Montana’s new “right to try” law can’t come soon enough for some
Montana’s new “right to try” law can’t come soon enough for some
蒙大拿州新的“尝试权”法对某些人来说来得太晚了
EXECUTIVE SUMMARY 执行摘要
Kris DeVault is desperate. His son, Brody, was born in March 2023. It wasn’t long before he started to show signs of developmental delay, says DeVault. As time went on, Brody started missing key milestones in speech, movement, and coordination, he says. Kris DeVault 感到绝望。他的儿子 Brody 出生于 2023 年 3 月。DeVault 说，没过多久，孩子就开始出现发育迟缓的迹象。他说，随着时间的推移，Brody 开始错过语言、运动和协调能力方面的关键发育里程碑。
When Brody was around two and a half years old, a genetic test revealed creatine transporter deficiency—a rare condition in which the brain and muscles lack the energy they need to develop. There are no cures for Brody’s condition. But DeVault has learned of a company developing a drug that might help. That drug is still in the early stages of development and has only been tested in animals and a small number of healthy adults. Doctors can’t prescribe it. DeVault knows the drug might not work. But he’s doing all he can to access it regardless. And a new law in Montana could make it easier for people in his position to get access to treatments—at least in theory. 当 Brody 大约两岁半时，基因检测显示他患有肌酸转运蛋白缺乏症（CTD）——这是一种罕见疾病，患者的大脑和肌肉缺乏发育所需的能量。目前尚无治愈 Brody 这种疾病的方法。但 DeVault 得知有一家公司正在开发一种可能有所帮助的药物。该药物仍处于早期开发阶段，仅在动物和少数健康成年人身上进行过测试。医生无法开具处方。DeVault 知道这种药可能无效，但他仍竭尽全力想要获得它。而蒙大拿州的一项新法律在理论上可以使像他这样处境的人更容易获得治疗。
Today, Brody is three years old. His dad describes him as a happy, curious, and loving little boy who wants to learn. But Brody struggles to communicate. “He’s got no words, really,” says DeVault. “He wants to communicate more than he’s able to … which then turns into frustration.” 如今，Brody 三岁了。他的父亲形容他是一个快乐、好奇、充满爱心且渴望学习的小男孩。但 Brody 在沟通方面存在困难。DeVault 说：“他几乎不会说话。他想要沟通的愿望超过了他的能力……这最终变成了挫败感。”
It’s difficult for Brody to tell his parents whether he’s hot, cold, hungry, thirsty, uncomfortable, or even in pain, says DeVault. He recently found Brody standing on an anthill in the backyard, being bitten by red ants. “These fire ants were just going to town on his feet … and he was just looking,” he says. DeVault 说，Brody 很难告诉父母他是热、冷、饿、渴、不舒服还是感到疼痛。最近，他发现 Brody 站在后院的蚁丘上，被红火蚁叮咬。“这些火蚁在他的脚上肆虐……而他只是看着，”他说。
Brody has muscle weakness too. “He can’t move very fast, he doesn’t have a ton of strength … and it takes a lot of energy for him to walk balanced,” says DeVault. “His arms are skinnier than [those of] his nine-month-old sister.” It’s concerning, but DeVault is most worried about Brody’s neurological development. Toddlers’ brains are exceptionally “plastic”—the first years of a child’s life are thought to be crucial for long-term brain development. Brody 还有肌肉无力的问题。“他移动速度不快，没有多少力气……而且他需要消耗大量能量才能保持平衡行走，”DeVault 说。“他的手臂比他九个月大的妹妹还要细。”这令人担忧，但 DeVault 最担心的是 Brody 的神经发育。幼儿的大脑具有极强的“可塑性”——人们认为孩子生命的最初几年对于大脑的长期发育至关重要。
A biotechnology company in France is working on a drug to help people like Brody. Creatine usually provides brain cells with energy. People with creatine transporter deficiency (CTD) can’t get creatine into the brain. The team at Ceres Brain Therapeutics is developing a treatment designed to bypass this issue and effectively deliver creatine directly to the brain. 法国一家生物技术公司正在研发一种药物来帮助像 Brody 这样的人。肌酸通常为脑细胞提供能量。患有肌酸转运蛋白缺乏症（CTD）的人无法将肌酸输送到大脑。Ceres Brain Therapeutics 的团队正在开发一种旨在绕过这一问题，并将肌酸有效直接输送到大脑的疗法。
So far, the team has seen promising results in mice, says Ceres CEO Thomas Joudinaud. The company also recently completed a phase I clinical trial that involved testing various doses of the drug, which is delivered as a nasal spray, in 48 healthy adult volunteers. That trial has not yet been published, says Joudinaud. The drug has not been tested in people with CTD, or in children. “I look at this, and I’m like, that is my one shot for Brody,” says DeVault. Ceres 首席执行官 Thomas Joudinaud 表示，到目前为止，该团队在小鼠身上看到了令人鼓舞的结果。该公司最近还完成了一项 I 期临床试验，在 48 名健康成年志愿者身上测试了该药物的不同剂量，该药物通过鼻喷雾剂给药。Joudinaud 说，该试验尚未发表。这种药物尚未在 CTD 患者或儿童身上进行过测试。“我看着这个，心想，这就是 Brody 的唯一机会，”DeVault 说。
Joudinaud is planning a phase II trial in people with CTD, as well as others with amyotrophic lateral sclerosis. But that trial will take place in France, and it’s unlikely that Brody will be able to take part, says DeVault. Ceres can’t make the drug available to Brody under an expanded access scheme run by the US Food and Drug Administration either, because the drug has not been registered with the FDA, and because it is currently manufactured in a way that does not comply with FDA regulations, says Joudinaud. Joudinaud 计划在 CTD 患者以及肌萎缩侧索硬化症（ALS）患者中进行 II 期试验。但 DeVault 说，该试验将在法国进行，Brody 很可能无法参加。Joudinaud 表示，Ceres 也无法通过美国食品药品监督管理局（FDA）的扩大使用计划向 Brody 提供该药物，因为该药物尚未在 FDA 注册，且目前的生产方式不符合 FDA 的规定。
Even if that phase II trial is successful, and if the drug is ultimately approved, it is unlikely to reach the US market for at least a few years. DeVault is worried that will be too late for Brody—he’ll be “past his plasticity window” by then, he says. Now, with the adoption of a new law in Montana, he theoretically has another option. 即使该 II 期试验取得成功，且药物最终获得批准，它至少也要几年后才能进入美国市场。DeVault 担心这对 Brody 来说太晚了——他说，到那时他将“错过大脑可塑性窗口期”。现在，随着蒙大拿州一项新法律的通过，他在理论上有了另一个选择。
Montana has had a “right to try” law—which allows terminally ill people to apply for access to unapproved drugs—in place since 2015. In 2023, a new law technically expanded this option to people who were not terminally ill, providing the drugs have been through preliminary phase I clinical trials. A second law aimed to clarify how clinics could sell and administer those treatments to patients. And last weekend, the state’s department of Health and Human Services finalized a set of rules for those clinics. 蒙大拿州自 2015 年起就实施了“尝试权”法，允许绝症患者申请使用未经批准的药物。2023 年，一项新法律在技术上将这一选择扩大到了非绝症患者，前提是这些药物已经通过了初步的 I 期临床试验。第二项法律旨在明确诊所如何向患者销售和管理这些疗法。上周末，该州的卫生与公众服务部为这些诊所敲定了一套规则。
An experimental treatment review board (ETRB) has been established to review applications for access to experimental, unproven, and unapproved drugs. And it is set to review its first two applications in the coming weeks. Ceres could also apply to Montana’s ETRB to sell its experimental treatment to Brody’s parents via a clinic in the state. But Joudinaud is reluctant, at least for the time being. While he thinks that Montana’s setup is “very interesting and very pragmatic” and “suitable for our drug,” he’s worried about getting on the wrong side of the FDA. 一个实验性治疗审查委员会（ETRB）已经成立，负责审查获取实验性、未经证实和未经批准药物的申请。它准备在未来几周内审查首批两份申请。Ceres 也可以向蒙大拿州的 ETRB 申请，通过该州的一家诊所向 Brody 的父母出售其实验性疗法。但 Joudinaud 目前还很犹豫。虽然他认为蒙大拿州的机制“非常有趣且非常务实”，并且“适合我们的药物”，但他担心会与 FDA 产生冲突。
DeVault has been pleading with FDA staffers for a written statement essentially promising that biotech companies participating in Montana’s program won’t be penalized later on, especially when they eventually try to get their drugs approved in the US. But he hasn’t made any progress. Now he’s looking beyond Montana. He’s considering accessing treatment in Próspera, a private city and “special economic zone” in Roatán, Honduras, where a clinic sells unproven stem-cell and gene therapies, among others. DeVault 一直在恳求 FDA 工作人员提供一份书面声明，承诺参与蒙大拿州项目的生物技术公司将来不会受到惩罚，特别是在他们最终试图在美国获得药物批准时。但他没有取得任何进展。现在，他开始将目光投向蒙大拿州之外。他正在考虑在洪都拉斯罗阿坦岛的私人城市和“经济特区” Próspera 寻求治疗，那里的一家诊所出售未经证实的干细胞和基因疗法等。
Many scientists have cautioned against the use of such “offshore” clinics. Even when it comes to Montana, scientists, bioethicists, and health law experts will caution that phase I clinical trials don’t prove a drug is safe. And they certainly don’t prove a drug’s efficacy, either. When I spoke to Aaron Kesselheim, a professor of medicine at Harvard Medical School with expertise in health policy and drug regulation, about the Montana law earlier this week, he made his concerns clear. “Patients who want these kinds of treatments deserve them to be rigorously assessed so that [they] can better understand what they’re getting themselves into.” 许多科学家警告不要使用此类“离岸”诊所。即使对于蒙大拿州的情况，科学家、生物伦理学家和卫生法专家也会警告说，I 期临床试验并不能证明药物是安全的。它们当然也不能证明药物的有效性。本周早些时候，当我与哈佛医学院医学教授、卫生政策和药物监管专家 Aaron Kesselheim 谈论蒙大拿州的法律时，他明确表达了自己的担忧。“想要这些疗法的患者理应得到严格的评估，这样他们才能更好地了解自己所面临的情况。”