It has been a brutal year in the search for a treatment for Alzheimer's — here's where researchers …

brainAP/Alastair Grant

The search for an Alzheimer’s disease treatment has been
unsuccessful for the past 14 years. 

The latest failure came in September, when Axovant said it failed
a key late-stage trial for its drug, intepirdine. 

Alzheimer’s affects more than 5 million Americans, a
number that’s expected to balloon

13.8 million by

. There are only four drugs
that have been approved to treat the symptoms of the disease, and
the most recent drug approval happened in 2003.

2017 in particular has been a
tough year
for Alzheimer’s failures. In February alone,

 discontinued two of its trials, Merck
discontinued one of its studies, and Accera
failed a late-stage trial
 as well. Axovant’s trial
results are the last major results to come out in 2017, with the
next ones reading out in 2018 and a major wave of results
expected in 2019. 

Starting earlier

Research has determined that years — even decades — before a
person might start showing symptoms, amyloid beta deposits in the
brain that are characteristic of Alzheimer’s
disease can
start to accumulate
. By the time we start seeing
symptoms of dementia, researchers think, it might already be too
late to do much.

So preventing any progression at that stage is something
researchers are pinning a lot of hope on. There’s one
research effort going
on in Colombia
 that’s testing out an amyloid-related
drug in an extended family with a rare genetic mutation that
leads to early-onset Alzheimer’s. That study is in people who are
still considered cognitively healthy, so if the drug is able to
prevent cognitive decline, it could be a breakthrough.

What’s ahead

According to PhRMA, there are more than a dozen experimental
treatments that are still in
phase 3
, the latest stage of clinical trials before companies
present their data to the FDA. Here are some of the ones to look
out for in the next year or two. 

  • VTV Therapeutics, a small company in
    North Carolina, has an Alzheimer’s drug in late-stage
    trials called azeliragon that inhibits the RAGE
    , ideally helping people with mild Alzheimer’s
    delay cognitive decline. Its phase 3 trial is expected to wrap
    up in early 2018. The company got encouraging phase 2 results
    on the drug, which has been in the works for about 17 years.
    Even so, there’s no guarantee it will succeed. “We are doing a sound and rigorous
    experiment,” Dr. Larry Altstiel, VTV’s chief medical
    officer told Business Insider. 
  • Biogen’s aducamumab, a BACE
    is going after
    the amyloid
    ,” or the idea that targeting beta amyloid
    deposits in the brain to clear them out is the way to go
    about treating the disease. It’s expected to have results in
    2019 or early 2020.  
  • Lanabecestat, AstraZeneca’s BACE
    inhibitor, is going be reading out in 2019. Like
    Biogen, it’s going after the amyloid hypothesis. 
  • Eli Lily’s solanezumab
    failed a phase 3 trial
    in patients with mild dementia
    in November 2016, but has plans to keep trying the drug in
    pre-clinical stages of the disease to see if it works
    preventatively. Solanezumab is going after the amyloid
    hypothesis as well. While three trials have been disconnected,
    the fourth in this preventive setting is expected to have
    results in 2022. 
  • In February,
    drugmaker Merck
    stopped its
    late-stage trial of verubecestat in patients with mild to
    moderate Alzheimer’s, after a committee found that there was
    “virtually no chance of finding a positive clinical
    effect.” The hope was to have the drug — a BACE inhibitor
    — stop the disease from progressing. Merck said it’s still
    working on another late-stage trial for the drug to treat
    people with even earlier stages of the disease, and those
    results are expected in 2019. 
  • Genentech has two Alzheimer’s drugs
    in late-stage development, despite hitting
    setbacks. In February, Genentech and its partner AC Immune
    launched a phase 3 trial for crenezumab,
    another drug that’s targeting amyloid deposits in the brain.
    It’s expected to have data in 2020. The other is gantenerumab,
    a drug also targeting amyloid that failed earlier trials. The
    hope is that by
    increasing the dose
    , it might work. Genentech started a new
    phase 3 trial for gantenerumab in 2017. 

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