The FDA wants to pull its approval of a drug. It’s not so easy.

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In May 2021, the US Food and Drug Administration released a lengthy briefing document on an experimental medication for a rare autoimmune form of vasculitis that often damages the kidneys and lungs. The agency was on the fence about whether to approve the treatment, and it wanted an independent advisory committee to weigh in.

2021年5月，美国食品药品监督管理局（FDA）发布了一份关于一种实验性药物的长篇简报，该药物用于治疗一种常损害肾脏和肺部的罕见自身免疫性血管炎。当时，该机构对于是否批准这种疗法持观望态度，并希望由一个独立的咨询委员会进行评估。

Among the questions at hand: Was the drug meaningfully better than existing therapies? Participants in the study, which had been conducted by the California biotechnology company ChemoCentryx, did appear to have slightly higher rates of symptom remission after one year. But according to the FDA, it was hard to interpret the results because the study’s design had been less than optimal.

当时讨论的问题包括：该药物是否明显优于现有疗法？由加州生物技术公司ChemoCentryx进行的研究显示，参与者在一年后的症状缓解率似乎略高。但FDA认为，由于研究设计不够理想，很难对结果进行解读。

Some advisory committee members expressed a similar view. The effect of the drug, said one, “is just not well verified by this study.” At the same time, many patients, and some physicians, saw in the data a potentially helpful medication, one that might lessen patients’ reliance on steroids, which are highly effective but often cause severe side effects.

一些咨询委员会成员表达了类似的观点。其中一人表示，该药物的效果“在这项研究中并未得到充分验证”。与此同时，许多患者和一些医生从数据中看到了一种潜在的有效药物，它或许能减少患者对类固醇的依赖，尽管类固醇疗效显著，但往往会引起严重的副作用。

The advisory committee ultimately voted narrowly to recommend approval, and the FDA followed that advice, greenlighting the drug on October 7, 2021. The drug, marketed as Tavneos, started making its way into clinics. A year after approval, ChemoCentryx was acquired by Amgen, one of the world’s largest pharmaceutical companies.

咨询委员会最终以微弱优势投票建议批准，FDA采纳了这一建议，并于2021年10月7日批准了该药。这种以Tavneos为商品名的药物开始进入临床使用。获批一年后，ChemoCentryx被全球最大的制药公司之一安进（Amgen）收购。

The cost, even today, isn’t minor: $220,000 per year, according to Drugs.com. In fiscal year 2025, sales of Tavneos reached nearly half a billion dollars. This financial windfall has unfolded despite a long-roiling investor lawsuit—one that incidentally uncovered what the FDA today believes is evidence that ChemoCentryx employees manipulated the data in the pivotal trial submitted to the agency.

据Drugs.com显示，该药的费用至今仍不低：每年22万美元。在2025财年，Tavneos的销售额达到了近5亿美元。尽管面临一场长期发酵的投资者诉讼，该药仍获得了巨大的经济收益。而这场诉讼意外揭露了FDA目前认为的证据，即ChemoCentryx员工在提交给该机构的关键试验中操纵了数据。

In April of this year, the FDA issued a letter proposing that Tavneos be withdrawn from the US market, citing reports of serious, sometimes fatal, liver injury, and arguing that the drug now lacks “substantial evidence” that it works. These revelations have triggered a dramatic cascade of events.

今年4月，FDA发布了一封信函，建议将Tavneos撤出美国市场，理由是出现了严重甚至致命的肝损伤报告，并指出该药物目前缺乏证明其有效的“实质性证据”。这些披露引发了一系列剧烈的连锁反应。

This summer, the New England Journal of Medicine retracted a paper describing the clinical trial and Tavneos was taken off the market in the European Union. The United Kingdom has announced that it, too, will remove the product from the market. And on October 29, a court hearing is expected to proceed over Zoom to consider a proposed $69 million settlement for the lawsuit.

今年夏天，《新英格兰医学杂志》撤回了一篇描述该临床试验的论文，Tavneos也在欧盟被下架。英国也宣布将把该产品撤出市场。此外，预计10月29日将通过Zoom举行法庭听证会，审议一项拟议中价值6900万美元的诉讼和解方案。

But the fate of Tavneos, at least in the United States, is far from sealed. Amgen has pushed back against its critics, insisting that—whatever the details of ChemoCentryx’s data handling—its drug works as advertised and should stay on the market. In July, the company submitted a 104-page document to the FDA stating that “the totality of the evidence supports the continued availability of TAVNEOS.”

但Tavneos的命运，至少在美国，远未盖棺定论。安进公司反驳了批评者，坚称无论ChemoCentryx在数据处理细节上如何，其药物的效果正如宣传的那样，应该继续留在市场上。7月，该公司向FDA提交了一份104页的文件，称“全部证据支持TAVNEOS继续供应”。

Some patients and academic experts also believe the drug is an important treatment option. “This appears to be an efficacious medication,” said Eric Roberts, an epidemiologist at the University of California, San Francisco, who co-authored an independent registry study of Tavneos.

一些患者和学术专家也认为该药是一种重要的治疗选择。加州大学旧金山分校的流行病学家埃里克·罗伯茨（Eric Roberts）表示：“这似乎是一种有效的药物。”他曾参与撰写了一项关于Tavneos的独立登记研究。

The dispute is emblematic of the FDA’s longstanding struggle to regulate drugs of uncertain efficacy, said Reshma Ramachandran, a physician and co-director of the Yale Collaboration for Regulatory Rigor, Integrity, and Transparency. Absent more rigorous studies, either before or after a drug goes on the market, Ramachandran worries, “we’re just going to be living in uncertainty in terms of whether or not these drugs actually work.”

耶鲁大学监管严谨、诚信与透明度合作项目（Yale Collaboration for Regulatory Rigor, Integrity, and Transparency）的医生兼联合主任雷什玛·拉马钱德兰（Reshma Ramachandran）表示，这场争议是FDA在监管疗效不确定的药物方面长期挣扎的缩影。拉马钱德兰担心，如果缺乏更严谨的研究（无论是在药物上市前还是上市后），“我们对于这些药物是否真的有效将始终处于不确定之中。”

For American consumers, the saga of Tavneos also raises potent questions around the safeguards in place to ensure the integrity of drug approvals, particularly when a relatively small company conducts the pivotal trial and has so much riding on the success of a single drug.

对于美国消费者而言，Tavneos的事件也引发了关于确保药物审批完整性的保障措施的严峻问题，尤其是当一家相对较小的公司进行关键试验，且其命运完全系于单一药物的成功时。

Chloe Cusano was a 20-year-old college student when she was struck, this past December, with unbearable pain in her legs, as well as bouts of breathlessness from routine tasks like walking upstairs or bending down to retrieve her dog’s water dish. After going to the emergency room, she was hospitalized for more than two weeks, during which she was diagnosed with ANCA-associated vasculitis, or AAV, an umbrella term for a group of rare diseases in which the immune system mistakenly attacks its own blood vessels.

克洛伊·库萨诺（Chloe Cusano）去年12月还是一名20岁的大学生，当时她感到双腿剧痛难忍，且在进行上楼或弯腰拿狗水盆等日常活动时会感到呼吸困难。在去急诊室后，她住院了两周多，期间被诊断出患有ANCA相关性血管炎（AAV），这是一个统称，指一组免疫系统错误攻击自身血管的罕见疾病。

When it was first identified, the condition was usually fatal. Over the past four decades, scientists have developed drugs that allow many AAV patients to live a relatively normal lifespan. Because the disease can rapidly lead to organ failure, particularly of the kidneys and lungs, patients are immediately started on a high dose of steroids to rapidly tamp down inflammation. They also typically receive slower-acting medications that target the underlying disease process.

这种疾病在最初被发现时通常是致命的。在过去的四十年里，科学家们开发出的药物使许多AAV患者能够拥有相对正常的寿命。由于该病可迅速导致器官衰竭（尤其是肾脏和肺部），患者通常会立即开始接受大剂量类固醇治疗，以迅速抑制炎症。他们通常还会接受针对潜在疾病过程的起效较慢的药物。

Steroids, however, have severe side effects. Within a month and a half of going on the steroids, Cusano recalled, she gained 40 pounds. Her emotions were “just like crazy,” swinging from intense sadness to anger. She had trouble falling asleep, and when she did fall asleep, she was haunted by another side effect: nightmares. “I did not like it at all,” she recalls. AAV patients may need to take steroids for months to years, and Tavneos was supposed to replace or reduce their use.

然而，类固醇有严重的副作用。库萨诺回忆说，在使用类固醇的一个半月内，她体重增加了40磅。她的情绪“简直疯了”，在极度悲伤和愤怒之间摇摆。她难以入睡，即使睡着了，也会被另一种副作用困扰：噩梦。“我一点也不喜欢它，”她回忆道。AAV患者可能需要服用类固醇数月甚至数年，而Tavneos本应取代或减少其使用量。

David Pisetsky, a rheumatologist and researcher at the Duke University School of Medicine, was on the FDA advisory committee that considered the ChemoCentryx trial data. He voted against recommending approval, in part because many patients in the control group received just one round of a slower-acting medication — rituximab — in addition to steroids when, in the real world, they would have received two, according to Pisetsky. The trial’s design, he said, made the results difficult to interpret. In an edit

杜克大学医学院的风湿病学家兼研究员大卫·皮塞茨基（David Pisetsky）曾是审议ChemoCentryx试验数据的FDA咨询委员会成员。他投票反对批准，部分原因是据皮塞茨基称，对照组中的许多患者在类固醇之外仅接受了一轮起效较慢的药物——利妥昔单抗（rituximab）治疗，而在现实世界中，他们本应接受两轮。他说，该试验的设计使得结果难以解读。（在编辑中）