For the second time this year, a new drug showed that the cognitive decline caused by Alzheimer’s disease – the leading cause of dementia worldwide that affects an estimated 55 million people – can be slowed down.

Clinical trial results for donanemab, presented to the Alzheimer’s Association International Conference on Monday, showed the antibody medicine developed by Eli Lilly slowed the cognitive decline of Alzheimer’s patients by 35%. The drug was even more effective in the earliest stages of the disease, reducing cognitive decline in patients by around 60%.

Lecanemab, a similar drug made by Eisai and Biogen, received full marketing approval from the US Food and Drug Administration (FDA) earlier this month, based on clinical trial data that showed the drug slowed cognitive decline in participants by 27%. 

The back-to-back success of trials for antibody treatments targeted at Alzheimer’s are the culmination of decades of research long viewed as a dead-end. A decade ago, leading drugmakers such as GSK, AstraZeneca and Pfizer shelved efforts to develop drugs to treat the disease, citing the high price tag and slim chances of success. 

“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,” said Giles Hardingham, who leads the UK Dementia Research Institute. “It is terrific to see these results published.” 

The FDA approval of Lecanemab in June was the first time a drug proven to slow the effects of Alzheimer’s was made available to patients, marking a watershed moment in the fight against the disease. Eli Lilly said in a press release it expects the FDA to take regulatory action on donanemab by the end of this year. 

While the clinical effects of recent breakthrough drugs remain modest, experts said their efficacy proves that the once unstoppable disease could one day be managed and treated. 

“This is truly a turning point in the fight against Alzheimer’s,” said Dr Richard Oakley, an associate director of research and innovation at the Alzheimer’s Society. “Science is proving that it is possible to slow down the disease.”

Clinical results highlight the complexity of Alzheimer disease

An experimental drug from Eli Lilly works best if Alzheimer's patients are treated as early as possible, ideally before they develop symptoms of the brain-wasting disease, according to researchers https://t.co/6wSrv1HILN pic.twitter.com/uHtHHJF9GZ

— Reuters (@Reuters) July 17, 2023

Both new drugs are based on a theory of Alzheimer’s called the ‘amyloid cascade hypothesis’, which holds that the abnormal buildup of a small proteins in the brains of people with Alzheimer’s is a primary cause of the disease. 

The proteins, known as amyloid peptides, clump together to form plaques that can damage neurons and kill cells. Lecanemab and donanemab work by clearing these toxic proteins from the brains of patients.

Brain scans of patients participating in the clinical trials showed both drugs were extremely effective at eliminating the amyloid proteins they are designed to target. Donanemab was so effective that a significant number of patients were switched to a placebo after the drug cleared enough amyloid plaques. 

The trials show that removing amyloid from the brain is capable of changing the course of Alzheimer’s. But a series of editorials published in the Journal of the American Medical Association (JAMA) alongside the results for Eli Lilly’s drug said the data showed amyloids are just one part of the complex picture of Alzheimer’s. 

“Donanemab was very effective at eliminating its target,” Jennifer Manly, from Columbia University Irving Medical Center, and Kacie Deters, from the University of California, Los Angeles, wrote in one JAMA editorial. “The clinical effect was comparatively weak.”

In another editorial, a team of experts from the University of California, the University of Wisconsin and Upstate Medical University echoed similar concerns about the drug’s limitations, observing that the “results serve to highlight the complexity of Alzheimer disease itself.” 

“The exceptional ability of drugs such as donanemab and lecanemab to remove amyloid, paired with their rather subtle effect on the rate of decline in cognitive and functional measures, suggests that amyloid is likely not the only factor that contributes to Alzheimer’s disease progression,” they said. 

Both drugs also involve risks. Brain swelling was observed in up to a third of patients in the donanemab trial, mostly without incident. Brain bleeding occurred in a small minority of patients, and three participants, including one from the placebo group. died of “treatment-related” complications.

Then there is the price-tag: One year of Lecanemab costs $26,500 in the United States. The competition introduced by Eli Lilly’s new drug is expected to reduce the price, but cutting-edge treatments don’t become inexpensive overnight. 

“The modest benefits would likely not be questioned by patients, clinicians, or payers if amyloid antibodies were low risk, inexpensive, and simple to administer,” another JAMA editorial observed. “They are none of these.”

A ‘new era’ in the dementia fight

Science still has much to learn about Alzheimer’s, but the pace of research is picking up. More trials for Alzheimer’s drugs are ongoing now than ever before, according to research from the University of Nevada.

And there is a lot of ground to catch-up: Nearly 5 million papers about cancer have been published on the public medical research database PubMed – 19 times more than on dementia. Experts hope recent breakthroughs will stimulate funding and allow the field to build towards more effective medicines.

“This is just a start,” said Howard Fillit, chief scientist of the Alzheimer’s Drug Discovery Foundation. “We must continue advancing the drug pipeline to develop the next class of drugs centered around the biology of aging to ultimately stop Alzheimer’s in its tracks.

The new treatments for Alzheimer’s disease are not a cure, but they can still be life-changing. Slowing the onset of common symptoms like memory loss, concentration lapses, and difficulties communicating can allow people with Alzheimer’s to live active, independent lives for longer.

David Colley, an 80-year-old patient who took part in the clinical trial of the drug donanemab, told the BBC that he is “one of the luckiest people you’ll ever meet.”

His son, who observed Colley’s cognitive decline in the years leading up to the trial, said the treatment stabilized his father’s condition, allowing him to continue to participate in the family’s life.

“Thanks to decades of research, the outlook for dementia and its impacts on people and society is finally changing,” said Dr. Susan Kohlhaas, research director at Alzheimer’s Research UK. “We’re entering a new era where Alzheimer’s disease could become treatable.”