Researchers return to Alzheimer's vaccines, buoyed by recent drug
success
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[November 20, 2023]
By Julie Steenhuysen
CHICAGO (Reuters) - Breakthrough Alzheimer’s treatments that remove
toxic proteins from the brain have revived interest in vaccines to treat
the memory-robbing disease, potentially offering a cheaper,
easy-to-administer option for millions of people, according to
interviews with 10 scientists and company executives.
Clinical trials are underway or completed for at least seven Alzheimer’s
vaccines designed to harness the immune system to rid the brain of the
disease-related proteins beta amyloid or tau, a review of the U.S.
government’s ClinicalTrials.gov database found. More are on the way.
The renewed interest in Alzheimer's vaccines follows a promising first
attempt more than 20 years ago that was abandoned after 6% of study
volunteers developed life-threatening brain inflammation known as
meningoencephalitis.
Researchers then pivoted to a safer route, infusing highly targeted
man-made antibodies into patients that sidestep the body’s immune
machinery.
Eisai and Biogen's newly launched Leqembi and Eli Lilly's donanemab, now
under U.S. regulatory review, are two such treatments that cemented the
view that removing amyloid is key to fighting Alzheimer’s in people with
early-stage disease. That success followed years of failures that left
many experts questioning the amyloid theory.
Scientists, including those at Vaxxinity, AC Immune and Prothena,
believe they now understand what went wrong with the first vaccine and
are testing shots they hope will provoke an immune response without
causing excess inflammation. The U.S. Food and Drug Administration has
given the first two fast-track status, which should speed review of
those vaccines.
Dr. Reisa Sperling, an Alzheimer's researcher at Mass General Brigham in
Boston, said she believes vaccines will play an important role as
researchers look to prevent Alzheimer's. “I'm very keen that that's
where we need to go.”
Sperling is leading a trial in cognitively normal people with
Alzheimer's proteins in their brain. She is considering vaccines for her
next study in asymptomatic people with Alzheimer's proteins in their
blood, but not enough to register on brain scans.
Alzheimer's vaccines are still in the early stages and will require
large, years-long trials to show they work.
Still, a vaccine given quarterly or twice a year could offer a respite
from Leqembi’s expensive twice-monthly infusions, expanding access among
the estimated 39 million people globally with Alzheimer’s.
"They could be worldwide, and not that expensive," said Dr. Walter
Koroshetz, director of the neurological disorders division of U.S.
National Institutes of Health.
'THE GATES HAVE OPENED'
Vaxxinity may be furthest along, having already completed a small Phase
2 trial of its vaccine, UB-311. Chief Executive Mei Mei Hu said
Leqembi’s success validated a long questioned hypothesis.
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A doctor points out evidence of Alzheimer's disease on PET scans at
the Center for Alzheimer Research and Treatment (CART) at Brigham
And Women's Hospital in Boston, Massachusetts, U.S., March 30, 2023.
REUTERS/Brian Snyder/File photo
"What we know is that if we knock
out certain bad forms of amyloid, we will see an effect in clinical
outcomes, and that's amazing," she said of Leqembi's ability to slow
cognitive decline.
Data from Vaxxinity's Phase 2a trial of 43
volunteers in Taiwan published in August showed the vaccine was safe
and tolerable after 78 weeks, with almost all participants producing
an antibody response. There were no cases of brain swelling, but 14%
(6) developed brain bleeding, a side effect also common to the
infused treatments.
Vaxxinity has been seeking a partner to help fund a larger,
confirmatory trial, but found the climate over the past few years
"quite frigid," Hu said. “With (Leqembi’s) approval, the gates have
opened, and there's a lot more enthusiasm, a lot more investment."
WHAT WENT WRONG
The first Alzheimer's vaccine demonstrated signs of benefit, but
also triggered an out-of-control response from the immune system's
T-cells, which are only supposed to destroy infected cells.
Most of the newer vaccines target B cells, immune cells that produce
antibodies. AC Immune's vaccine only activates B cells, said Dr.
Michael Rafii of the University of Southern California. In a Phase 1
trial led by Rafii, the AC vaccine did not cause any
meningoencephalitis, but only a subset of participants developed an
immune response. The company is now testing a reformulated version.
AC Immune CEO Andrea Pfiefer suggested that the sustained immune
response to its vaccine in some patients explains the lack of brain
swelling or bleeding seen with monoclonal antibodies like Leqembi,
which peaks after each infusion. More data is expected in the first
half of 2024. AC is also collaborating with Johnson & Johnson on a
vaccine that targets tau, a toxic Alzheimer's protein associated
with brain cell death. Prothena, which was spun out a decade ago
from a company that co-developed that first vaccine, next year hopes
to begin a trial of a vaccine that targets both amyloid beta and tau
with the aim of Alzheimer's prevention.
Prothena also has an anti-amyloid antibody in Phase 1 trials and an
anti-tau antibody licensed to Bristol Myers Squibb.
Prothena CEO Gene Kinney said the company's vaccine produces high
levels of mature antibodies. Generating a strong immune response is
critical for such vaccines, which would typically be given to older
individuals with weaker immune systems, he said.
He sees vaccines as ideal for people with pre-symptomatic
Alzheimer’s. “What you want to do is prevent the disease from
occurring in the first place.”
(Reporting by Julie Steenhuysen; Editing by Caroline Humer and Bill
Berkrot)
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