根据已披露2023年财报的全球上市制药公司，以全年营收排序，计算了TOP20公司的研发费用率（研发费用/总营收*100%）。整体来看，依靠外部引进的趋势在全球TOP20制药公司中呈现分化，以再生元、福泰为代表的Biopharma、以罗氏、诺华为代表的Bigpharma，仍然以较高的研发费用率“消化”，而赛诺菲、艾伯维、安进等却将研发费用“让渡”给了外部引进。不过，诺和诺德却是TOP20中的“一枝独秀”，不断攀升的市值、高速增长的营收，产品几乎纯靠自研，研发费用率却只处于14%的“地板”水平，然而老对手礼来2023年的研发费用率，却足足比他多了一倍。如果计算TOP20公司整体的研发投入，金额超过1632亿美元（约合11800亿元），平均研发费用率约为25%。以2023年营收为统计指标；其中，罗氏、强生、默克、赛诺菲、拜耳仅计算制药和疫苗业务图片来源：E药经理人01砸钱选规模or选创新？身居“高位”集体这样回答20家跨国药企中，除了Moderna之外，拥有高研发费用率的企业与往年没什么不同，又早已大不相同。罗氏、诺华一直保持在较高的研发费用率水平，两家以自研驱动的Biopharma再生元、福泰制药也同样如此。但与此前明显不一样的是，他们的前面有了默沙东这样砸钱更猛的企业，同时，各家企业的研发策略，纷纷朝着一个新的趋势变了。当外部经济环境波动，自研投入回报率亟需拯救，临床屡屡折戟，赚钱更难，新兴生物技术的活跃很可能颠覆下一个10年时，大药企们纷纷加大了外部创新力度，调整研发策略，合理分散风险，与之伴随的是全球架构的调整。原由内部研发驱动的罗氏如此，内部研发产品在业界遥遥领先的诺华也是如此。研发费用率在30%及以上水平的企业，更是将行业的并购大趋势深刻演绎，默沙东、礼来、再生元和福泰，都纷纷颠覆了多年来鲜少并购、或研投过于保守的印象。默沙东一改10年前被诟病研投过于保守的局面，2023年整体研发费用高达300多亿美元。2022年，默沙东的研发费用率约为23%，1年时间过去，这一数字已多出1倍不止。其中，114亿美元用于并购，仅收购Prometheus高调杀入中重度炎症性肠病（IBD）领域，就花去108亿美元。不仅如此，默沙东将并购、BD之风延续到了2024年，其在年初JPM大会上就释放了“2024年大戏仍旧是并购与BD”的信号。就在近期，默沙东再次出手收购了一家ADC初创公司Abceutics。除了并购，默沙东剩下还有近200亿美元的研发投入，成为“砸钱”最狠的MNC。历史上很少作外部并购的礼来，摇身变为“并购狂”。2023年，礼来几乎每月达成一起并购交易，收购公司涉及糖尿病细胞疗法、ADC、核药等诸多领域，快速拓展至了全球诸多新兴潜力领域。一直专注于以“自研”破局的Biopharma再生元，自2022年打破35年不收购”金身“后，逐步加大了小型并购频率。今年年初，再生元收购了明星Biotech公司2seventy bio，成功获得后者在研新型免疫细胞疗法的全部开发和商业化权益。近两年的几次收购，也反映了再生元战略上出现的变化。福泰制药则打破了“补强型”小型并购的传统，横向拓展的并购动作变得多起来，同时开始转向了巨额并购。4月10日，福泰制药和Alpine Immune Sciences共同宣布，两家达成最终协议，前者将以每股65美元或49亿美元的现金、总价约49亿美元收购Alpine，押注IgA肾病领域潜在BIC药物，该笔并购系今年自免领域最大收购诞生。另一面，这几家大药企之所以将研发费用率放在一个高水平，原因还在于，当下他们既处于格外惹眼的聚光灯下，也如行走在钢索上一样，如履薄冰。默沙东一类的企业，其焦虑正刻画进行动当中。K药有可能成为史上“最短命药王”，下一步，怎么办？如何继续发挥在肺癌领域的强者优势……2024年，默沙东还会在2023年开展的20多项III期临床研究上继续加大布局，将继续为寻找超级“重磅炸弹”而筹谋。另拿礼来和福泰为例。MNC中享有市值天花板的礼来，Biopharma中冲到千亿美元市值阵营的福泰，格外受到资本市场关注。不管是已上市还是在研创新药物，两者的明星产品都被寄予了厚望。但同时，礼来和福泰所在的赛道，要么不缺强悍的竞争对手，要么因为比较“小众”，难以突破销售天花板。他们要做的，是加大研发，巩固自身的产品优势，同时开拓更为广阔的想象空间。于是2023年以来，礼来的研发之道，在于既要在GLP-1赛道上“称霸”，又要在肿瘤、中枢神经、自免等领域多点开花，还要对不同新兴技术领域的初创企业进行投资，扩展想象力。而福泰的研发之道在于，充分发挥基因编辑技术优势，夯实在罕见病药物研发上的护城河，巩固在囊性纤维化产品上的“统治级”地位。同时继续加大投入，跑在能与GLP-1市场潜力相媲美的镇痛药赛道最前列，用变革性的治疗方案持续赢得市场的青睐。02诺和诺德的“反差”其实可以看到，研发费用率TOP10的几家公司存在很大的共性——大手笔进行BD和并购，而研发费用率在第10名开外的几家公司，其实原因各异，有人因为聚焦自研，但研发领域较为单一；也有人因为过度依赖外延，自研略显疲态。礼来和诺和诺德就形成了极大反差，礼来以29%的研发费用率仅次于Moderna、再生元和福泰等三家Biopharma，而诺和诺德的研发费用率在20家公司中几乎“垫底”，仅有14%，与其不断攀升的市值、高速增长的营收形成了鲜明对比。不过，诺和诺德的研发费用率相对较低也有其独特原因：与礼来较为多元化的业务不同，诺和诺德专注在心血管/代谢领域，其“大单品”司美格鲁肽又表现出超高增速，这才造成了研发费用与收入水平的“失衡”。从营收层面来讲，诺和诺德2322.61亿丹麦克朗（约337亿美元）的营收中，超过60%都来自于司美格鲁肽系列产品的收入。而从研发层面来讲，E药经理人曾根据公开信息统计发现，诺和诺德目前较为核心的GLP-1和胰岛素产品几乎都来自于内部自研，因此也相对“节约”了很大一笔BD或是并购的投入。不过，自去年以来，诺和诺德也释放出增加外部创新的信号。先是在2023年10月，以13亿美元的价格收购了KBP Biosciences，又在今年3月以10亿欧元收购了Cardior Pharmaceuticals。这两笔收购都是在心血管领域，也可以看出诺和诺德有意通过BD或是收购的方式，将目光向糖尿病以外的慢病领域延伸。最让人意外的其实是艾伯维，营收543.18亿美元，常年稳居前五，其研发费用在2023年为76.75亿美元，占比为14%。不过，从近10年的数据中也可以看到，艾伯维的研发投入其实一直在稳步增长，自2013年成立以来，艾伯维的研发投入已由最初的28亿美元逐年攀升至2023年的76.75亿美元，累积研发投入超过500亿美元。同时，自2023年以来，自免领域的小规模“外延创新”也在成为艾伯维的主题，尤其是在进入2024年之后，2月28日，艾伯维以超7亿美元的总额，与免疫治疗公司OSE Immunotherapeutics达成合作；一个月后，艾伯维又以超2亿美元总额将一家AI制药公司收入囊中。当然，同样遗憾的还有安进，按照2023年财报披露的数字计算，其研发费用率仅为17%，而这一数字在10年前还是22%。如果看数字则更加显著，10年前，安进全年研发费用为40.8亿美元，而到了2023年，安进的研发投入却仅增长到了47.84亿美元。不过，或许这也是从生物技术公司走向Biopharma的必由之路，以技术闻名的安进其实一直保持对前沿创新的敏感度，虽然在近几年安进的创新多来自于外部，但能够吸引到他的也多是FIC、BIC类产品。以264亿美元收购罕见病制药商Horizon，其两款重磅产品治疗甲状腺眼病的Tepezza和治疗痛风的Krystexxa，皆获得了FDA授予的孤儿药认定。并且可以看到，在近几年的AACR、ASCO等会议上，KRAS抑制剂、DLL3/CD3双抗等多个备受业界关注的焦点领域，几乎都是由安进引发的热潮。不过，同样居于“尾部”的赛诺菲，却是因BD与并购驱动增长，造成研发费用与营收比例的“割裂”。2023年，赛诺菲453.64亿欧元（约483.4亿美元）的营收，其研发费用为67.28亿欧元（约71.69亿美元），研发费用率约为15%。主要原因或许与赛诺菲的“基因”有关，通过一系列并购成为了全球营收TOP10制药企业行列，其自免领域的核心单品度普利尤单抗和肿瘤领域的核心产品治疗多发性骨髓瘤的Sarclisa都来自于外部合作。声明：本文4月15日首发于《E药经理人》（ID：eyjlr2013），经授权转载，如需二次转载请联系原作者。E药经理人媒体平台致力于成为医药行业意见领袖平台，记录和观察医药重大商业事件，展现行业的复杂与冲突，提供最前沿的思想洞见。阅读原文，是昨天最受欢迎的文章哦

并购财报抗体药物偶联物疫苗

2024-04-15

·E药经理人

默沙东、礼来进前五，诺和诺德、拜耳“垫底”，全球TOP20药企狂砸研投超万亿元，都干了啥？

罗氏、诺华沉寂“让贤”，默沙东、礼来拼命砸钱，诺和诺德研投令人“大跌眼镜”。当全球TOP20大药企研发费用率进行大PK，这场头部的较量中，谁是智者？谁是赢家？撰文| 润屿 Erin编辑| Kathy进入到2024年，一个行业“隐形”的共识是，大药企们越来越依靠外部引进来维系增长。E药经理人根据已披露2023年财报的全球上市制药公司，以全年营收排序，计算了TOP20公司的研发费用率（研发费用/总营收*100%）。整体来看，依靠外部引进的趋势在全球TOP20制药公司中呈现分化，以再生元、福泰为代表的Biopharma、以罗氏、诺华为代表的Bigpharma，仍然以较高的研发费用率“消化”，而赛诺菲、艾伯维、安进等却将研发费用“让渡”给了外部引进。不过，诺和诺德却是TOP20中的“一枝独秀”，不断攀升的市值、高速增长的营收，产品几乎纯靠自研，研发费用率却只处于14%的“地板”水平，然而老对手礼来2023年的研发费用率，却足足比他多了一倍。如果计算TOP20公司整体的研发投入，金额超过1632亿美元（约合11800亿元），平均研发费用率约为25%。以2023年营收为统计指标；其中，罗氏、强生、默克、赛诺菲、拜耳仅计算制药和疫苗业务砸钱选规模or选创新？身居“高位”集体这样回答20家跨国药企中，除了Moderna之外，拥有高研发费用率的企业与往年没什么不同，又早已大不相同。罗氏、诺华一直保持在较高的研发费用率水平，两家以自研驱动的Biopharma再生元、福泰制药也同样如此。但与此前明显不一样的是，他们的前面有了默沙东这样砸钱更猛的企业，同时，各家企业的研发策略，纷纷朝着一个新的趋势变了。当外部经济环境波动，自研投入回报率亟需拯救，临床屡屡折戟，赚钱更难，新兴生物技术的活跃很可能颠覆下一个10年时，大药企们纷纷加大了外部创新力度，调整研发策略，合理分散风险，与之伴随的是全球架构的调整。原由内部研发驱动的罗氏如此，内部研发产品在业界遥遥领先的诺华也是如此。研发费用率在30%及以上水平的企业，更是将行业的并购大趋势深刻演绎，默沙东、礼来、再生元和福泰，都纷纷颠覆了多年来鲜少并购、或研投过于保守的印象。默沙东一改10年前被诟病研投过于保守的局面，2023年整体研发费用高达300多亿美元。2022年，默沙东的研发费用率约为23%，1年时间过去，这一数字已多出1倍不止。其中，114亿美元用于并购，仅收购Prometheus高调杀入中重度炎症性肠病（IBD）领域，就花去108亿美元。不仅如此，默沙东将并购、BD之风延续到了2024年，其在年初JPM大会上就释放了“2024年大戏仍旧是并购与BD”的信号。就在近期，默沙东再次出手收购了一家ADC初创公司Abceutics。除了并购，默沙东剩下还有近200亿美元的研发投入，成为“砸钱”最狠的MNC。历史上很少作外部并购的礼来，摇身变为“并购狂”。2023年，礼来几乎每月达成一起并购交易，收购公司涉及糖尿病细胞疗法、ADC、核药等诸多领域，快速拓展至了全球诸多新兴潜力领域。一直专注于以“自研”破局的Biopharma再生元，自2022年打破35年不收购”金身“后，逐步加大了小型并购频率。今年年初，再生元收购了明星Biotech公司2seventy bio，成功获得后者在研新型免疫细胞疗法的全部开发和商业化权益。近两年的几次收购，也反映了再生元战略上出现的变化。福泰制药则打破了“补强型”小型并购的传统，横向拓展的并购动作变得多起来，同时开始转向了巨额并购。4月10日，福泰制药和Alpine Immune Sciences共同宣布，两家达成最终协议，前者将以每股65美元或49亿美元的现金、总价约49亿美元收购Alpine，押注 IgA肾病领域潜在BIC药物，该笔并购系今年自免领域最大收购诞生。另一面，这几家大药企之所以将研发费用率放在一个高水平，原因还在于，当下他们既处于格外惹眼的聚光灯下，也如行走在钢索上一样，如履薄冰。默沙东一类的企业，其焦虑正刻画进行动当中。K药有可能成为史上“最短命药王”，下一步，怎么办？如何继续发挥在肺癌领域的强者优势……2024年，默沙东还会在2023年开展的20多项III期临床研究上继续加大布局，将继续为寻找超级“重磅炸弹”而筹谋。另拿礼来和福泰为例。MNC中享有市值天花板的礼来，Biopharma中冲到千亿美元市值阵营的福泰，格外受到资本市场关注。不管是已上市还是在研创新药物，两者的明星产品都被寄予了厚望。但同时，礼来和福泰所在的赛道，要么不缺强悍的竞争对手，要么因为比较“小众”，难以突破销售天花板。他们要做的，是加大研发，巩固自身的产品优势，同时开拓更为广阔的想象空间。于是2023年以来，礼来的研发之道，在于既要在GLP-1赛道上“称霸”，又要在肿瘤、中枢神经、自免等领域多点开花，还要对不同新兴技术领域的初创企业进行投资，扩展想象力。而福泰的研发之道在于，充分发挥基因编辑技术优势，夯实在罕见病药物研发上的护城河，巩固在囊性纤维化产品上的“统治级”地位。同时继续加大投入，跑在能与GLP-1市场潜力相媲美的镇痛药赛道最前列，用变革性的治疗方案持续赢得市场的青睐。推荐阅读 * AZ坐稳龙头，百济、诺华、BMS并列第7！2023全球制药创新和发明指数TOP30都有谁？* 当罗氏沉寂、AZ迸发，礼来超越强生，TOP20药企交出Big Pharma成长选规模or选创新的答案！诺和诺德的“反差”其实可以看到，研发费用率TOP10的几家公司存在很大的共性——大手笔进行BD和并购，而研发费用率在第10名开外的几家公司，其实原因各异，有人因为聚焦自研，但研发领域较为单一；也有人因为过度依赖外延，自研略显疲态。礼来和诺和诺德就形成了极大反差，礼来以29%的研发费用率仅次于Moderna、再生元和福泰等三家Biopharma，而诺和诺德的研发费用率在20家公司中几乎“垫底”，仅有14%，与其不断攀升的市值、高速增长的营收形成了鲜明对比。不过，诺和诺德的研发费用率相对较低也有其独特原因：与礼来较为多元化的业务不同，诺和诺德专注在心血管/代谢领域，其“大单品”司美格鲁肽又表现出超高增速，这才造成了研发费用与收入水平的“失衡”。从营收层面来讲，诺和诺德2322.61亿丹麦克朗（约337亿美元）的营收中，超过60%都来自于司美格鲁肽系列产品的收入。而从研发层面来讲，E药经理人曾根据公开信息统计发现，诺和诺德目前较为核心的GLP-1和胰岛素产品几乎都来自于内部自研，因此也相对“节约”了很大一笔BD或是并购的投入。不过，自去年以来，诺和诺德也释放出增加外部创新的信号。先是在2023年10月，以13亿美元的价格收购了KBP Biosciences，又在今年3月以10亿欧元收购了Cardior Pharmaceuticals。这两笔收购都是在心血管领域，也可以看出诺和诺德有意通过BD或是收购的方式，将目光向糖尿病以外的慢病领域延伸。最让人意外的其实是艾伯维，营收543.18亿美元，常年稳居前五，然而其研发费用在2023年却为76.75亿美元，占比仅为14%，排在top20药企中的末尾。艾伯维的研发费用居于“尾部”也并非仅在2023年。E药经理人曾统计2022年之前10年的全球制药TOP10药企的研发投入水平，艾伯维也是“底部”成员。不过，从近10年的数据中也可以看到，艾伯维的研发投入其实一直在稳步增长，自2013年成立以来，艾伯维的研发投入已由最初的28亿美元逐年攀升至2023年的76.75亿美元，累积研发投入超过500亿美元。同时，自2023年以来，自免领域的小规模“外延创新”也在成为艾伯维的主题，尤其是在进入2024年之后，2月28日，艾伯维以超7亿美元的总额，与免疫治疗公司OSE Immunotherapeutics达成合作；一个月后，艾伯维又以超2亿美元总额将一家AI制药公司收入囊中。当然，同样遗憾的还有安进，按照2023年财报披露的数字计算，其研发费用率仅为17%，而这一数字在10年前还是22%。如果看数字则更加显著，10年前，安进全年研发费用为40.8亿美元，而到了2023年，安进的研发投入却仅增长到了47.84亿美元。不过，或许这也是从生物技术公司走向Biopharma的必由之路，以技术闻名的安进其实一直保持对前沿创新的敏感度，虽然在近几年安进的创新多来自于外部，但能够吸引到他的也多是FIC、BIC类产品。以264亿美元收购罕见病制药商Horizon，其两款重磅产品治疗甲状腺眼病的Tepezza和治疗痛风的Krystexxa，皆获得了FDA授予的孤儿药认定。并且可以看到，在近几年的AACR、ASCO等会议上，KRAS抑制剂、DLL3/CD3双抗等多个备受业界关注的焦点领域，几乎都是由安进引发的热潮。不过，同样居于“尾部”的赛诺菲，却是因BD与并购驱动增长，造成研发费用与营收比例的“割裂”。2023年，赛诺菲453.64亿欧元（约483.4亿美元）的营收，其研发费用却仅为67.28亿欧元（约71.69亿美元），研发费用率约为15%。主要原因或许与赛诺菲的“基因”有关，通过一系列并购成为了全球营收TOP10制药企业行列，其自免领域的核心单品度普利尤单抗和肿瘤领域的核心产品治疗多发性骨髓瘤的Sarclisa都来自于外部合作。Nature杂志曾统计2015年1月1日至2021年12月31日期间，FDA批准的前20家制药公司药物来源，赛诺菲和强生是前十中唯二获批的产品全部依赖“外部创新”的公司。回复“CXO”，了解电子期刊详情精彩推荐CM10 | 集采 | 国谈 | 医保动态 | 药审 | 人才 | 薪资 | 榜单 | CAR-T | PD-1 | mRNA | 单抗 | 商业化 | 国际化｜猎药人系列专题 | 出海启思会 | 声音·责任 | 创百汇 | E药经理人理事会 | 微解药直播 | 大国新药 | 营销硬观点 | 投资人去哪儿 | 分析师看赛道 | 药事每周谈 | 医药界·E药经理人 | 中国医药手册创新100强榜单 | 恒瑞 | 中国生物制药 | 百济 | 石药 | 信达 | 君实 | 复宏汉霖｜翰森 | 康方生物 | 上海医药 | 和黄医药 | 东阳光药 | 荣昌 | 亚盛医药 | 齐鲁制药 | 康宁杰瑞 | 贝达药业 | 微芯生物 | 复星医药｜再鼎医药｜亚虹医药跨国药企50强榜单 | 辉瑞 | 艾伯维 | 诺华 | 强生 | 罗氏 | BMS | 默克 | 赛诺菲 | AZ | GSK | 武田 | 吉利德科学 | 礼来 | 安进 | 诺和诺德 | 拜耳 | 莫德纳 | BI | 晖致 | 再生元

并购财报疫苗

100 项与替妥木单抗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	替妥木单抗	L01XC	DB06343

研发状态

适应症	最高研发状态	国家/地区	公司
横纹肌肉瘤	终止	意大利更多	Hoffmann-La Roche, Inc. 更多
晚期非小细胞肺癌	终止	-	Hoffmann-La Roche, Inc. 更多
非鳞状非小细胞肺癌	终止	德国更多	Hoffmann-La Roche, Inc. 更多
滑膜肉瘤	终止	瑞典更多	Hoffmann-La Roche, Inc. 更多
难治性尤文肉瘤	终止	加拿大更多	Hoffmann-La Roche, Inc. 更多

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临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04478994 (CTgov)	临床1期	弥漫性硬皮病	3	Placebo	淵範顧範鏇窪夢淵鏇選(鑰餘衊顧蓋窪簾築鑰鹽) = 觸積觸餘遞鑰廠壓觸壓蓋襯鑰鹽齋壓積遞醖廠 (遞艱膚鏇願鬱醖淵憲鹽, 衊窪鬱齋膚鬱鬱簾簾簾 ~ 齋遞鑰窪構膚築鏇醖艱) 更多	-	2024-04-19
ARVO2023	N/A	格雷夫斯眼病	19	Teprotumumab	醖襯膚願襯鹽鹹衊範鏇(繭製範繭積選觸餘壓艱) = 廠餘廠獵餘蓋顧糧餘膚鹹範鏇糧鑰鏇繭淵醖顧 (齋築齋願蓋鏇積鹽鏇構 ) 更多	-	2023-04-23
PA059 (AAO2021)	N/A	炎症 \| 格雷夫斯眼病	-	Teprotumumab	憲構鏇襯鑰淵構齋選積(簾糧構鏇醖廠鑰壓築襯) = 觸範糧憲襯願網觸醖構築淵顧艱遞鹹鹽鏇襯憲 (網衊壓壓繭製壓壓襯觸 )	积极	2021-11-15
AAO2021	N/A	格雷夫斯眼病	51	Teprotumumab	窪積夢齋齋觸積鬱夢窪(鹹製鑰鹽簾襯廠齋製廠) = 40% 蓋網壓獵憲壓憲遞築鹽 (鏇構衊憲廠積觸顧築膚 ) 更多	-	2021-11-13
NCT03461211 (CTgov)	临床3期	格雷夫斯眼病	51	Placebo+Teprotumumab (Teprotumumab (OPTIC Placebo))	憲窪壓獵膚構構淵衊遞(遞壓窪積壓選獵壓襯夢) = 艱衊鑰願鑰鏇蓋鬱鑰觸壓鑰構齋繭餘膚膚觸餘 (願網願簾範積網餘選襯, 艱願夢夢鏇憲獵顧構構 ~ 壓簾鏇願糧醖餘鹹鑰鹹) 更多	-	2021-07-19
NCT03461211 (CTgov)	临床3期	格雷夫斯眼病	51	Teprotumumab (Teprotumumab (OPTIC Teprotumumab))	憲窪壓獵膚構構淵衊遞(遞壓窪積壓選獵壓襯夢) = 顧鹽簾範憲範鑰範醖顧壓鑰構齋繭餘膚膚觸餘 (願網願簾範積網餘選襯, 夢醖夢鑰醖築糧獵艱獵 ~ 窪壓窪繭獵襯憲鏇獵鹹) 更多	-	2021-07-19
2021 ARVO Annual Meeting (ARVO2021)	N/A	格雷夫斯眼病	12	Teprotumumab	獵網糧鹹範鏇窪鬱鏇襯(觸憲願夢襯鑰衊鏇獵淵) = 構窪蓋襯壓築觸襯製網範壓廠觸鑰膚願壓遞願 (鹹醖選範構壓憲鬱襯齋, [-4.5 ~ -1.1])	积极	2021-06-01
NCT04040894 (ARVO2021)	N/A	格雷夫斯眼病	13	Teprotumumab	糧齋獵網餘窪積膚簾積(糧願繭遞構夢簾憲壓願) = 醖醖襯襯築齋顧網製憲觸膚蓋獵蓋鑰壓願齋齋 (憲鹽齋齋鹹觸廠窪蓋艱 ) 更多	-	2021-06-01
ARVO2021	N/A	-	22	Teprotumumab	糧繭鑰鏇夢廠糧築餘襯(構構鏇簾願餘窪窪鬱願) = 積鑰膚繭選淵積襯製鏇廠齋鹽窪淵艱糧醖積獵 (壓艱淵衊網構餘壓選廠 ) 更多	-	2021-06-01
NCT00760929 (CTgov)	临床2期	非鳞状非小细胞肺癌 \| 晚期非小细胞肺癌	171	erlotinib [Tarceva]+RG1507 (R1507 (9mg/kg iv))	鏇繭艱鏇簾網鬱膚遞鹽(淵製簾願鹹膚鬱淵願鬱) = 簾廠簾遞鬱範廠網壓鹽網廠鏇鹽選構鹹艱鑰窪 (膚鏇遞鹽選蓋膚膚淵衊, 簾觸製膚鑰積鏇顧構繭 ~ 積顧膚積獵壓築簾餘築) 更多	-	2021-01-05
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