多纳奈单抗被视为治疗痴呆症的转折点

https://www.bbc.com/news/health-66221116

一种新药多南单抗 (donanemab)可以减缓认知能力下降，被誉为抗击阿尔茨海默病的转折点。

抗体药物通过清除这种痴呆症患者大脑中积聚的蛋白质，在疾病的早期阶段发挥作用。

虽然还不是一种治愈方法，但慈善机构指出（charities say ）在 美国医学会杂志 上发表的研究结果，标志着阿尔茨海默氏症治疗的新时代。 

英国药品监管机构已开始评估其是否可能在 NHS （英国国家医保）中使用。

该药物对阿尔茨海默病有效，但对其他类型的痴呆症无效，例如血管性痴呆。

在试验中，它似乎使疾病的进展速度减慢了约三分之一，使病人能够继续更多的日常生活和事务，例如做饭和享受爱好。 

80 岁的迈克·科利 (Mike Colley) 是英国仅有的几十名参加全球试验的患者之一。他和他的家人接受了 BBC 的独家采访。

迈克每个月都会在伦敦的一家诊所接受输液治疗（gets an infusion ），并说他是“你见过的最幸运的人之一”。

迈克和他的家人在他开始接受试验治疗前不久，就注意到他在记忆和决策方面存在问题。 

他的儿子马克说，一开始看到父亲的状况，很难受：“看到他处理信息和解决问题时，非常困难。但我认为现在（父亲的认知）下降已经达到了稳定水平。”

来自肯特郡的迈克说：“我每天都感觉更加自信。”

Donanemab是由礼来公司 (Eli Lilly) 生产的，与由卫材 (Eisai) 和百健 (Biogen) 公司开发的Lecanemab的作用方式相同--Lecanemab 成为了世界各地的头条新闻 当它被证明可以减缓老年痴呆疾病时。

尽管这些药物非常有前景，但它们并不是没有风险的治疗方法。 

donanemab试验中，多达三分之一的患者出现脑肿胀的常见副作用。对于大多数人来说，这个问题得到了解决，并且没有引起任何症状。然而，两名志愿者，可能还有第三名，因危险的大脑肿胀而死亡。

另一种抗体阿尔茨海默病药物，称为 aducanumab，最近由于安全问题和缺乏证据表明它对患者足够有效，被 被欧洲监管机构拒绝 。 

在donanemab试验中，研究人员对 1,736 名年龄在 60 岁至 85 岁之间患有早期阿尔茨海默病的人进行了检查。

其中一半人每月接受一次输注治疗，另一半则在 18 个月内接受模拟药物（也称为安慰剂）。

调查结果显示：

• 该药物似乎具有有意义的益处，至少对某些患者而言

• 就脑部扫描显示的清除率而言，那些患有较早疾病且基线时大脑淀粉样蛋白较少的人获得了更大的益处

• 服用药物的人还保留了更多的日常生活，例如能够讨论时事、接听电话、或追求兴趣爱好

• 根据人们仍能进行日常活动来判断，这种疾病的（发展）速度总体上减慢了约20%-30%；而在研究人员认为更有可能做出反应的一组患者中，疾病的（发展）速度减慢了 30%-40%

• 有明显的副作用，患者需要意识到治疗的风险 

• 一半接受多南单抗的患者能够在一年后停止治疗，因为它已经清除了足够的脑沉积物

专家警告说，淀粉样蛋白只是阿尔茨海默病复杂情况的一部分，目前尚不清楚这种治疗是否会在较长时间内继续产生更大的影响。 

他们说，这种药物的作用可能不是太大，但结果进一步证实，从大脑中去除淀粉样蛋白可能会改变阿尔茨海默氏症的病程，如果在正确的时间接受治疗，可以帮助受这种毁灭性疾病影响的人们。

英国痴呆症研究所的贾尔斯·哈丁厄姆教授表示：“今天看到这些结果的完整发表真是太棒了。 

“我们已经等待阿尔茨海默氏症的治疗方法很长时间了，因此看到该领域不断加快步伐的切实进展确实令人鼓舞。” 

苏珊·科尔哈斯博士表示：“今天的宣布标志着另一个里程碑。 

“经过数十年的研究，痴呆症的前景及其对人类和社会的影响终于发生了变化，我们正在进入一个阿尔茨海默病可以治疗的新时代。”

前首相戴维·卡梅伦在接受 BBC 广播四台的 PM节目采访时表示，应该投入资源进一步研究他所说的“大脑他汀类药物”。 

“我们想要一种药物，大脑中积聚这些蛋白质的人可以每天或每周服用，以将这些蛋白质从大脑中清除，从而减少患上导致痴呆症的疾病的机会，”他说。

当被问及政府是否准备在需要的地方进行投资以推出新疗法时，卡梅伦表示，这样做确实有动力：“我们是一个拥有六千万人口的国家，有一百万人患有痴呆症，其中许多人患有痴呆症。寄宿护理设施非常昂贵，因此有效治疗患者可以节省大量资金……我希望我们的系统能够实现这一目标。”

Lecanemab在美国获得许可的价格约为 27,500 美元（21,000 英镑）。 

目前尚不清楚多纳奈单抗在英国需要花费多少费用、以及获得批准需要多长时间，但阿尔茨海默病专家表示，拥有两种药物将有助于促进价格竞争。 

英国药物监管机构 NICE 表示，已经开始评估多纳奈单抗治疗阿尔茨海默病引起的轻度认知障碍或轻度痴呆的效果。

：“我们的目标是在尽可能接近其获得英国许可证的情况下，就其在 NHS 中的使用提出建议。”

迈克·科利 (Mike Colley) 于 4 月迎来 80 岁生日。在他的生日聚会上，他在 40 名客人面前唱起了《My Way》，给家人带来了惊喜。 

他告诉 BBC 新闻：“这就是我现在的信心。即使在 12 个月前，我也绝不会这么做。” 

他的儿子马克补充道：“我从没想过我会再次看到我的父亲如此充满活力。那是一个令人难以置信的时刻。”

Re:Cognition Health的神经放射学家顾问兼医疗总监Emer MacSweeney博士在英国领导了多南单抗的试验。

她说：“这确实意义重大，也是最大的突破之一。”

阿尔茨海默氏症协会表示：“这确实是抗击阿尔茨海默氏症的一个转折点，科学证明可以减缓这种疾病的发展。” 

如果这些新兴的阿尔茨海默病新疗法获得批准使用，英国大约 72 万人可能会受益，但阿尔茨海默病协会表示，NHS“根本没有准备好提供这些疗法”。 

该慈善机构首席执行官凯特·李 (Kate Lee) 表示：“及时、准确的诊断至关重要，目前英格兰和威尔士只有 2% 的人通过专业调查获得诊断，才有资格接受这些治疗。

“除此之外，这些新兴的阿尔茨海默病药物需要定期输注和监测，而 NHS 尚未具备大规模做到这一点的能力。”

Drug donanemab seen as turning point in dementia fight

https://www.bbc.com/news/health-66221116

A new drug, donanemab, is being hailed as a turning point in the fight against Alzheimer's, after a global trial confirms it slows cognitive decline.

The antibody medicine helps in the early stages of the disease by clearing a protein that builds up in the brains of people with this type of dementia.

Although not a cure, charities say the results in the journal JAMA mark a new era where Alzheimer's can be treated. 

The UK's drugs watchdog has started assessing it for possible NHS use.

The drug works in Alzheimer's disease, not in other types of dementia, such as vascular dementia.

In the trials, it appears to have slowed the pace of the disease by about a third, allowing people to retain more of their day-to-day lives and tasks, such as making meals and enjoying a hobby. 

Mike Colley, who is 80, is one of only a few dozen patients in the UK to take part in the global trial. He and his family spoke exclusively with the BBC. 

Mike gets an infusion each month at a clinic in London and says he is "one of the luckiest people you'll ever meet".

Mike and his family noticed he was having problems with memory and decision-making, not long before he started on the trial. 

His son, Mark, said it was very hard to watch at the beginning: "Seeing him struggle with processing information and solving problems was very hard. But I think the decline is reaching a plateau now."

Mike, who is from Kent, said: "I feel more confident every day."

Donanemab, made by Eli Lilly, works in the same way as lecanemab - developed by companies Eisai and Biogen - which created headlines around the world when it was proven to slow the disease.

Although extremely promising, these drugs are not risk-free treatments. 

Brain swelling was a common side-effect in up to a third of patients in the donanemab trial. For most, this resolved without causing symptoms. However, two volunteers, and possibly a third, died as a result of dangerous swelling in the brain.

Another antibody Alzheimer's drug, called aducanumab, was recently rejected by European regulators over safety concerns and a lack of evidence that it was effective enough for patients. 

In the donanemab trial, researchers examined 1,736 people aged 60 to 85 with early-stage Alzheimer's.

Half of them received a monthly infusion of the treatment and the other half were given a dummy drug, also known as a placebo, over 18 months.

The findings show:

• The drug seems to have a meaningful benefit, at least for some patients

• Those who had earlier disease and less brain amyloid at baseline derived greater benefit, in terms of clearance seen on brain scans

• Those given the drug also retained more of their day-to-day lives such as being able to discuss current events, answer the phone or pursue hobbies

• The pace of the disease, judged by what people could still do day-to-day, was slowed by about 20-30% overall - and by 30-40% in a set of patients who researchers thought more likely to respond

• There were significant side-effects and patients will need to be aware of risks of treatment 

• Half of patients on donanemab were able to stop the treatment after a year, because it had cleared sufficient brain deposits

Amyloid is just one part of the complex picture of Alzheimer's, and it is unclear if the treatment will continue to make more difference over a longer period, experts caution. 

The drug's effects may be modest, but the results provide further confirmation that removing amyloid from the brain may change the course of Alzheimer's, and help people affected by this devastating disease if they're treated at the right time, they say. 

Prof Giles Hardingham from the UK Dementia Research Institute said: "It is terrific to see these results published in full today. 

"We have waited a long time for Alzheimer's treatments, so it's really encouraging to see tangible progress continuing to gather pace in the field." 

Dr Susan Kohlhaas, from Alzheimer's Research UK, said: "Today's announcement marks another milestone. 

"Thanks to decades of research, the outlook for dementia and its impact on people and society is finally changing, and we're entering a new era where Alzheimer's disease could become treatable."

Speaking to BBC Radio 4's PM programme, former Prime Minister David Cameron said resources should be put towards further research into what he called a "statin for the brain". 

"We want a pill that people who have the build-up of these proteins in the brain can take every day or every week in order to clear those proteins out of the brain and therefore reduce your chances of getting a disease that causes dementia," he said.

Asked if the government were prepared to invest where needed to roll out new treatments, Mr Cameron said there was a real incentive to do so: "We're a country of sixty million people, with a million people with dementia, many of them in very expensive residential care settings and so there is a lot of savings to be had from effectively treating people….I'm hopeful that our system can deliver."

Lecanemab costs around $27,500 (£21,000) in the US, where it is licensed. 

It is not clear how much donanemab may cost and how long it might take to get approval in the UK, but Alzheimer's experts said having two drugs would help promote competition on price. 

The UK's drug's watchdog NICE says it has already started work on its appraisal of donanemab for treating mild cognitive impairment or mild dementia caused by Alzheimer's disease.

"Our aim is to produce recommendations on its use in the NHS as close as possible to it receiving its UK licence," said a spokesperson.

Mike Colley turned 80 in April. At his birthday party, he surprised his family by singing My Way in front of 40 guests. 

He told BBC News: "That's the confidence I have now. I'd never have done that even 12 months ago." 

His son Mark added: "I never thought I would see my dad so full of life again. It was an incredible moment."

Dr Emer MacSweeney, consultant neuroradiologist and medical director at Re:Cognition Health, led the trials of donanemab in the UK.

She said: "This is really significant and one of the biggest breakthroughs."

The Alzheimer's Society said: "This is truly a turning point in the fight against Alzheimer's and science is proving that it is possible to slow down the disease." 

Around 720,000 people in the UK might potentially benefit from these emerging new Alzheimer's disease treatments if they're approved for use, but the Alzheimer's Society said the NHS is "simply not ready to deliver them". 

Kate Lee, CEO for the charity, said: "Timely, accurate diagnosis is key, and currently only 2% of people in England and Wales receive their diagnosis through the specialist investigations needed to be eligible for these treatments.

"Alongside this, these emerging Alzheimer's disease drugs require regular infusions and monitoring, and the NHS is not yet equipped to do this at scale."

Also read NPR news：

https://www.npr.org/sections/health-shots/2023/07/17/1188075646/donanemab-experimental-alzheimers-drug-outperforms-lecanemab-leqembi