By Denise Roland
Novartis AG thinks its best bet for testing two new Alzheimer's
drugs is on people who don't actually have Alzheimer's.
The Swiss drug giant is looking for people whose genes put them
at high risk of developing Alzheimer's, but who haven't yet fallen
victim to the mind-robbing disease. It hopes such early treatment
proves more successful than past efforts to tackle the disease once
it has taken hold.
The history of Alzheimer's research is marked by disappointment.
In November, a high-profile Eli Lilly & Co. drug called
solanezumab was the latest to fail a late-stage clinical trial.
That drug aimed to clear clumps of a protein called beta amyloid in
the brain, which are closely linked with Alzheimer's. So far, no
company has produced a drug that can delay the progression of
Alzheimer's.
One of the new Novartis drugs, known as CAD106, is designed to
boost the immune system's ability to clear beta amyloid from the
blood. The other, which Novartis is developing with Amgen Inc. and
is called CNP520, aims to stop its formation in the first
place.
"If an anti-amyloid strategy is going to work, the best way to
do so is with prevention," said Steven Arnold, a neurologist at
Massachusetts General Hospital in Boston.
Recruiting patients to receive treatment for a disease they
don't have -- and may never develop -- is riven with logistical and
ethical challenges.
The company is looking for people with two copies of a gene
called APOE4 to participate in its study. Having two copies of the
gene doesn't inevitably lead to Alzheimer's, but the roughly 2% of
people who fit this profile are around three times as likely to
develop dementia as the general population, according to a recent
analysis in the scientific journal PLOS Medicine.
The Banner Alzheimer's Institute, a Phoenix nonprofit, is
helping Novartis find eligible participants with a campaign
launched at the end of 2015 to test people for the APOE4 gene. The
institute places television and newspaper ads, does mass mailings
and runs events in clinics to publicize the program, called
Genematch.
So far, around 35,000 people have signed up, agreeing to send
swabs of their cheek cells for testing. "We seem to have tapped
into a very motivated group of people," said Pierre Tariot,
director of Banner. "Not surprisingly, a lot of them have a family
history of Alzheimer's."
Margaret, a 71-year-old from Virginia, discovered two weeks ago
that she has two copies of the APOE4 gene. She signed up for the
Genematch program earlier this year after hearing about it through
the hospital that is caring for her older sister, who has
Alzheimer's.
"It is shocking," said Margaret, who declined to give her last
name because she hasn't yet told her family. But "if this works and
can prevent or slow it down, then obviously I'd like to
participate. That part of it is a no-brainer."
Only a fraction those who sign up will be eligible for the
trial. As well as having two copies of the APOE4 gene, participants
in the Novartis study must be healthy, between the ages of 60 and
75, and have no outward signs of Alzheimer's, such as cognitive
decline. Fewer than 10% of the roughly 1,300 participants needed
for the trial have been recruited so far, Dr. Tariot said.
The Genematch staff doesn't know any individual participant's
genetic results. Instead, a computer program provides a list of
names -- only some of whom are genetic matches -- for them to call.
On that call, Genematch will tell the person they might be eligible
for a trial and tell them about nearby participating hospitals.
Participants are informed of their genetic profile -- usually by
a genetic counselor -- only after a lengthy assessment by staff at
the clinical-trial site to determine that they are eligible for,
and willing to enroll in, the study.
"The critical thing is that this is done in a highly ethical
way," said Vas Narasimhan, global head of drug development at
Novartis. "If a patient is not selected for the study, we are not
intervening to help them so there is no reason to provide them with
this information."
Later this year, Novartis plans to start a further trial that
will be open to people who have just one copy of the APOE4 gene,
Dr. Narasimhan said. Around a quarter of the population is thought
to fit this profile, and they are about 1 1/2 times as likely to
develop mild cognitive impairment or dementia as the general
population.
After the string of high-profile failures in amyloid-busting
drugs, experts are divided over whether they are the right approach
to tackling Alzheimer's. "The field is very pessimistic right now,"
said Murali Doraiswamy, director of the neurocognitive disorders
program at Duke University Health System in Durham, N.C.
But the Novartis study was among a small group of trials that
could still vindicate this approach, Dr. Doraiswamy said. "We've
learned a lot from previous [failed] trials," he said, adding that
the "elegant" design of the Novartis study -- in focusing on a
narrow band of people known to have heightened risk of Alzheimer's
-- makes it a "near-perfect model to test the amyloid thesis."
(END) Dow Jones Newswires
April 22, 2017 10:43 ET (14:43 GMT)
Copyright (c) 2017 Dow Jones & Company, Inc.
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