第1890期:Another Alzheimer's Drug Showing Promise

Another experimental Alzheimer’s drug has been shown to slow patients’ worsening conditions, researchers reported Monday. The American drug company Eli Lilly said it is seeking U.S. Food and Drug Administration (FDA) approval for the drug donanemab. If approved, it would be the second Alzheimer’s treatment for delaying the disease. Alzheimer’s affects the brain and causes memory loss and dementia. The FDA approved Leqembi, from Japanese drugmaker Eisai, earlier this month. “Finally there’s some hope, right, that we can talk about,” Lilly’s Dr. John Sims told reporters Monday at the Alzheimer’s Association International Conference in Amsterdam, the Netherlands.

研究人员周一报道称，另一种实验性阿尔茨海默病药物已被证明可以减缓患者病情的恶化。美国制药公司礼来公司表示，正在寻求美国食品和药物管理局（FDA）批准其药物 donanemab。 如果获得批准，这将是第二种延缓阿尔茨海默病的治疗方法。 阿尔茨海默病会影响大脑并导致记忆丧失和痴呆。FDA 本月早些时候批准了日本制药商卫材 (Eisai) 的 Leqembi。礼来公司的约翰·西姆斯博士周一在荷兰阿姆斯特丹举行的阿尔茨海默病协会国际会议上对记者说：“终于有一些希望了，对吧，我们可以讨论一下。”

The drug does not cure the disease. Instead, it slows its progression by about four to seven months. But Sims noted that “it doesn’t mean you can’t have very meaningful treatments for patients.” Eli Lilly published the full results of its study of 1,700 patients in the Journal of the American Medical Association. It also presented its results at the Alzheimer’s conference. Both donanemab and Leqembi are laboratory-made antibodies. The treatments are injected into the patients. The drugs target a protein buildup, called beta amyloid, in the brain of Alzheimer’s patients. Both drugs come with serious safety concerns. Patients can experience brain swelling or bleeding. In the Lilly study, such side effects were linked to three deaths.

该药物不能治愈该疾病。 相反，它会减慢其进展约四到七个月。 但西姆斯指出，“这并不意味着你不能为患者提供非常有意义的治疗。”礼来公司 (Eli Lilly) 在《美国医学会杂志》上发表了对 1,700 名患者进行的研究的完整结果。 它还在阿尔茨海默病会议上展示了其研究结果。donanemab 和 Leqembi 都是实验室制造的抗体。 将治疗药物注射到患者体内。 这些药物针对的是阿尔茨海默病患者大脑中一种称为β淀粉样蛋白的蛋白质积聚。这两种药物都存在严重的安全问题。 患者可能会出现脑肿胀或出血。 在礼来公司的研究中，此类副作用与三人死亡有关。

Dr. Liana Apostolova was the study investigator. She is also a professor in Alzheimer's Disease research at Indiana University School of Medicine. She said, "These side effects should not be taken lightly." But she added that, in most cases, the effects were well controlled by monitoring with magnetic resonance imaging (MRI) or by stopping using the drug.Lilly’s study included people ages 60 to 85 who were in the early stages of Alzheimer’s. Half of the study subjects received a monthly injection of donanemab for up to 18 months. The other half received an inactive substance, called a placebo. Patients were also switched to inactive substances if enough amyloid cleared out. The study found that it happened to half of the patients within a year. Amyloid alone does not cause Alzheimer’s. So researchers also studied the levels of tau, another protein that causes the disease in the brain. Patients with higher levels of tau are considered to be in the more advanced stages of Alzheimer’s.

Liana Apostolova 博士是该研究的调查员。 她还是印第安纳大学医学院阿尔茨海默病研究的教授。 她说：“这些副作用不应掉以轻心。” 但她补充说，在大多数情况下，通过磁共振成像（MRI）监测或停止使用药物可以很好地控制效果。礼来公司的研究对象是年龄在 60 岁至 85 岁之间、处于阿尔茨海默病早期阶段的人。 一半的研究对象每月注射多南单抗，持续长达 18 个月。 另一半则接受一种称为安慰剂的非活性物质。如果清除了足够的淀粉样蛋白，患者也会改用非活性物质。 研究发现，一半的患者在一年内发生了这种情况。淀粉样蛋白本身并不会导致阿尔茨海默病。 因此，研究人员还研究了 tau 蛋白的水平，tau 蛋白是另一种导致大脑疾病的蛋白质。 tau 水平较高的患者被认为处于阿尔茨海默病的晚期阶段。

The results: both groups declined during the 18-month study but the drug appears to work better for patients in earlier stages of the disease. Those with low to medium tau levels saw a 35- percent slower decline. For high tau patients, donanemab slowed the disease progression by about 17 percent. Anne White is the president of neuroscience at Lilly. She said, "At the end of the trial, the average patient had been without drugs for seven months and yet they continued to benefit.” Scientists say that, while these drugs may mark a new era in Alzheimer’s treatment, huge questions remain about which patients should try them. Questions also remain about how much benefit patients will really experience. The main safety concern is brain swelling or bleeding. These conditions often cause no symptoms but sometimes can be serious, even deadly.

结果：在 18 个月的研究中，两组患者的病情均有所下降，但该药物似乎对疾病早期阶段的患者效果更好。 tau 水平低到中等的人的下降速度慢了 35%。 对于高 tau 蛋白患者，donanemab 将疾病进展速度减慢了约 17%。安妮·怀特 (Anne White) 是礼来公司神经科学总裁。 她说：“试验结束时，患者平均已经七个月没有服用药物，但他们仍然受益。”科学家表示，虽然这些药物可能标志着阿尔茨海默病治疗的新时代，但哪些患者应该尝试这些药物仍然存在巨大问题。 关于患者真正能得到多少好处仍然存在疑问。主要的安全问题是脑肿胀或出血。 这些情况通常不会引起任何症状，但有时可能很严重，甚至致命。

Another concern is that more than 90 percent of the study’s patients were white. That means there is little data on how effective the treatment could be for other populations, said Alzheimer’s specialist Jennifer Manly of Columbia University. Lilly expects the FDA to decide by the end of this year whether to approve donanemab. The company is also seeking approval from other health agencies worldwide.

另一个担忧是该研究中超过 90% 的患者是白人。 哥伦比亚大学阿尔茨海默病专家詹妮弗·曼利说，这意味着关于这种治疗对其他人群的有效性的数据很少。礼来公司预计 FDA 将在今年年底前决定是否批准 donanemab。 该公司还在寻求全球其他卫生机构的批准。