16 Time November 11, 2019
TheBrief Health
How a discontinued
Alzheimer’s drug
study got a second life
By Alice Park
△
Peter Wooding,
with wife JoAnn,
volunteered for
the Alzheimer’s
drug study
that was
discontinued
in MarchHow could two different reviews
of the data lead to such startlingly
different conclusions? “As a scientist,
I was completely confused,” says
Samantha Budd Haeber lein, head of
Biogen’s late-stage clinical development
for Alzheimer’s. “How could it be, when
we had such clear data from the [early]
clinical trial, such compelling data? The
scientist in me was really irritated—
what the hell happened?”When she and a team of statisticians
and programmers looked at the entirety
of the data, one of the studies showed
a clearly positive trend in reducing
cognitive decline, while the other did
not show much change in cognitive
functions at all. The two studies were
identical in terms of the types of patients
enrolled and how they were randomly
assigned to receive aducanumab or the“my firsT reacTion was To be angry,” says Joann
Wooding. “I’ve gotten over that, and frustration is more the
word right now.” Wooding’s husband Peter, who was diagnosed
with Alz heimer’s in 2016, was among the more than 3,
people with the disease who volunteered to test a promising
drug called aducanumab. In earlier study results released
the same year, the drug, developed by Biogen, a U.S. biotech
company, and Eisai, a Japanese pharmaceutical manufacturer,
seemed to accomplish a number of firsts for people with Alz-
heimer’s. It appeared to shrink deposits of the protein amyloid
accumulating in the brains of patients and, perhaps more
important, also slow the cognitive decline resulting from their
buildup. No drug for the disease had shown such dramatic
effects before. The study in which Peter was participating
was one of two follow-up trials designed to confirm that early
promise and, patients and doctors hoped, lead to the first
approved treatment that could actually slow the progression of
the neurodegenerative disease.
But last March, Biogen, after an early review of its data
involving half the patients, decided the results were not
promising enough to continue exposing patients to possible
side effects and terminated the trial. Peter and the other
volunteers stopped receiving infusions, and the company
began a more in-depth analysis.
The resulting full report, which included all 3,
patients, revealed a rosier picture. After 18 months of taking
aducanumab, people in one of the studies showed anywhere
from 15% to 27% less cognitive decline, as measured by
standard tests of memory and cognitive ability, compared
with those receiving a placebo. The cognitive protection was
most pronounced in those getting the highest dose of the
drug. On the basis of these results, the company plans to ask
the Food and Drug Administration to approve aducanumab
for the treatment of early Alzheimer’s disease.
“In retrospect, the... analysis [last spring] was incorrect,”
says Dr. Alfred Sandrock, chief medical officer at Biogen. “But
based on the data we had at the time, we followed the science
and made the decision to terminate the studies. With the
additional data and the additional analysis, we now know the
drug has efficacy.” The news is bittersweet for the Woodings,
who feel they have lost precious time in holding off the
disease ravaging Peter’s brain. After being randomly assigned
to receive either aducanumab or a placebo once a month for
18 months, all the volunteers were then given the opportunity
to receive the drug for at least two years. Peter had completed
his 18-month test period and had received his fifth infusion of
the active drug when Biogen pulled the plug.
“When he was off the drug, there were some changes, with
his short-term memory being the most affected,” says JoAnn.
“Over time I could see a difference without the drug.”