- James Gallagher
- Health and science reporter
Licanimab is an antibody, which is designed to tell the immune system to clear amyloid from the brain
The announcement of the first drug effective in slowing brain damage as a result of dementia (Alzheimer’s disease) was greatly celebrated by the medical community, and considered it a historic and important moment.
This research advance is set to end decades of failure and show that a new era of drugs to treat Alzheimer’s disease, the most common form of dementia, is possible.
Despite this, the drug, called lecanimab, has only a small effect and its impact on people’s daily lives is still a matter of debate.
The drug works in the early stages of the disease, so most patients will not benefit from the new discovery unless methods of early diagnosis are developed.
Licanimab attacks the sticky substance called amyloid beta (amyloid beta peptide) that builds up in the brains of people with Alzheimer’s disease.
For a medical field riddled with failure, despair and disappointment, some see these trial results as a triumphant turning point.
Alzheimer’s Research UK confirmed the findings were “extremely significant”.
It is “historic” and encouraging, said Professor John Hardy, one of the world’s leading researchers behind the whole idea of targeting amyloid 30 years ago, “we are seeing the beginning of treatments for Alzheimer’s”.
Professor Tara Spears-Jones, from the University of Edinburgh, said the results were significant, “because we’ve had a 100% failure rate over a long period of time”.
Currently, Alzheimer’s patients get other medications to help manage their symptoms, but nothing changes the course of the disease.
Licanimab is an antibody, like one the body produces to attack viruses and bacteria, that is designed to tell the immune system to clear amyloid from the brain.
Amyloid is a protein that collects in the spaces between nerve cells in the brain and forms special plaques that are one of the hallmarks of Alzheimer’s disease.
The drug was tested on a large scale with the participation of 1,795 volunteers suffering from Alzheimer’s disease in its early stages. Lekanimab was given every two weeks.
The results were presented at the Alzheimer’s Clinical Trials Conference in San Francisco and published in the New England Journal of Medicine, but they are not a magic cure. The symptoms of the disease continued to deprive people of their mental capabilities, but this decline slowed by regarding a quarter over the course of 18 months of treatment.
The data is already being evaluated by US regulators, who will soon decide whether licanimab can be approved for wider use. The drug’s developers, Japan’s Eisai Corp. and US Biogen Pharmaceuticals, plan to get approval for the drug in other countries next year.
David Essam, 78, who was in Britain, took part in international trials of the drug.
Issam suffers from Alzheimer’s, and had to give up working as a carpenter, and he no longer remembers how to make a cupboard or use his tools. He now uses a digital watch because he can’t tell the time using a regular watch.
His wife Cheryl said: “He’s not the man he used to be, he needs help with most things, and his memory in general is almost nonexistent.” But she said the experience gave the family hope.
“If someone can slow down (Alzheimer’s disease) and eventually stop it, that would be great, because it’s just a bad disease,” Essam said.
There are more than 55 million people in the world like David Essam, and the number of people with Alzheimer’s disease is expected to exceed 139 million by 2050.
Will it make the difference?
There is debate among scientists and clinicians regarding the effect of licanimab in the “real world”.
The slowing of memory decline with the drug was monitored by ratings of the person’s symptoms. The experimenters set an 18-point scale, ranging from normal dementia to severe dementia. Those who received the drug were 0.45 points better off.
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The emergence of drugs that alter the course of disease raises big questions regarding whether health services are ready to use them
Prof Spiers-Jones said it had a “little effect” on the disease, but “although not significant, I would accept it”.
Dr Susan Koolhaas, of Alzheimer’s Research UK, said it was a “modest effect… but it gives us a little bit of a head start” and the next generation of drugs will be even better.
But there are also risks associated with the drug. Brain scans showed a risk of cerebral hemorrhage (17 percent of the participants) and brain swelling in 13 percent. Overall, 7 percent of people who took the drug had to stop because of side effects.
The crucial question is what will happen following 18 months of the experiment, and the answers are still speculation.
Dr Elizabeth Coulthard, who treats patients in North Bristol, says people have an average of six years of living independently once MCI sets in.
She added that working to slow this decline by a quarter might equate to an additional 19 months of independent life without the need for assistance, “but we don’t know that yet.”
It is even scientifically plausible that the effectiveness is greater in longer trials. “I don’t think we can assume that this will happen,” says Dr. Koolhaas.
The emergence of disease-altering drugs raises big questions regarding whether health services are ready to use them.
Medicines must be given early in the disease before significant brain damage occurs, while most people who are referred to memory services are in the later stages of the disease.
This requires people to apply for treatment as soon as they develop signs of memory problems and for doctors to be able to send them for amyloid tests, either with brain scans or spinal fluid analysis, to determine if they have Alzheimer’s disease or another form of dementia.
Currently, only 1 to 2 percent of people with dementia undergo such tests.
“There is a huge gap between current service delivery and what we need to do to deliver disease-modifying therapies,” said Dr. Elizabeth Coulthard.
For now, she added, only those who live near large medical centers or pay private money are likely to benefit.
The scientists also stressed that amyloid is just one part of the complex picture of Alzheimer’s disease and should not become the sole focus of treatments.
The immune system and inflammation are heavily involved in the disease, and another toxic protein called tau is found where brain cells are already dying.
“That’s where it’s worth it,” said Professor Spiers-Jones.
“I’m really excited that we’re on the cusp of understanding enough to get around the problem and we should have something that makes a bigger difference in a decade or so,” she added.
