A trial of a new drug to combat Alzheimer’s disease has produced encouraging results, slowing clinical decline by 35 percent and leading to a 40-percent reduction in patients losing the ability to carry out everyday tasks. Pharma giant Eli Lilly and Company is now moving towards securing regulatory approval for the drug, called donanemab.
It’s been a big couple of years in Alzheimer’s disease research. In 2021, the FDA approved the first drug in 18 years to treat the condition. Although there were still question marks over the drug’s ability to slow memory decline in patients, it was a welcome step forward. Since then, another drug, lecanemab, entered clinical trials with great fanfare; but news of a handful of deaths linked to the trial raised concerns about safety.
The latest drug, donanemab, targets the same pathological protein as these other agents: amyloid-beta. The field of Alzheimer’s research remains divided as to whether amyloid-beta or another pathological protein, phosphorylated tau, is the main driver of the disease. Current guidelines require clinicians to establish the presence of both amyloid plaques and tau tangles, as well as evidence of neuronal loss, in the brain before an Alzheimer’s diagnosis can be given.
A previous virtual clinical trial tested donanemab against the already approved aducanumab, and found that while both were efficient at clearing amyloid plaques, donanemab appeared to be slightly better at slowing cognitive decline.
Now, Lilly has released a statement detailing the results of a Phase 3 clinical trial in 1,182 Alzheimer’s patients.
After one year, 47 percent of the participants treated with donanemab showed no worsening of their disease, compared with 29 percent of participants taking a placebo. Those treated with the drug also showed 40 percent less decline in their ability to carry out daily tasks after 18 months, and had a 39 percent reduced risk of progressing to the next clinical stage of the disease.
“We are extremely pleased that donanemab yielded positive clinical results with compelling statistical significance for people with Alzheimer’s disease in this trial,” said Lilly’s chief scientific and medical officer, Daniel Skovronsky. “This is the first Phase 3 trial of any investigational medicine for Alzheimer’s disease to deliver 35% slowing of clinical and functional decline.”
Significantly fewer amyloid plaques could be observed in the brains of trial participants after taking the drug for only six months. “This study’s topline results provide compelling support for the relationship between amyloid plaque removal and a clinical benefit in people with this disease,” said Dr Eric Reiman, CEO of Banner Research, which was one of the research sites for the trial.
A second population of 552 people with more advanced disease – illustrated by higher levels of pathological tau protein – was also recruited for the trial. When these patients were combined with the original trial population, the results still showed a significant slowing of cognitive decline, although it’s likely these drugs will provide the most benefit for patients in the early stages of the disease.
As with all medical treatments, there is a risk of side effects. For Alzheimer’s treatments targeting amyloid plaques, a condition called amyloid-related imaging abnormalities (ARIA) can occur. There are two subtypes of ARIA, causing either areas of swelling or micro-bleeds in the brain. Thankfully, most cases in the trial were described as “mild to moderate”, but two participants in the trial died as a direct result of ARIA, as well as a third following a case of ARIA.
According to the president of the British Neuroscience Association Professor Tara Spires-Jones of the University of Edinburgh, who was not involved in the trial, the results sound “very promising”. But, she cautioned, “It is important to note that there were rare serious side effects of the treatment with brain swelling and small strokes that seem to have contributed to the death of 3 of the participants in the trial. Regulators will have to decide whether the benefits of treatment outweigh these risks.”
There’s no indication yet of how long the approval process may take, but Lilly says they will “work with the FDA and other global regulators to achieve the fastest path to traditional approvals.”
For now, though, the global Alzheimer’s research community is awaiting the complete dataset from the trial.
“The future for the treatment of Alzheimer’s disease is looking increasingly promising,” commented Professor Perminder Sachdev of UNSW Sydney, who was not involved in the trial. “Of course, we need the full data to evaluate it, and the rate of adverse effects is a concern, but I am heartened by the news.”
Source Link: New Alzheimer’s Drug Halts Disease Progression In 47 Percent Of Trial Patients After 1 Year