Much has been made of the recent advances in the treatment of Alzheimer’s disease. Three drugs have been approved for use by America’s Food and Drug Administration (FDA) in the past three years alone.
But just how much of a difference will these drugs make to Alzheimer’s sufferers? Are they going to be the game changers some have declared? The answer in at least one case appears to be no. The three drugs all go by similar names: aducanumab, donanemab and lecanemab. The suffix ‘-mab’ derives from what each of these drugs is, in scientific terms: monoclonal antibodies.
Let’s take a look at the three drugs in turn.
Alzheimer’s treatment #1: aducanumab
The first of the three to go through Phase III trials (in 2015), aducanumab initially demonstrated little if any benefit. By 2019, its manufacturer, Biogen, halted the trials. Months later, though, Biogen did an about face, claiming a new longer-term outcome analysis indicated that aducanumab slowed cognitive decline.
This prompted an application for FDA approval in 2020. In a surprise move, the FDA granted approval in 2021, going against the recommendation of its own advisory panel. In granting approval, the FDA said aducanumab was “reasonably likely to predict a clinical benefit to patients”.
Many experts disputed this, however. Making the decision more controversial, aducanumab produced serious side-effects in about 40 per cent of trial participants. A US government investigation into the approval process followed, generating further doubts.
Earlier this year, Biogen announced it would cease manufacturing aducanumab, citing a decision to “reprioritise its resources in Alzheimer’s disease”.
Ultimately, this was something of a ‘strike one’ for the monoclonal antibodies. But better news was to follow for donanemab and lecanemab. When translated to a commonly used 18-point cognitive scale it showed a difference of half a point.
Treatment #2: lecanemab
Manufactured by the Japanese company Eisai, lecanemab was clinically trialled in 2022, taking in nearly 1800 participants. All of them had early-stage Alzheimer’s disease and amyloid plaques (fatty protein build-ups in the brain believed responsible for the disease).
The trial showed those who took lecanemab had a 27 per cent slower rate of cognitive decline after 18 months compared with those given a placebo.
As small as that seems, it meant meaningful change for the participants. Further studies showed that the decline in quality of life slowed by about 50 per cent in people taking lecanemab versus those taking a placebo.
For lecanemab and those to whom it is prescribed, the future looks brighter than it otherwise might have been.
Alzheimer’s treatment #3: donanemab
After the promising 2022 trial of lecanemab, a 2023 study of donanemab, made in the USA by Lilly came next. This trial involved more than 1700 people, also with early stage Alzheimer’s disease.
The donanemab results showed an even greater slowing of cognitive decline than lecanemab, at almost 30 per cent.
Apples and oranges
No trials directly comparing lecanemab with donanemab have taken place as yet. If and when they do, allowances will have to be made for a significant difference between the two. While both donanemab and lecanemab clear plaques, lecanemab also targets amyloid proteins that haven’t accumulated yet. Donanemab does not.
Donanemab and lecanemab are not without side-effects, but both are showing great promise in slowing cognitive decline. Are they game changers? According to James Noble, a specialist in ageing and dementia at Columbia University in New York, yes, they are. But Dr Noble does add a caveat. “These aren’t perfect drugs. They aren’t a cure,” he said.
How, then, are they Alzheimer’s game changers? “They’ve given us hope in making an impact on the disease in ways that we’d never really had before.”
How would you feel about being part of a dementia drug trial? What concerns would you have? Let us know via the comments section below.
Also read: Lewy body dementia and its prognosis
Disclaimer: This article contains general information about health issues and is not advice. For health advice, consult your medical practitioner.
