Focus: Researchers return to Alzheimer's vaccines, buoyed by recent drug success

AC Immune SA

20/11/2023 11:00

By Julie Steenhuysen
       CHICAGO, Nov 20 (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  4523.T  and Biogen's  BIIB.O  newly launched Leqembi
and Eli Lilly's  LLY.N  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  VAXX.O , AC Immune
 AIU.O  and Prothena  PRTA.O , 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.
    "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  JNJ.N  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
 BMY.N .
    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.”

    <^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
US FDA grants standard approval of Eisai/Biogen Alzheimer's drug
    urn:newsml:reuters.com:*:nL1N3863GM
Experimental drug works best for Alzheimer's patients treated as
early as possible     urn:newsml:reuters.com:*:nL1N39318A
FOCUS-Blood tests needed for widespread Alzheimer's diagnosis on
the way     urn:newsml:reuters.com:*:nL1N3BG1W2
Injected version of Eisai/Biogen Alzheimer's drug works as well
as IV Leqembi     urn:newsml:reuters.com:*:nL1N3BV3SW
    ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^>
 (Reporting by Julie Steenhuysen
Editing by Caroline Humer and Bill Berkrot)
 ((julie.steenhuysen@thomsonreuters.com; 312-408-8131; Reuters
Messaging: Julie.steenhuysen.reuters.com@reuters.net))