Adalimumab-ATTO(Amgen)

以下分析仅从专利角度观察，不替代市场、产品、财务和组织判断，也不构成投资建议；它提供的是新闻、融资和财报之外的一个补充视角。 2023年1月31日，Amgen的阿达木单抗生物类似药Amjevita正式获得许可进入美国市场。 表面上看，这是Humira专利悬崖真正到来的一天。Humira的美国核心物质专利早在2016年12月便已到期，Amgen的产品也已经提前多年获得监管批准，但直到核心专利到期六年多以后，生物类似药才真正进入美国市场。 然而，当Amgen终于推开Humira市场的大门时，门后的世界已经发生了变化。 2022年，Humira全球销售收入达到212.37亿美元；到2025年，这一数字下降至45.40亿美元。与此同时，AbbVie的两款新型免疫药物Skyrizi和Rinvoq在2025年分别实现175.62亿美元和83.04亿美元收入，合计达到258.66亿美元，已经超过Humira历史上的销售高峰。 这不是一次普通的新老产品替代。 AbbVie先利用Humira的多层专利组合，把生物类似药进入美国市场的时间推迟；再利用由此获得的时间、现金流、医生资源和临床网络，引进Skyrizi、开发Rinvoq，并让两款不同机制的新药共同承接Humira留下的免疫疾病市场。 因此，Humira案例真正值得研究的，并不是一家药企申请了100多件专利，而是：一家药企如何把专利权转化为市场时间，再把市场时间转化为下一代产品。 Humira的核心专利到期，并没有立即带来市场开放 （图源于网络） Humira即阿达木单抗，是一种针对TNF-α的单克隆抗体，长期用于类风湿关节炎、银屑病关节炎、强直性脊柱炎、斑块型银屑病、克罗恩病、溃疡性结肠炎等多种免疫炎症性疾病。 它并不是只在一个疾病市场中销售，而是横跨风湿科、皮肤科和消化科，逐渐发展成一个庞大的免疫治疗平台。 AbbVie在2016年年报中明确披露，覆盖阿达木单抗的美国物质专利于2016年12月到期，但同时强调，其非物质专利最早要到2022年以后才陆续到期。 所谓物质专利，主要保护药物本身。对于普通观察者而言，核心药物专利到期似乎意味着竞争者可以立即进入。 但是，医药产品并不是取得一种活性成分以后便能直接上市。尤其是生物药，竞争者还需要完成： 细胞培养和抗体表达；产品纯化与杂质控制；制剂稳定性设计；质量属性控制；不同适应症的临床和标签设计；给药剂量及给药方案；监管申报和商业化生产。 AbbVie围绕这些环节持续申请了大量后续专利。到2016年起诉Amgen时，AbbVie在诉状中称自己已经取得100多件Humira相关专利，认为Amgen拟上市产品可能涉及其中至少61件；但依据BPCIA的第一轮诉讼规则，当时实际进入诉讼的只有10件。 这10件专利并不包括已经到期的核心阿达木单抗物质专利，而主要分布在： 抗体制造与细胞培养；抗体纯化和产品质量；稳定液体制剂；特定疾病用途；特定剂量和给药方案。 其中，制造、纯化和质量控制专利占据了相当大的比例。 这说明AbbVie的专利策略已经从“保护阿达木单抗是什么”，转向“控制阿达木单抗如何被制造、配制、批准和使用”。 后来，美国第七巡回上诉法院在审理Humira专利和解相关反垄断案件时，使用了132件专利这一口径，并指出其中许多专利的期限延续到2023年以后。 不同文件中出现的100多件、61件、10件和132件，并不是相互矛盾： 100多件是AbbVie当时所称的整体Humira专利资产；61件是AbbVie在与Amgen进行信息交换后认为可能被涉及的专利；10件是BPCIA程序下进入第一轮诉讼的专利；132件是后来法院描述整个相关专利组合时采用的统计口径。 真正重要的不是哪个数字最准确，而是这些专利覆盖了竞争者进入市场所要经过的多个环节。 为什么美国要为生物类似药设计一套BPCIA制度？ （图源于网络） 理解AbbVie与Amgen的诉讼，首先需要理解美国的BPCIA制度。 BPCIA即《生物制品价格竞争与创新法案》。它建立了生物类似药的简化上市路径，同时设计了一套在生物类似药上市前解决专利争议的机制。 其基本出发点是：生物药与普通小分子药不同。 小分子药通常具有相对明确的化学结构，仿制药企业可以通过证明活性成分相同、生物等效等方式申请上市。 生物药则由活细胞生产。细胞株、培养条件、纯化方法和生产控制稍有差异，最终产品的糖基化、聚集体、杂质和生物活性都可能发生变化。因此，生物类似药通常不是原研生物药的分子级完全复制品，而是需要证明与参照药“高度相似”，并且在安全性、纯度和效力方面不存在有临床意义的差异。 BPCIA一方面为生物类似药建立351(k)简化申请路径，另一方面给予原研生物药通常所说的“4年＋12年”监管独占： 原研生物药首次获得许可后4年内，生物类似药申请原则上不能提交；首次许可后12年内，FDA原则上不能使生物类似药批准生效。 这12年是监管独占，并不是专利期限。监管独占届满后，生物类似药是否能够进入市场，还要看相关专利是否到期、是否被无效、是否不构成侵权，以及双方是否达成许可和解。 BPCIA的“专利舞蹈” BPCIA最有特色的制度，被称为“专利舞蹈”。 FDA受理生物类似药申请后，申请人可以按照法定程序向原研企业提供申请文件和制造工艺资料。原研企业据此列出其认为可能被侵犯的专利，生物类似药企业再逐项提出不侵权、无效或者等待专利到期的理由。 双方随后协商哪些专利先进入诉讼。 如果不能达成一致，生物类似药申请人可以在相当程度上影响第一轮诉讼的专利数量。进入第一轮的专利会先行诉讼，剩余专利则可能在申请人发出商业上市通知后，进入第二轮诉讼或者临时禁令程序。 这套程序可以概括为： FDA受理申请 → 交换申请和制造资料 → 原研企业列出相关专利 → 生物类似药企业逐项回应 → 双方选择首轮诉讼专利 → 第一轮诉讼 → 商业上市通知 → 剩余专利诉讼、禁令或者和解。 美国最高法院在2017年的Sandoz v. Amgen案中进一步明确，原研企业不能依据联邦BPCIA直接取得禁令，强迫生物类似药申请人交出申请和制造资料；但申请人拒绝参与，也会产生相应程序后果，原研企业可以立即提起确认之诉。同时，180日商业上市通知可以在FDA正式批准以前发出，不必等到批准以后重新计算。 因此，所谓“专利舞蹈”既不是完全强制，也不是毫无代价的自愿程序。它的本质是：把生物类似药上市前原本模糊的专利风险，提前转化成可以交换、诉讼和谈判的问题。 对于原研企业，BPCIA使其有机会接触生物类似药的制造资料，并据此判断制造、纯化和质量专利是否可能被侵犯。 对于生物类似药企业，BPCIA则提供了一条在实际上市以前清理专利障碍、获得确定上市时间的路径。 AbbVie与Amgen为什么最终只打了10件专利？ （图源于网络） Amgen为其阿达木单抗生物类似药提交申请后，双方按照BPCIA启动专利信息交换。 AbbVie声称，其根据Amgen提供的申请和制造资料，认为拟上市产品可能涉及至少61件Humira相关专利。但双方并没有把61件专利同时送入法院。 根据BPCIA的选择机制，Amgen确定首轮各方选择6件专利。AbbVie和Amgen分别提交自己的选择，由于其中有2件重合，最后形成10件第一轮诉讼专利。 从这些专利的结构看，AbbVie真正试图控制的并不是一个抽象的“阿达木单抗”，而是Amgen进入市场的完整路径： 其中有些专利由AbbVie主动选择，有些则由Amgen主动选入第一轮诉讼。 Amgen为什么把某些专利主动放进诉讼，公开文件没有给出完整解释。通常而言，生物类似药企业可能希望优先解决自己认为较弱、较容易规避，或者最可能阻碍产品上市的专利。 不过，这场诉讼没有走到实体判决。法院最终没有判断： 10件专利是否全部有效；Amgen是否实际侵犯这些专利；61件专利中究竟哪些真正难以绕开；AbbVie能否凭借其中任何一件专利将Amgen阻挡至更晚时间。 2017年9月，双方达成全球和解。AbbVie向Amgen提供非独占专利许可，允许Amgen自2018年10月16日起在欧洲多数国家进入，自2023年1月31日起在美国进入；Amgen则按照协议支付许可费，具体商业条款保密。 因此，AbbVie并没有获得一份“61件专利全部有效、Amgen全部侵权”的胜诉判决。 它获得的是另一种经营结果：把原本充满不确定性的专利争议，转化成一个确定的美国市场进入日期。 Amgen也并非一无所获。它获得了： 明确的上市日期；非独占专利许可；提前安排生产和销售的确定性；避免继续面对几十件专利诉讼的机会。 双方交换的，本质上是：AbbVie用进入许可换取市场时间，Amgen用许可费和延迟上市换取进入确定性。 专利高墙没有消灭悬崖，而是把悬崖推迟 Humira专利组合的价值，不应被理解为让生物类似药永远无法进入。 美国法院后来明确指出，很多Humira专利的期限延续到2023年以后，但AbbVie接受竞争者从2023年开始进入，换取对方承诺在此以前不上市。 这意味着AbbVie没有坚持把每一件专利的期限全部打到底，而是主动进行了折中。 从2017年达成第一项和解，到2023年美国生物类似药集中上市，AbbVie获得了大约五年多的确定性窗口；如果从2016年核心物质专利到期计算，则实际延后了六年多。 在这段时间里，Humira继续创造巨额现金流。2022年，即美国生物类似药正式进入前一年，Humira全球收入仍然达到212.37亿美元，占AbbVie总收入约37%。 仅仅推迟竞争，并不能从根本上解决专利悬崖。 如果AbbVie只是多卖几年Humira，却没有培育下一代产品，那么2023年以后依然会出现巨大的收入断层。 专利高墙真正产生长期价值的前提是：企业知道怎样使用专利换来的时间。 AbbVie在Humira高墙仍然有效时，开始寻找接班人 2016年是AbbVie整个产品接力中的关键年份。 这一年，Humira美国核心物质专利到期；同年3月，AbbVie与勃林格殷格翰达成合作，引进当时仍处于银屑病三期临床阶段的抗IL-23抗体BI 655066，也就是后来的Skyrizi。AbbVie支付5.95亿美元首付款，并取得后续全球开发和商业化主导权。 这不是等Humira销售下降以后再寻找替代产品，而是在核心专利到期、后续专利仍能维持市场时间的时候，提前购买一项可能接班的晚期资产。 （图源于网络） Rinvoq则走的是另一条路线。 Rinvoq即upadacitinib，是AbbVie内部开发的口服JAK抑制剂。Skyrizi和Rinvoq均于2019年开始商业化：Skyrizi首先获批用于斑块型银屑病，Rinvoq首先获批用于类风湿关节炎。2019年，两款产品的全球收入分别只有3.55亿美元和4700万美元。 当时Humira仍然是绝对主力，但产品接力已经正式启动。 三款药不同，但服务的是高度重叠的市场 Humira、Skyrizi和Rinvoq并不是同一种药。 Humira是抗TNF-α抗体；Skyrizi是针对IL-23 p19亚基的单克隆抗体；Rinvoq是口服JAK抑制剂。它们的作用机制、给药方式和风险收益结构都不同。 但从企业经营角度看，它们服务的是高度重叠的免疫炎症需求，覆盖大量相同或者相近的疾病市场。 Humira市场横跨：风湿科、皮肤科、消化科。Skyrizi主要覆盖：斑块型银屑病、银屑病关节炎、克罗恩病和溃疡性结肠炎；Rinvoq则覆盖：类风湿关节炎、银屑病关节炎、强直性脊柱炎、特应性皮炎、克罗恩病和溃疡性结肠炎等疾病。 这意味着AbbVie可以大量复用Humira时代已经形成的资源： 风湿科、皮肤科和消化科医生网络；临床试验中心和研究者资源；学术推广和医学教育体系；保险公司、PBM和支付方准入经验；专科药房和患者支持体系；AbbVie在免疫领域的品牌认知。 所以，Skyrizi和Rinvoq不是从零开始进入两个新市场，而是加载在Humira已经建立的免疫商业基础设施之上。 AbbVie也没有试图寻找一款完全复制Humira的“新Humira”。 Humira覆盖的疾病和患者类型过于广泛，单一产品很难完整承接。Skyrizi是一款注射型生物药，主要在银屑病、银屑病关节炎和炎症性肠病中发挥作用；Rinvoq则是口服小分子，可以进入风湿、皮肤和消化等更广泛领域。 两款药分别承担不同角色，共同重构Humira原来的市场： Skyrizi承担精准生物药和IL-23市场； Rinvoq承担口服小分子和更广泛的免疫疾病市场。 这是一种“双产品接力”，而不是单品替代。 专利换来的时间，最终变成了收入接力 三款药的收入变化（亿美元），最能说明AbbVie产品接力的结果。 2019年，Skyrizi和Rinvoq刚刚上市时，两款产品合计收入只有4.02亿美元。2022年，Humira达到212.37亿美元销售高峰时，两款接班产品合计已经达到76.87亿美元。到2025年，Humira受到美国生物类似药竞争影响，收入下降至45.40亿美元；但Skyrizi和Rinvoq合计达到258.66亿美元，两款产品已经完全覆盖并超过Humira下降留下的缺口。2025年，Skyrizi和Rinvoq合计占AbbVie总收入约42%。AbbVie全年收入达到611.60亿美元，并在美国Humira失去独占后的第二个完整年度，超过了公司此前的收入高峰。 这说明AbbVie并没有成功阻止Humira悬崖。它完成的是另一件更重要的事：在悬崖到来以前，让新的利润来源成长到足以跨越悬崖。 Skyrizi和Rinvoq正在建立新一轮专利保护 Skyrizi和Rinvoq虽然共同承接Humira市场，但由于药物类型不同，其专利保护和竞争制度也不同。 Skyrizi走的是BPCIA生物药路径 Skyrizi是一种单克隆抗体，未来的竞争者将主要通过BPCIA的351(k)路径申请生物类似药。 AbbVie在2025年年报中披露，覆盖risankizumab的美国物质专利预计于2033年到期。 这意味着Skyrizi目前仍处于核心抗体专利直接控制产品的阶段，与2016年以后主要依靠后续专利防守的Humira并不相同。 与此同时，AbbVie已经通过适应症扩展和产品迭代，把Skyrizi从最初的银屑病药物扩展到银屑病关节炎、克罗恩病和溃疡性结肠炎，并形成皮下注射、静脉诱导、不同维持剂量和贴身注射装置等产品形态。 这些产品变化通常会带来新的制剂、剂量、用途和装置专利机会。 Skyrizi未来真正的专利考验，将发生在生物类似药申请出现以后。届时，BPCIA会迫使AbbVie把相关抗体、制剂、剂量、用途、制造和给药专利系统地摆上谈判桌。 Humira的经验意味着，2033年核心抗体专利到期，不一定等于2033年生物类似药能够立即进入。 但Skyrizi能否再现Humira的延迟效果，还要取决于： 后续专利的质量；生物类似药的实际工艺；BPCIA诉讼结果；双方是否达成许可和解；美国对药品专利高墙的政策环境。 Rinvoq走的是Hatch-Waxman小分子药路径 Rinvoq是小分子药，不适用BPCIA，而适用美国针对小分子仿制药的Hatch-Waxman制度。 在这一制度下，原研企业把符合条件的药品专利登记到FDA的Orange Book中。仿制药企业提交ANDA简化申请时，需要对相关专利作出声明。 最具竞争性的声明是Paragraph IV声明，即仿制药企业主张： 相关专利无效；专利不可执行；或者拟上市产品不构成侵权。 作出Paragraph IV声明的仿制药企业必须通知原研企业和专利权人。如果专利权人收到通知后45日内起诉，FDA对仿制药最终批准通常会被推迟30个月，除非法院更早认定专利无效或者不侵权。首个符合条件的挑战者，还可能获得180日仿制药市场独占。 因此，Hatch-Waxman把仿制药申请本身设计成一种法定的拟制侵权，使专利争议能够在产品真正上市以前解决。 它与BPCIA的共同点是：都把专利诉讼前移到竞争产品上市以前。 不同点则在于： FDA在一份2025年Rinvoq仿制药暂时批准函中列出了Orange Book中登记的数十件相关专利，涵盖不同到期时间。暂时批准意味着FDA在药学审评层面原则上认可仿制药申请，但由于专利、独占期或者诉讼障碍，产品暂时不能正式上市。 AbbVie披露，覆盖upadacitinib的美国物质专利预计于2033年到期。但在2025年9月，AbbVie已经与所有提交Rinvoq片剂ANDA的仿制药企业达成诉讼和许可和解。在取得预期儿童独占期的情况下，Rinvoq片剂预计不会在2037年4月以前面临美国仿制药进入。 换句话说，AbbVie已经再次完成了熟悉的转换： 2033年核心专利到期 → 数十件后续专利与Paragraph IV挑战 → 专利诉讼 → 许可和解 → 2037年相对确定的仿制药进入时间。 制度从Humira的BPCIA变成了Rinvoq的Hatch-Waxman，但经营逻辑没有改变。 Skyrizi和Rinvoq接力，对Amgen意味着什么？ 从法律上看，Skyrizi和Rinvoq的成长并不会影响Amgen依据和解协议销售Amjevita的权利。 Amgen仍然在2023年1月31日按约进入美国市场。 但从商业上看，Amgen得到的市场已经与2016年不同。 它原本希望进入的是一个年销售额超过200亿美元、由Humira主导的免疫疾病市场。但在Amgen等待上市的六年间，AbbVie已经推动市场发生两种变化。 Humira内部的生物类似药竞争。Amgen不是唯一进入者。多家阿达木单抗生物类似药企业在2023年陆续进入美国市场，相互争夺保险目录、PBM准入、渠道和价格空间。免疫市场向新机制药物分流。在银屑病关节炎、克罗恩病和溃疡性结肠炎等领域，医生不再只是在Humira与其生物类似药之间选择，还可以选择Skyrizi、Rinvoq以及其他新机制药物。 所以，Amgen虽然获得了进入Humira市场的钥匙，但AbbVie已经将相当一部分新增患者、医生关注和利润增长迁移到了新的产品组合。 Amgen进入的是一个正在被价格竞争分割的阿达木单抗市场，AbbVie经营的则已经是一个由多个作用机制、多个产品和多个治疗阶段共同组成的免疫平台。 这就是产品接力对竞争者产生的真正影响：竞争者终于攻进了旧产品，原研企业却已经把未来价值转移到了新产品。 AbbVie案例揭示的，不只是“专利高墙” Humira经常被作为药品专利高墙或者专利丛林的典型案例。 这种评价有其合理性。大量后续专利确实提高了竞争者的清除成本，也引发了药价、竞争和专利制度边界方面的长期争议。 但如果只把AbbVie的成功归结为“申请了很多专利”，仍然低估了这个案例。它至少包含四个相互衔接的经营动作。 核心专利创造市场：早期阿达木单抗核心专利保护药物本身，使Humira能够建立市场、适应症和商业体系。 后续专利购买时间：制造、纯化、制剂、用途和剂量专利没有永久阻止生物类似药，却显著增加了竞争者的诉讼风险和上市不确定性。 和解把不确定权利变成确定日期：AbbVie没有逐件打完全部专利，而是通过许可和解，把复杂的专利组合转化成明确的市场进入时间表。 企业用时间培育下一轮产品：AbbVie利用Humira继续创造的现金流和商业资源，引进Skyrizi、开发Rinvoq，在专利悬崖到来以前完成产品上市，并逐步将市场迁移到新的药物组合。 这四个动作连起来，才是AbbVie真正的专利经营体系： 核心专利建立市场 → 专利组合延迟竞争 → 诉讼和解确定时间 → 新产品完成利润接力 → 新产品再建立下一轮专利组合。 专利真正撬动的，是时间而不只是赔偿 在制造业专利纠纷中，人们通常关注禁令、赔偿和市场份额。 医药专利最独特的杠杆之一，则是时间。 对于一款年收入超过200亿美元的药物，竞争者晚一年进入所产生的经济价值，可能远远超过一场普通专利诉讼的赔偿额。 因此，评价Humira专利组合，不能只问： 每件专利是否足够宽；是否都能被法院维持有效；是否每件专利都能独立挡住竞争者。 还要问： 整个组合是否提高了竞争者进入的不确定性；是否形成了许可谈判筹码；是否换取了确定的市场时间；企业是否用这段时间完成了产品接力。 从这个角度看，Humira专利高墙并不等于132件“超级专利”。 其中一些专利可能容易规避，一些可能面临无效风险，一些只能覆盖特定用途、工艺或产品形态。 但当这些专利被组合起来，并嵌入BPCIA诉讼、监管审批和商业许可体系后，它们共同完成了一项非常重要的经营任务：为AbbVie购买了足以培养下一代产品的时间。 对中国药企和IPR的启示 AbbVie案例不是告诉中国药企简单模仿Humira，多申请几十件外围专利。 真正值得学习的是研发、专利、注册、临床、BD和产品经营之间的协同。 药企的专利布局不能停留在“围绕现有成果申请什么”，而应当同时回答： 核心物质专利什么时候到期？竞争者最可能从哪里进入？哪些制剂、剂量、用途和工艺真正具有临床与注册价值？哪些专利能够进入未来的诉讼和许可谈判？专利组合能够为企业争取多少时间？企业准备在这段时间内培育什么接班产品？新产品能否复用原产品的医生、临床和市场资源？下一轮专利资产是否已经提前构建？ 专利高墙如果脱离产品接力，只能延缓衰退。 产品接力如果没有专利保护，又难以获得足够长的价值兑现周期。 二者必须放在同一张经营时间表上。 结 语 Humira的核心专利终究到期了，生物类似药也终究进入了美国市场。AbbVie没有永远守住Humira。 但它通过多层专利组合和BPCIA诉讼，把原本可能更早发生的市场竞争推迟到2023年；再利用这段时间，把Skyrizi和Rinvoq推向市场，并让两款产品在Humira收入快速下降时完成接力。 与此同时，AbbVie已经开始为下一轮悬崖做准备：Skyrizi的核心抗体专利预计于2033年到期，Rinvoq的核心物质专利同样指向2033年前后；但Rinvoq已经通过后续专利、Hatch-Waxman诉讼和许可和解，将美国仿制药进入时间预期确定至2037年4月以后。 所以，AbbVie最值得研究的能力，不是拥有多少件专利，而是形成了一套可重复运行的经营机制：用专利建立排他，用制度放大排他，用诉讼兑现排他，用排他换取时间，再用时间培育下一轮增长。 Humira并没有被Skyrizi或者Rinvoq简单替代。 它完成了更重要的使命：用自己最后的专利生命和现金流，为AbbVie孵化出了下一代免疫业务。 这才是专利作为利润杠杆，在医药产业中最完整的一次展示。 （注：部分内容由AI辅助整理）

The tables have turned for the U.S. biosimilars market. With more than a decade since the first FDA biosim approval, strong launches to biologic copies to AbbVie’s Humira, J&J’s Stelara and Regeneron/Bayer’s Eylea are shifting a narrative once focused on lagging uptake of the category in The States. And although the so-called biosimilar ‘void’ —or the dearth of in-development products for the many branded drugs facing U.S. patent losses in the late 2020s and early 2030s—could pose challenges to upcoming biosimilar availability, the opportunity it presents is immense for developers willing to strike early and strike fast. “We’ve been seeing the evolution, certainly since Humira went biosimilar a few years ago,” Lisa Graver, the recently installed CEO of Iceland’s Alvotech, said of the U.S. biosim scene in a recent interview with Fierce. “We’re starting to see a different uptake pattern.” But even as regulatory and physician receptivity to the category improves, issues pertaining to reimbursement and the complex intellectual property entanglements that biosimilar developers must wade through continue to pose hurdles, Graver and other industry stakeholders said in series of recent conversations on the state of the field. While acknowledging biosimilar launches can be “somewhat product dependent,” especially with regard to reimbursement, Graver pointed to the launch of biosimilars to J&J’s immunology star Stelara (ustekinumab) early last year as a sign that use of the medicines is trending upward in the U.S. “The rate of uptake and adoption is much quicker,” she said. Industry watchers have been confounded in recent years by the uneven look of the U.S. biosimilar market, which many had originally expected to take a similar trajectory to small molecule generic drugs. But that market model has apparently been a clumsy comparator, and biosimilar adoption in the U.S. has been much more variable across different therapeutic areas, experts told Fierce in a separate feature on the biosimilar industry earlier this year. Ming Li, president of commercial operations at recent biosimilar upstart Neion Bio, echoed Graver’s enthusiasm about the uptake of biosims to Humira, Stelara and Eylea, noting that the field can’t be painted with a broad brush. Still, work remains to make the category the preferred option when prescriptions are being written, he said, calling that the “fundamental principle” that should guide legislators and regulators when drafting and implementing future policies to bolster U.S. biosimilar adoption. Prior to his role at Neion, Li had served as chief strategy officer at Alvotech. Reimbursement, meanwhile, also remains an area in need of improvement, in Graver’s estimation. “But I’m optimistic, just seeing how it’s playing out,” she said, predicting that the recent momentum in the U.S. biosimilar field is “going to continue as we see solid players in the market.” Apart from Neion and Alvotech, plus its frequent partner Teva, major outfits like Novartis spinout Sandoz, Amgen and Pfizer comprise a large chunk of the U.S. biosimilars presence. Graver, for her part, took the reins at Reykjavik-headquartered Alvotech around the end of 2026’s first quarter, replacing founder Róbert Wessman, who had steered the company as CEO since 2023. Under a strategic pact penned back in 2020, Alvotech and generics juggernaut Teva Pharmaceutical are attacking the U.S. biosimilar market together, wedding Alvotech’s manufacturing capabilities with Teva’s market know-how. Alvotech’s marketed biosimilars in the U.S. include its versions of Johnson & Johnson’s Stelara (ustekinumab) and AbbVie’s Humira (adalimumab), which helped the company generate (PDF) overall product revenue of 276.4 million in 2025, up slightly from the $273.5 million it brought home for 2024. In spite of positive changes on the legislative, regulatory and awareness fronts, the patent office remains a hotly contested battleground for biosimilar developers in the U.S. To get their biosimilars in the door, companies that look to make cheaper versions of blockbuster biologics first have to navigate waves of patents asserted by branded durgmakers. Such patent litigation often ends in a settlement that tees up the biosimilar maker to launch their offering, but typically on a delayed timeline, Tahir Amin, an intellectual property lawyer who co-founded and serves as CEO of the Initiative for Medicines, Access & Knowledge (I-MAK), explained in an interview. With the now-infamous defense AbbVie erected around its top-selling immunology drug Humira, over 200 patents effectively prevented any copies from hitting the market for seven years after its core patent expired in 2016. In those seven years before Amgen’s biosimilar Amjevita first hit the market in 2023, AbbVie earned billions in Humira-specific revenue, suggesting that stocking up on patents “obviously pays off” for original drugmakers, Amin said. The U.S. patent system, as Amin sees it, is currently a “business tool” that blocks competition. The solution, he says, is a stricter standard for patents granted through the U.S. Patent and Trademark Office (USPTO). “That's really impacting the biosimilars market, because it's costing them so much to get into the marketplace and they're often deterred, or they're going to start making choices where they're saying it's not worth our while, and that's not going to be a benefit to the U.S. consumer,” he said. For its part, Alvotech is adopting a two-pronged strategy under Graver, which directly confronts the litigation-heavy reality of the biosimilar business. “We look across the board at things that one: we know we can develop successfully,” she said, “and two: where we’re likely to be first—or at least if not the first, in the first wave to enter.” Equally important to Alvotech’s strategy are products where the company can navigate the “follow-on patents” that often accompany branded biologics, with Graver admitting that the company will “take a look at where we have the opportunity to challenge the validity of a patent.” That IP strategy is “equal in importance when we talk about our development beyond the science,” the CEO said. One ongoing patent battleground Amin pointed to, meanwhile, is Merck’s Keytruda. The deeply entrenched oncology drug’s original key U.S. patents are expected to expire in 2028, leaving a growing pipeline of Keytruda biosimilars in development in anticipation of a “patent cliff” that year. 2028 biosimilar entry for Keytruda, however, is “wishful thinking,” Amin explained in written testimony (PDF) for a drug pricing hearing before the U.S Senate Committee on Health, Education, Labor and Pensions (HELP) committee back in 2024. In fact, the notion of a ‘patent cliff’ in general is a “myth,” he said in his recent interview with Fierce, given “the way companies actually play the patent game.” In Merck’s case, the 2025 approval of its subcutaneous Keytruda Qlex stands to help the company prevent biosimilars for years beyond its initial patent expiry, for one. “The fundamental problem with biosimilar competition is I think the patent system,” Amin said. “I think we would do well to start with the patent system.” It’s a starting point that hasn’t gone unnoticed by U.S. legislators. Along with voting unanimously to advance the Biosimilar Red Tape Elimination Act, the HELP committee on June 17 agreed in a 16-6 vote to advance the Medication Affordability and Patient Integrity Act, which targets (PDF) pharmaceutical patent abuse and anticompetitive patents at the patent office. The bill aims to end the practice of drugmakers extending their product exclusivity period by submitting partial patent information in order to facilitate subsequent patents later on, U.S. Senators Maggie Hassan (D-NH) and Josh Hawley (R-MO) explained when they introduced the bill last year. If passed, companies would be required to “certify” that they have not made “inconsistent statements” to the patent office and the FDA. To put it a different way, companies can currently omit key technical information at the patent office until seeking to enforce additional secondary patents on different features of the drug years later. “Big Pharma companies have been driving up their profits by gatekeeping select drug information and exploiting our bloated bureaucracy,” Hawley said in a statement at the time. “This bipartisan legislation would require manufacturers to disclose critical drug information across agencies, so Congress can finally begin to upend Big Pharma’s anticompetitive practices.” The Senate HELP committee’s action was applauded by advocacy groups such as the Association for Affordable Medicine (AAM), which has long supported the bill. “Greater consistency and transparency between the FDA and USPTO offers stakeholders increased certainty—and that leads to a more resilient supply chain, not only better supporting patients, but also better supporting the entire healthcare system,” AAM CEO John Murphy III commented in a recent press release from the organization. Meanwhile, the Biosimilar Red Tape Elimination Act specifically looks to remove the currently imposed distinction between biosimilars and “interchangeable” biosimilars. “Working to modernize the biosimilar approval framework by eliminating outdated and unnecessary statutory requirements related to interchangeability is imperative to patient access and affordable care,” Alex Keeton, executive director for the Biosimilars Council, said in the AAM release. Biosimilar products that earn an interchangeability designation from the FDA can be freely swapped out for the pricier reference drug at the pharmacy counter, without needing the explicit go-ahead from the prescribing practitioner. In practice, that makes the process for doling out biosimilar drugs as simple as it is for small molecule generics, enabling patients and pharmacists to drive the decision. The issue, however, is that all marketed biosimilars are, by nature, interchangeable from their reference products in clinical effect. Europe, for one, has eliminated this distinction by deeming all approved biosimilar products interchangeable. That is because, in order to win approval, the medicines must have already demonstrated that they’re “comparable to their reference products” in terms of “efficacy, safety and immunogenicity,” European Medicines Agency (EMA)’s executive director Emer Cooke said in a 2022 statement. Neion Bio’s Li acknowledged the importance of “incentives” for biosimilar developers, such as the interchangeability designation, though he agreed that policymakers need to move beyond that perk, which he admitted had “proved not to be the carrot everyone was hoping for.” Time-limited market exclusivity, on the other hand, of the sort that is enjoyed by generics developers who win early approvals for their products, might better tempt companies to the biosimilar market, he reckoned. U.S. lawmakers, when crafting the biosimilar framework in the early 2000s, opted not to outright address interchangeability in the same way that Europe has, in part, because the substitutable designation wasn’t as big of an issue at the time. That’s because most biosimilars, given their biologic make-up, are administered directly by healthcare providers as opposed to being picked up by patients at the pharmacy counter, Gillian Woollett, VP, head of U.S. regulatory strategy and policy at Samsung Bioepis, explained in an interview. The challenge, Woollett said, became “misinformation” that suggested that a biosimilar without the interchangeability tag may not be the same as the reference medicine. In a potential bright spot on that front, Alvotech’s Graver noted that she believes receptiveness among U.S. physicians has “moved well in the direction of accepting biosims as true alternatives.” The Alvotech CEO added that the advent of Humira biosimilars has gone a long way to ease initial concerns about the category, too. The value and function of the interchangeability tag is a concern shared by the FDA as well. The agency has proposed guidance that would categorize all approved biosimilars as interchangeable and cut down on unnecessary testing requirements, with former FDA Commissioner Marty Makary, M.D., previously calling out the “serious onerous requirements the FDA has had making the process long and expensive for the makers of these biosimilar equivalents.” To Makary’s point, Europe stays markedly ahead of the U.S. when it comes to biosimilar approvals. As of March 2026, European regulators had signed off on 168 biosimilar products, while the U.S. tally stood at 90 as of January. In Europe, the “patent games and shenanigans that play out” are far less than in the U.S., Amin told Fierce. Part of this phenomenon, beyond the differences in the U.S. and Europe’s regulatory structure, comes down to the fact that “the U.S. market is the prize,” he explained. “It’s the crown jewel for the pharmaceutical company.” In the case of a company like Alvotech, securing a first-mover advantage is crucial, especially “in markets like the U.S., and some of the bigger markets in Europe,” Graver explained. As for how biosimilar outfits like Alvotech are embracing the recent onshoring boom in the U.S., Graver pointed to her company’s U.S. capacity tie-up with Fujifilm Biotechnologies earlier this year , adding that onshore production is “something that is part of our strategic vision.” Aside from appeasing requirements around U.S. trade and tariff policy, working directly with the current administration and other U.S. stakeholders could help solidify the market for Alvotech, Graver added. “Certainly, I think there will continue to be potential for procurement opportunities, and the government is a large procurer of pharmaceuticals, so it makes sense to continue to work with stakeholders within the government on putting some preferential procurement around products that are made end-to-end in the U.S.,” she explained. And recent policy considerations aside, the U.S. market is simply too big to ignore, with local manufacturing capacity handy either way, Graver pointed out. “Having the end-to-end supply chain within the U.S., especially for U.S.-destined products, gives more control, gives more flexibility, you can be more adaptive to demand shifts and changes,” she said. “We today produce out of our Reykjavik facility,” Graver explained. “Now, with the bolt-on in Fujifilm, it’s giving us a broader scope to be able to meet demand globally, but specifically for the U.S.” Further manufacturing moves, in Europe and especially the U.S., are something that Alvotech will “continue to look to do,” Graver added. Meanwhile, the prize in the U.S. biosimilar market is poised to become more tempting over the next 10 years as it enters a so-called “golden decade” that coincides with the looming “biosimilar void.” The dovetailing of the void and the golden decade present a potential $232 billion opportunity for biosimilar makers to get in on the over 100 biologic drugs that are set to lose patent protection through 2034, according to IQVIA . As of recently, only 10% of those drugs had biosimilar competition in development, however. This, Woollett says, is “why the efficiency of development matters,” and why cutting down on the requirements for expensive comparative studies is “particularly important.” “Nobody’s questioning do-ability. You can make biosims to any originator biologic,” Woollett said. “I think the science has asked and answered. We just have to implement more ... efficiently, such that we can rescue the void.” Compared to generics, where cheaper copies of reference products are abundant and hold a major place on the market, biosimilars simply “cost so much more to develop,” she said. To incentivize this costly development, “we need to create the commercial certainty that if you come up with an equivalent product at a lower price, you get market share.” Samsung Bioepis, looking to expand its portfolio by 20 products by 2030, has unleashed a host of biosimilar products across several markets in the past few months alone, including an Eylea biosimilar in Europe following a March settlement with Regeneron and Bayer and a Stelara biosim in Japan . This year, the company is expected to wrap up clinical studies of its potential Keytruda biosimilar following trial wins showing that the drug meets pharmacokinetic equivalence to Merck’s megablockbuster and achieved an equivalent objective response rate as well. Meanwhile, despite increased efforts to secure domestic supply for American-bound biosimilars, the bulk of biosimilars for the U.S. market continue to be produced abroad in countries such as South Korea, India and China, as well as in Europe, Alvotech’s Graver explained. In terms of working with the present administration and other U.S. policymakers, Graver said that both her company and others should seize the moment by building sustainable infrastructure for biosimilar production in the States, echoing Woollett’s concerns about the risky expense of current studies and biosimilar infrastructures. “I think one of the things that we’ve seen in the small molecule world is that sustainability changed over time, really resulting in a lot of offshoring,” she said. “I think biosimilars are still at that point in their lifecycle where those companies that have a robust pipeline, that are willing to enter markets first, form them early, have a real advantage from a cost basis for the U.S. patient base.” In theory, the market for biosimilars could rival that of original products due to unequal medicine access. For any biologic on the market, there’s still “a lot of people not getting these treatments,” according to Woollett. With increased education that speaks to patients' understanding of the availability of cheaper options, “then there’s a lot more people available,” Woollett said. “You’ve got a much bigger market.” Neion’s Li affirmed that high costs pinned to studies and manufacturing previously posed a significant barrier to entry for newcomers in the U.S. biosimilar industry. But the situation has improved some in recent years, he admitted, noting that switching studies have been increasingly waived for biosimilar developers. He wondered whether recent regulatory advances in the field might also see developers target a broader slate of development targets, rather than going after a few prize reference biologics all at once. “The pool of targetable biologics has increased just immensely,” he said. “I think you're going to see a lot more opportunity for product selection variations between companies, and the ability to find ‘niche’ opportunities, and so I think that's a very exciting thing for the space.”