Adalimumab-ATTO(Amgen)

“There's just too many question marks because of the complexities that we have in the U.S. market that have slowed adoption of biosimilars,” Samsung Bioepis’ head of U.S. commercial, Thomas Newcomer, said in an interview. It’s been more than 10 years since the FDA signed off on the U.S.’ first biosimilar product, opening up what was originally expected to be an easily accessible, cheaper drug market featuring heightened competition and potential new savings for patients.Now, more than 80 biosimilar approvals later, the promise of broad biosimilar adoption and lower drug prices hasn’t played out as initially anticipated, leaving the biosimilar market at a critical inflection point as it enters 2026, with policy changes and major patent cliffs creeping ever closer. 2025 was marked by “extraordinary change and progress within the biosimilar landscape,” highlighting both the opportunities and the challenges facing the field, Samsung Bioepis’ head of U.S. commercial, Thomas Newcomer, said in the company’s fourth-quarter biosimilar market report. Samsung Bioepis, which tracks the biosimilar market on a quarterly basis, found that only 73% of the U.S.’ 80 approved biosimilars launched as of September 2025. Several of the offerings awaiting a market rollout are biosimilars to Regeneron’s blockbuster Eylea, setting up a showdown in 2026 as cheaper copycats close in on the lucrative ophthalmology market.  Biosimilar beginningsThe rise of biosimilars is a relatively modern development in the history of the biopharma industry following the establishment of their regulatory pathway through the Biologics Price Competition and Innovation Act in 2010. The legislation, part of the Affordable Care Act, took inspiration from the Hatch-Waxman Act of 1984, which facilitated a booming generic drug market that today sees nearly 90% of U.S. prescriptions filled by lower-cost generics, according to the Pharmaceutical Research and Manufacturers of America.But the last 10 years of biosimilar uptake suggest the traditional market model for small-molecule generic medicines doesn’t quite fit on the biologics side, Melanie Whittington, Ph.D., head of Leerink Partners’ MEDACorp Center for Pharmacoeconomics, explained in a recent interview with Fierce Pharma. According to Whittington, research suggests that biosimilars don’t cause as rapid or as steep of a price drop for their reference products in the initial few years of market entry. Newcomer, for his part, points to an average five-year price decrease driven by biosimilars of 52% across different therapeutic areas, although uptake is “variable,” he said in an interview.Much of this variability has to do with the types of drug and the patient needs that each biosimilar product fills. For example, the adoption rate for oncology biosimilars, which may not treat patients for extended periods, is “very high,” Newcomer said. But biosimilars for chronic immunology diseases are seeing what appears to be “consistently slower uptake,” he said.It’s likely that this disparity is related to the long-term duration of therapy for chronic diseases versus treatments for cancers or other acute diseases. If a patient has had a positive experience with a brand-name drug for many years, they likely would be more hesitant to make the switch to a biosimilar. Due in part to this hesitancy and a broader lack of biosimilar awareness, “we just see patients continue on the reference product month after month, which to the patient means they could be paying hundreds to thousands of dollars more every month,” Newcomer said at an November event.Even if pricier, a positive association with a branded reference product can be a deeply entrenched dissuasion to biosimilars. In fact, Truveta Research found in June that more than 1 in 8 patients who switched to a Humira biosimilar ended up switching back to the original product. Truveta also attributes this in part to fear or uncertainty, especially for older adults whose doctors may be taking increased caution to “keep them on a treatment that’s already working well.” In any case, biosimilar and generic market entry is a concept that’s fairly unique to the biopharmaceutical industry, Whittington points out.“We don’t typically think of things that literally can substantially drop in price overnight,” she said. “And biosimilars can do that.”For patients and payers, this highlights the great promise of biosimilar drugs that challenge pricey blockbusters. When these drugs near the end of their patent protection, a line of biosimilar versions often waits in the wings to storm the market and capture a piece of the sales pie. Competition among these biosimilar offerings often comes down to interchangeability tags, pricing strategies and launch timing. Humira lessons and a Stelara futureThe first few marketed biosimilars to a major blockbuster typically reap the most rewards. Amgen, which was the first to roll out biosimilars for AbbVie’s Humira, Johnson & Johnson’s Stelara and Regeneron's Eylea, sees a major opportunity in being among the “first wave” of biosim launches, commercial head Murdo Gordon said on a February call.But if biosimilar market watchers have learned anything over the past few years, it’s that there is no one-size-fits-all handbook for biosimilar market dynamics. In the case of launch timing, some companies are “figuring out ways to make it work,” even if they launch later in the competitive sequence, Newcomer said.Biosimilar manufacturers are also adapting beyond a two-price strategy. First conceived by Biocon and Viatris for the marketing of Semglee, a biosimilar version of Sanofi’s Lantus that was the first interchangeable biosimilar, the strategy hinges on marketing both a brand-name and an unbranded biosimilar. The unbranded version is priced at a sharp discount to the reference product, while the branded offering comes at less of a discount. The idea is that the two price points can cater to different players in the healthcare system.Ultimately, in Semglee's case, the higher-priced option became more popular due to larger rebates associated with the costlier product. This strategy was widely embraced in the Humira biosimilar realm, with first-to-market Amgen kicking things off with two versions of Amjevita.However, this two-price practice may soon become a relic of the past.In the now-aging Humira biosimilar landscape, some companies have opted to discontinue their higher-priced versions, with the market showing that there “may not be a need for both versions,” Newcomer noted. Only a handful of Humira biosimilars with a higher wholesale acquisition cost (WAC) remain, while the newer collection of Stelara biosimilars includes only one contender that utilized a dual WAC in Amgen’s Wezlana.Given what is looking to be an overarching shift away from the dual-price model, it appears that the market “has decided that low WAC biosimilars are going to be the way moving forward,” Newcomer mused.This could be a result of biosimilar makers coming to the conclusion that biosimilar adoption “required much more than just cost differentiation,” Kayli Kopil, a senior market research analyst at MMIT, wrote in a July report. In response, some drugmakers abandoned the dual-price strategy and pursued market share gains by “working with pharmacy benefit managers (PBMs) rather than against them,” Kopil said. This materialized in the form of partnerships featuring private-label biosimilars.The private-label strategy, also called “white-labeling,” is already a prominent route that Stelara biosimilars have taken, as PBMs “came prepared” for the wave of Stelara copies following a “chaotic” Humira biosimilar rollout, Adam Fein, Ph.D., president of the Drug Channels Institute, wrote in a July article.PBMs utilize private labels to include their own partnered biosimilars on their formularies, a move originating with CVS Health’s biosimilar arm Cordavis in 2023. CVS linked up with Sandoz to roll out its co-labeled Humira biosimilar Hyrimoz across all its formularies, kicking off branded Humira and quickly sending Hyrimoz prescriptions skyrocketing. Today, the three major PBMs favor their own private-label Humira biosimilars and led with their private-label Stelara biosimilars as the drug’s biosimilar market opened up in 2025.  "The overall shift toward private-label biosimilars is evident,” Kopil wrote. "PBMs now hold more control than ever before in the biosimilar landscape.”To stay with the times, it may even be necessary for smaller drugmakers to seek out such PBM-manufacturer alliances to preemptively secure market positioning before committing to development, MMIT analyst Benjamin Hinton warned in a 2024 report.As for interchangeability, the competitive edge that an interchangeable label can offer is likely to wane through the FDA’s new plan to increase the availability of U.S. biosimilars. Policy reform and the biosimilar voidThrough a draft guidance document released in late October, the FDA outlined its framework to reduce clinical testing burdens for biologic drug copies and to slap an interchangeability tag on all approved biosims. As it stands, biosimilars that are deemed interchangeable may be freely swapped out in place of a brand-name product at the pharmacy counter without a doctor's approval. In its guidance, the FDA pointed out that while biologic medicines make up only 5% of the prescriptions written in the U.S., they account for 51% of the country’s drug spending.Lawmakers and advocacy groups alike have been pushing for updates to the current interchangeability structure based on concerns that the separate tags could be muddying treatment decisions and blocking biosimilar uptake. The FDA’s plan suggests that comparative efficacy studies, which are currently necessary to prove interchangeability, may be done away with in the future.This stands to cut development time and costs in half, Andrew Bourgoin of the Bourgoin Insights Group wrote in a late October All Things Biosimilar report. The FDA’s efforts coincide with a key moment for the field in the so-called “biosimilar void,” a “pressing, urgent situation that threatens the very viability of our industry,” Juliana Reed of the Biosimilars Forum pointed out in a statement last fall.Over the next 10 years, 118 biologics are expected to lose patent protection, together totaling a $232 billion opportunity for biosimilars, according to an IQVIA report. Only 12 of those 118, however, have biosimilars currently in development. The remaining 106 with no biosimilar competition on the horizon make up what has been coined the “biosimilar void.”The threat of the biosimilar void is representative of the challenges that today hinder biosimilar development. IQVIA, in its February report, listed these factors as complex regulatory requirements, slow market adoption, high investment costs, reimbursement dynamics and evolving policy creating market unpredictability.It’s for these reasons that not many companies have signed up to join the “massive opportunity” the biosimilar void presents, save for a handful of biosimilar manufacturers that are “committed to the long haul,” Newcomer said.“There's just too many question marks because of the complexities that we have in the U.S. market that have slowed adoption of biosimilars,” he explained.Meanwhile, ever-evolving policy can make hefty development costs even harder to justify. For example, mandated government pricing reductions under the Inflation Reduction Act (IRA) served as a blow to the biosimilar makers that were developing versions of some of the medicines on the list, he said.“There’s a real risk that if reference prices are capped too low, biosimilars lose their competitive edge,” William Fleming said in Samsung Bioepis’ state of the market report. Fleming, a senior advisor at Petauri Health, previously held leadership roles at Humana. As Newcomer puts it, "the question mark becomes, are you ever going to get your development costs back?” Using the biosimilar 'tool'If the first 10 years of the biosimilar market set the foundation, the next decade will be instrumental in determining its capacity for future growth, especially as closely watched patent expirations near.One key priority, Newcomer says, is building awareness. The general public is well aware of what a generic medicine is, but the same can’t be said for biosimilars. If patients knew of other, lower-cost options, broader uptake would likely follow. Especially for chronic diseases and long-term therapies, “we don’t think that conversation is taking place,” he said. Samsung Bioepis, for one, attributes its continued investment in biosimilar development to a belief that biosimilars help lower the overall cost of healthcare in the U.S., Newcomer said.“Everybody’s looking for a fix,” he said, referencing the widespread goal of “fixing” the U.S. healthcare system and pointing to pricing policies such as the IRA and, more recently, most-favored-nation drug pricing.Beyond the potential behind such policies, “we’re not using the tools that are in front of us right now,” Newcomer explained, referring to the biosimilar drug market. “We have to start using this tool.”  

2026年1月5日，Zenas Biopharma公布了核心产品Obexelimab在治疗IgG4相关疾病（IgG4-RD）的III期研究结果。 从公告来看，这项名为INDIGO的研究非常漂亮，不仅达到了主要终点，连带着四个关键的次要终点也全线飘红。这本来意味着全球即将迎来首个靶向B细胞通路的一线新疗法，公司也紧接着宣布要在今年二季度向FDA提交上市申请。 然而，资本市场的反应却像一盆冷水：消息公布当天，Zenas的股价直接暴跌了52%。在现在的生物医药圈，仅仅拿到一个统计学上的“成功”已经远远不够了，市场更看重你在这个赛道里到底有没有稀缺性和统治力。 我们要先聊聊IgG4-RD这个病。它是一种慢性炎症，会引起组织纤维化，累及全身多个器官。这个病的驱动核心是体内一种特定的B细胞和浆细胞乱跑，在组织中引发炎症。 虽然这个病挺折磨人，但在美国只有2到4万名患者，属于典型的小众市场、小适应症。目前，FDA只批准了一款药物，就是安进的CD19单抗Uplizna。Uplizna于2025年4月获FDA批准率先上市，今年该适应症销售额预计在1亿美元左右。这意味着Obexelimab得在疗效、安全性或依从性上超过Uplizna才能有市场。 Obexelimab的机理确实很独特，它不是那种简单的“杀伤性”武器。它是一种双功能抗体，一边结合CD19，一边结合B细胞表面的抑制性受体FcγRIIb。 简单来说，它利用了人体自身的免疫反馈机制：当系统觉得抗体够多时，就给B细胞发信号让它“安静”下来。 相比传统的疗法直接把B细胞杀光（耗竭），Obexelimab只是在病理活动期“灭活”B细胞，等警报解除了，B细胞还能恢复自然功能。这种“非耗竭性”抑制听起来非常高级，理论上安全性也更高。 这个机制可以说是全新的，也符合逻辑的。正是这个原因，才有了市场对Obexelimab的极高期待：一是其创新的作用机制具备显著的差异化优势，二是该产品已成功吸引了多家重量级资本的战略投入与支持。 值得一提的是Obexelimab其实并不是 Zenas 自己开发的，而是从 Xencor 公司BD过来的。早在 2021 年底，刚起步的 Zenas 就砸下总价 4.8 亿美元的重金，拿下了这款药的全球开发权益。在那时候的市场环境下，Zenas 显然是想靠 Obexelimab 这种“不伤敌一千也能自损八百”的差异化机理，在自免赛道里讲出一个全新的故事。 靠着这个独特的作用机理，Zenas的 BD能力确实拉满了，到处寻找合作。2023 年 9 月，他们先把亚太六国的权益卖给了大厂 BMS，换回了 5000 万美元的真金白银；到了 2025 年 9 月，更是以5.5% 未来销售分成为代价和 Royalty Pharma 签了一份高达 3 亿美元的“对赌”融资。 那临床数据到底怎么样呢？ 在这次III期试验里，Obexelimab把复发风险降低了56%，看着还行，但对比一下对手就尴尬了。安进的Uplizna能把复发风险降低87%，而且Uplizna治疗组的复发比例只有10%左右，Obexelimab却高达27%。 这说明Obexelimab这种温和的“抑制”在力度上确实不如直接“清空”B细胞来得干脆。在IgG4-RD这种容易导致器官受损的病面前，医生和患者显然更看重谁能更彻底地防止复发。 再看给药方式，Obexelimab主打的是“居家皮下注射”，每周打一针。而Uplizna是每半年打一次。虽然居家注射看似方便，但由于Obexelimab为了增强抑制力对Fc段做了改造，反而牺牲了抗体的半衰期，导致给药频率非常高。对于患者来说，一年打52针和一年跑两趟医院，后者的依从性其实更高。 另外，相比半年一次的Uplizna，周制剂Obexelimab的药物成本要上升数十倍。 而且，Obexelimab除了这个小众病，还布局了红斑狼疮（SLE）和多发性硬化症（RMS），但在红斑狼疮的IIa期临床里，它连统计学终点都没达到。在这些大赛道上，它面对的是已经成名的阿达木单抗或者贝利尤单抗，赢面非常小。 除了这个核心产品，Zenas手里还有从诺诚健华引进的BTK抑制剂奥布替尼。这个药主要攻坚多发性硬化症（MS）里最难啃的两个地盘：PPMS和非活动性SPMS。 奥布替尼的优势在于它入脑能力极强，能穿透血脑屏障去清理大脑内部的炎症，这比那些进不去的单抗类药物更有想象力。 然而，BTK抑制剂现在面临一个全行业的“死穴”，就是MS患者肝毒性。就在2026年1月，FDA刚刚拒绝了赛诺菲同类药物Tolebrutinib的上市申请，原因就是出现了严重的肝损伤甚至肝移植病例。 虽然奥布替尼在血液瘤患者身上很安全，但在MS患者这种特定的免疫背景下，它在II期试验里也出现了类似的安全信号。对于需要几十年服药的自免病人来说，监管机构对肝毒性的容忍度极低。即使奥布替尼的病灶减少率比对手高，但只要安全性这把达摩克利斯之剑悬在头上，它的获批和商业化就存在巨大的变量。 Zenas剩下的管线，比如同样BD自诺诚健华的口服IL-17抑制剂ZB021，虽然口服药在百亿美金规模的IL-17市场很有诱惑力，但它的进度实在太慢了。目前ZB021还处于IND阶段，而前面礼来、赛诺菲、歌礼制药的产品已经跑到了二期甚至三期。等ZB021出来，市场可能早就被瓜分完了。 至于那个透脑TYK2抑制剂ZB022，神经炎症领域本身就是研发的“坟场”，机理复杂且失败率极高，目前连临床疗效数据都没有，很难评估成药性。 最后看估值，连续大跌之后，Zenas的市值来到了9亿美金左右。虽然跌了一半，但结合现有资产来看，它依然不便宜。 核心产品Obexelimab在小赛道里打不过安进，在大赛道里又缺乏统治力。 奥布替尼治疗MS虽然有潜力，但肝毒性这道红线极难跨越。剩下的管线要么进度落后，要么风险巨大。对于这种核心资产竞争力被证伪、后续管线又接不上的公司，9亿美金的市值暂时还看不到足够的吸引力。 最后，创新药行业规则就是这么简单而残酷，对未满足市场的绝对统治力才能有高溢价。