The long, discouraging go after medicine that works to treat Alzheimer’s reached a potentially promising milestone on Wednesday.
For the primary time during a large clinical test, a drug was ready to both reduce the plaques within the brains of patients and slow the progression of dementia.
More extensive trials are going to be needed to understand if the new drug is actually effective, but if the results, presented Wednesday at the Alzheimer’s Association International Conference in Chicago, are borne out, the drug could also be the primary to successfully attack both the brain changes and therefore the symptoms of Alzheimer’s.
“This trial shows you'll both clear plaque and alter cognition,” said Dr. Reisa
Sperling, director of the middle for Alzheimer Research and Treatment at Brigham and Women’s Hospital in Boston, who wasn't involved in the study.
“I don’t know that we’ve hit a home run yet. It’s important to not over-conclude the info. But as a symbol of concept, I desire this is often very encouraging.”
Aside from a couple of medicines that will slow memory decline for a few months, there's no effective treatment for Alzheimer’s, which affects about 44 million people worldwide, including 5.5 million Americans.
It's estimated that those numbers will triple by 2050.
The trial involved 856 patients from us, Europe and Japan with early symptoms of cognitive decline.
They were diagnosed with either mild cognitive impairment or mild Alzheimer’s dementia, and everyone had significant accumulations of the amyloid protein that clumps into plaques in people with the disease, said Dr. Lynn Kramer, chief medic of Eisai, A Japan-based company that developed the drug, referred to as BAN2401, alongside Biogen, based in Cambridge, Mass.
Many other drugs have managed to scale back amyloid levels but they didn't ease memory decline or other cognitive difficulties.
Within the data presented Wednesday, the very best of the five doses of the new drug — an injection every fortnight of 10 milligrams per kilogram of a patient’s weight — both reduced amyloid levels and slowed cognitive decline in comparison to patients who received a placebo.
Of the 161 patients within the group taking the very best dose, 81 percent showed such significant drops in amyloid levels that they “converted from amyloid positive to amyloid negative,” Dr. Kramer said in an interview, meaning that the patients’ amyloid levels dropped from being considered high enough to correlate to dementia to A level below that dementia threshold.
And on A battery of cognitive and functional tests measuring memory and skills like planning and reasoning, the performance of the high-dose group declined at a rate that was 30 percent slower than the speed of decline within the placebo group.
Dr. Sperling, who briefly advised Eisai last year on the special drug called the reductions in amyloid “dramatic,” but said the cognitive results were less momentous.
Still, she said, “If you'll really slow the decline by 30 percent for people that are still normal or very mildly impaired, that might be clinically important.”
Dr. Samuel Gandy, associate director of the Sinai Alzheimer’s Disease research facility said that for the drug to actually be effective, it might need to allow patients to function longer independently without having caregivers to assist them with basic daily activities.
That sort of the application wasn't reflected within the data presented Wednesday.
“I wouldn’t say this is often a quantum jump,” he said. “It maybe a convincing moving of the needle.
But it’s not clear that the needle has moved far enough to form a difference in people’s lives.”
Dr. Kramer said the results were statistically significant 18 months after patients began taking the drug, but improvement began to be noticed after about six months.
The 253 patients within the group receiving the second-highest dose also had amyloid and cognitive results that followed an identical trend.
In December 2017, the businesses reported that a statistical analysis of the trial at the 12-month mark projected that the drug wouldn't end in a statistically significant slowing of dementia.
That meant that the trial didn't meet its primary benchmark, which caused some experts and investors to voice skepticism about the drug.
The 18month results allayed a number of that skepticism, although the Alzheimer’s Association issued a press release expressing caution and saying the results were “not large enough to definitely demonstrate cognitive efficacy.”
The results came from a Phase 2 trial, which measures both the security and therefore the efficacy of a drug, but is usually considered an intermediate step to larger and more extensive Phase 3 trials.
Other drugs have shown promise in Phase 2, only to disappoint in Phase 3.
In this trial, patients were randomized into six groups, with 247 patients receiving placebo injections while the opposite five groups received varying doses of the drug.
One unusual aspect of the trial raised questions for a few experts.
Eisai and Biogen used a cognitive assessment they devised.
Called the Alzheimer’s Disease Composite Score (Adcoms), it draws on elements from three other, skilled cognitive tests.
Dr. Kramer said Adcoms was developed to compile the measures from those three tests that were sensitive enough to live change at such an early stage of dementia.
The info presented on Wednesday indicated that the patients also showed positive results on two of the three established tests when those were checked out separately.
Some potential Alzheimer’s treatments have resulted in serious side effects which will cause dangerous swelling or bleeding within the brain.
Fewer than 10 percent of the patients taking the new drug experienced such effects, the businesses reported, making it relatively safe.