By Daniela Hernandez, Jeanne Whalen and Allison Prang
Efforts to find treatments for Alzheimer's disease suffered
blows in recent days, but many companies, scientists and investors
are still optimistic that they can find a way to treat the
memory-robbing disease, which affects roughly 5.5 million
Americans.
Axovant Sciences Ltd. on Monday shuttered development for a
once-promising Alzheimer's drug, an announcement that came days
after Pfizer Inc. said it was giving up on the space entirely.
"The mood is definitely negative on anything near-term, [but]
there continues to be interest in this space," said Mark Ginestro,
a principal for health-care and life sciences strategy at KPMG in
San Francisco. "It's too big of a market to ignore. People are
going to continue to go after it despite the roadblocks."
Roche Holding AG, Biogen Inc., Eli Lilly & Co. and others
are still developing therapies. Startups with neuroscience
pipelines, like Denali Therapeutics Inc. and Verge Genomics, are
attracting funding, and so are early-stage research projects.
During the fiscal year 2017, the National Institutes of Health
will have poured an estimated $1.35 billion into Alzheimer's
disease, almost triple its investment for fiscal year 2013. And
Pfizer said it had plans to establish a corporate venture fund
focused on neuroscience projects.
Sales of successful treatments for the disorder could amount to
billions of dollars as demand for therapies increase due to an
aging population. Analysts had predicted that annual sales for
Axovant's drug, known as intepirdine, could have topped $2
billion.
"It's too early to give up," said Paul Aisen, the director of
the University of Southern California's Alzheimer's Therapeutic
Research Institute in San Diego. "We're actually on the precipice
of major advances. I would not discount all the disappointments
over the years, but I believe we're in good shape."
The recent failures that have plagued the pharmaceutical
industry and brewed much frustration among investors have been the
result of a suboptimal approach to drug development, Dr. Aisen
said. For years, the industry has focused on dementia, which
happens at the latest stages of the disease, when reversing the
damage done to the brain is difficult, if not impossible, he
said.
Many of the drugs that have failed in large clinical trials have
targeted beta amyloid, the sticky plaque in the brains of
Alzheimer's patients that many scientists believe is a leading
cause of the disease. But attacking these plaques in the brain
didn't affect cognition.
Companies and researchers pursuing treatments are still pursuing
amyloid in many cases, but they are beginning to focus on treating
patients earlier in the disease process, before they show memory
deficits or cognitive decline. New neuroimaging technologies,
genetics and more sensitive cognitive tests are also helping
clinicians to better understand how the disease progresses, and to
potentially identify patients who could benefit from treatment
before cognitive symptoms appear.
In some cases, patients are identified based on genetic testing
that suggests they might be at a higher risk of developing the
disease. Others have amyloid plaques, but don't yet have cognitive
deficits.
Lilly's amyloid-targeted drug, solanezumab, failed to benefit
patients in several large and costly studies in patients with mild
to moderate disease. After the failure of one study in late 2016,
Lilly said it had spent nearly $1 billion on the experimental drug,
and about $3 billion total on Alzheimer's research over the past
three decades.
But Lilly continues to test solanezumab in other human studies,
including one funded by the U.S. government testing the drug in
at-risk patients who don't yet have outward signs of the
disease.
Merck & Co. last year stopped a clinical trial of an
experimental Alzheimer's drug, verubecestat, because it wasn't
helping patients with mild to moderate forms of the disease. The
drug, a BACE inhibitor, aimed to prevent an enzyme from producing
the sticky amyloid.
Merck said it would continue a separate study of verubecestat in
patients at an earlier stage of Alzheimer's known as prodromal.
Results from that study are expected in 2019.
"The question is, how early is early enough?" Roger Perlmutter,
Merck's head of research and development, said in an interview.
"None of this is easy...we recognize this is one of the hardest
drug-development areas," he said, adding, "we simply do not believe
it is acceptable to stand on the sidelines."
Biogen is currently testing another antibody that goes after
amyloid possibly by stimulating microglia, the brain's scavenger
cells, to chew up the plaques. In a recent study, higher doses of
the drug, known as aducanumab, cleared more plaques, but adverse
effects were more common. The drug slowed cognitive decline in
patients with early Alzheimer's. Some scientists say that the drug
could cause inflammation in the long-term, which would be
detrimental to brain health. Results for larger trials are expected
in 2020.
Merck and other companies have also focused attacks on a
different protein, tau, that forms twisted proteins in the brains
of Alzheimer's patients.
That approach suffered disappointment in 2016, when a closely
watched trial of a tau-targeted drug developed by TauRx
Pharmaceuticals Ltd. failed to improve patients' cognition or daily
functioning in a clinical trial.
Even if companies can figure out how to reach patients earlier
in the process, success may not be as simple as targeting one
protein or another, scientists say. Some believe an interaction
between beta amyloid and tau plays a central role in the disease.
Others think there are many possible triggers, including some
beyond beta amyloid or tau.
Combination therapies targeting several Alzheimer's-related
proteins, like amyloid and tau, could be more fruitful. Biogen and
Lilly said such multifaceted treatments are likely the future of
Alzheimer's therapeutics.
Axovant's drug, intepirdine, inhibited signaling pathways in the
brain. Scientists thought that it could help with cognitive
decline. Other attempts at developing similar drugs have also
failed.
Some companies are looking for treatments in the cutting-edge
field of gene therapy, which introduces beneficial genes to the
body to help fight disease.
Johnson & Johnson last week announced a collaboration with
the University of Pennsylvania aimed at inserting certain genes
into harmless viruses that would carry the genes to the cells. The
genes would then instruct the cells to secrete beneficial
antibodies that would fight Alzheimer's.
Once injected into the body, the viruses ideally would be able
to cross the blood-brain barrier, which separates brain tissue from
the rest of the body, Eric Schaeffer, senior director of
neuroscience innovation at Johnson & Johnson, said in an
interview. The research is at an early stage and could be four or
five years away from human studies, he said.
Denali Therapeutics, a San Francisco-based biotech company that
has multiple Alzheimer's treatments in its pipeline, went public
last month. The company has three Alzheimer's drugs in preclinical
development targeting tau and other mechanisms, according to its
website. Denali also announced last week it is working with Japan's
Takeda Pharmaceutical Co. to focus on neurodegenerative diseases
like Alzheimer's.
Given the huge unmet need in Alzheimer's, there are incentives
to try to make headway in the market, according to Ritu Baral,
senior biotech analyst for Cowen. Big pharmaceutical companies tend
to be more conservative, she said.
"Small to midcap biotechs are inherently [willing to be]
riskier," she said. "Everything is an investment for the
future."
--Peter Loftus contributed to this article.
Write to Daniela Hernandez at daniela.hernandez@wsj.com, Jeanne
Whalen at jeanne.whalen@wsj.com and Allison Prang at
allison.prang@wsj.com
(END) Dow Jones Newswires
January 08, 2018 19:42 ET (00:42 GMT)
Copyright (c) 2018 Dow Jones & Company, Inc.
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