For the first time in a Phase II clinical trial, mental decline in a group of Alzheimer’s patients was slowed by a third over a two year period.
This means that the participants’ ability to think and to care for themselves dropped at a significantly slower rate than patients given a placebo.
After six to 12 months of taking an experimental drug called donanemab, the patients’ brains appeared to be cleared of protein amyloid plaques.
The results were announced this week by the drug maker Eli Lilly which intends to submit the trial results for peer-review and is preparing for talks with the US Food and Drug Administration and “global regulators”. This would no doubt include Australia’s Therapeutic Drug Administration.
The full results of the small study will be presented at a future medical congress and submitted for publication in a peer-reviewed clinical journal.
Meanwhile, this is an ongoing trial for participants, affording researchers a longer view of its effect on patients.
If the trial results hold up in a bigger peer-reviewed study, the drug would represent a rare step toward bringing Alzheimer’s under some form of control.
For the moment, the language around Alzheimer’s treatment, from the Alzheimer’s Association, goes like this: “While there is no cure for Alzheimer’s disease or a way to stop or slow its progression, there are drug and non-drug options that may help treat symptoms.”
Big claims, big money
Dr Daniel Skovronsky, Lilly’s chief scientific officer, said in a prepared statement: “The positive results we have obtained today give us confidence in donanemab and support its rapid and deep plaque clearance for the potential treatment of Alzheimer’s disease.”
The announcement causing the company’s stock price to soar, with business analysts projecting the drug could earn the company US$5 billion a year.
In fact, oddly – given that researchers have been fruitlessly looking for a way to slow the rate of Alzheimer’s for at least 20 years – much of the media excitement was about how much money the drug could be worth.
How did the study work?
The two-year, phase 2 clinical trial included 272 patients with mild-to-moderate Alzheimer’s disease symptoms.
Half the patients received the drug – an investigational antibody that targets a modified form of beta amyloid called N3pGby – in an infusion every four weeks. The others received a placebo.
After six to 12 months of treatment with the drug, patients who received the drug no longer had amyloid protein plaques that are hallmarks of Alzheimer disease, said Dr Skovronsky.
Further, patients with “early symptomatic showed significant slowing of decline (32 per cent) in a composite measure of cognition and daily function in patients with early symptomatic Alzheimer’s disease.”
At this stage, the study has not been reviewed by other researchers and has not been published in any form.
About a third of patients experienced an accumulation of fluid in the brain, a common side effect in Alzheimer’s patients treated with monoclonal antibodies.
Doctors not involved in the study welcomed the results with the caveat they needed to be replicated in further trials.
Evidence of heading in the right direction
Monoclonal antibodies mimic the antibodies produced as part of your immune system’s response to foreign invaders or vaccines. The theory is that they may prevent beta-amyloid from clumping into plaques or remove accumulated beta-amyloid plaques from the brain.
The latest study supports that theory.
This isn’t the first time that Eli Lilly has trialled a monoclonal antibodies as a potential Alzheimer’s treatment. A 2018 paper published in the New England Journal of Medicine found that solanezumab, a monoclonal antibody developed by Eli Lilly that targets amyloid plaques, did not significantly slow cognitive decline.
Just last month, an independent advisory panel of the US Food and Drug Administration rejected approval of aducanumab, an injectable, monoclonal antibody produced by a company called Biogen.
The panel said the drug failed to demonstrate efficacy and more research is needed.
The previous week, Biogen’s stock price soared after FDA reviewers indicated they had in fact found convincing evidence that the drug worked. Patient groups lobbied for the drug to be approved.
Biogen – which pledged to continue working in concert with the FDA (meaning more trials) – welcomed the news from Eli Lilly, which is now seen as the great hope.
Analysts from the Mizuho Financial Group wrote:
“Our expert found the results fairly encouraging and sees a higher likelihood of success for donanemab relative to other antibodies at comparative stages of their development.
“However, given the disappointing history of the amyloid beta approach to date, our expert remained cautious in his outlook overall and believes donanemab’s probability of clinical success is still less than 50 per cent.”
In Alzheimer’s research, they are damn good odds.