Alzheimer's Study Sparks a New Round
In the long-running debate over just what causes Alzheimer’s disease, one side looks to have scored a victory with new results with an in-development drug. But there’s enough variation in the data to ensure that the squabbling factions of Alzheimer’s will have plenty to fight about.ISOPROPYLBENZYLAMINE
At issue is the so-called amyloid hypothesis, a decades-old theory claiming that Alzheimer’s gradual degradation of the brain is caused by the accumulation of sticky plaques. And the new drug is BAN2401, designed by Biogen and Eisai to prevent those amyloid plaques from clustering and attack the clumps that already have.
In data presented last week, one group of patients receiving BAN2401 saw their amyloid levels plummet, a result that was tied to a significant reduction in cognitive decline compared with placebo.
To the amyloid-inclined, like Dr. Howard Fillit of the Alzheimer’s Drug Discovery Foundation, that marks a clear affirmation of the linkage between plaques and mental fortitude.
“I mean if you asked me five or 10 years ago if we’re going to have a drug that can remove the plaques from the brain, I would have thought this was space technology,” Fillit said. “And there was definitely a signal, in my opinion, on clinical outcomes, which is what we’ve all been looking for.”
But to skeptics, the trial was laden with confounding details that make it impossible to draw conclusions.
“These results are a mess,” wrote Baird biotech analyst Brian Skorney. “Not so much that they indicate an outright failure of the [amyloid] hypothesis, but they don’t really say anything informative at all.”
In the trial, every single tested dose had a significant effect on plaques as measured by a brain scan, and the more BAN2401 patients got, the less amyloid they had after 18 months. But looking at cognition, only the highest tested dose was significantly better than placebo at slowing down mental decline. And some of the patients who received lower doses actually declined faster than those who received no treatment at all.
If amyloid really is the driving factor behind Alzheimer’s, why didn’t each incremental reduction in plaques lead to a corresponding improvement in cognition?
Dr. Al Sandrock, Biogen’s chief scientific officer, said there is likely a threshold of amyloid reduction that must be reached before patients actually benefit. The low doses, despite their effect on plaques, might not have hit that threshold, Sandrock said, thus accounting for their poor performance on cognitive decline.
The divergence in the two curves is what gives Dr. Reisa Sperling, who was overall encouraged by the results, “the most pause.” But Sperling, director Center for Alzheimer Research and Treatment at Brigham and Women’s Hospital, noted that some of the study’s arms had small numbers of patients, making it difficult to draw conclusions. She said while there is a biological argument that could underpin the threshold hypothesis, she wanted to see more data from a larger trial with a more traditional design.