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.
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.
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
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