By Peter Loftus And Shirley S. Wang
WASHINGTON--People with mild Alzheimer's disease who started
taking an experimental Eli Lilly & Co. drug earlier in the
course of their disease fared better than patients who started
later in a clinical trial.
The outcome may bolster the case among investors that the drug,
solanezumab, can slow the decline of memory and function in mild
Alzheimer's patients, despite prior studies with negative results.
But the new data aren't final proof of the drug's benefit--a
separate, continuing study due to end in late 2016 is designed to
more definitively test its efficacy and safety.
In another study, researchers said Biogen Inc.'s experimental
Alzheimer's drug reduced the volume of a substance in the brains of
patients that is believed to contribute to the disease. Results of
both studies are due to be presented Wednesday at the Alzheimer's
Association International Conference in Washington.
Lilly hopes solanezumab becomes the first marketed treatment to
slow the worsening of the underlying disease. Current treatments
for Alzheimer's can alleviate symptoms but don't slow underlying
disease progression. Jefferies & Co. analyst Jeffrey Holford
estimates the Lilly drug could generate peak annual sales of more
than $3 billion world-wide if it is approved for marketing by
regulators.
A leading theory in Alzheimer's research is that the buildup of
a sticky protein known as beta amyloid in the brain contributes to
the disease. Lilly's solanezumab is designed to bind to amyloid and
clear it from the brain. It is an antibody that is infused
intravenously.
But the amyloid hypothesis hasn't been proven in clinical
trials. In two large clinical trials reported in 2012, solanezumab
failed to significantly slow the decline of cognition and
functional abilities among the overall population of patients with
mild to moderate Alzheimer's, compared with a placebo. Other
companies' drugs targeting amyloid also have failed in trials.
Lilly scientists, however, said the drug appeared to slow
cognitive decline in a subgroup: patients with a mild form of the
disease. The company has continued developing the drug in mild
Alzheimer's patients.
Since 2012, Lilly has continued to provide the drug to patients
who received it in the earlier trials, and the company allowed
patients who originally received a placebo in those studies to
switch over to solanezumab. On average, the placebo patients
started solanezumab 18 months after the earlier patients.
Researchers tracked outcomes for both patient groups.
The new results showed that the patients who started therapy
earlier retained an advantage in cognition and daily function over
those who started later, and that this difference persisted for two
years. Researchers said such a finding is consistent with the
hypothesis that solanezumab is modifying the underlying disease. If
the study had found no significant difference between the early and
late starters, it would have indicated that solanezumab was merely
easing symptoms.
"Here we have a safe antibody treatment, solanezumab, that
appears to benefit mild Alzheimer's disease dementia subjects,"
said Paul Aisen, director of the Alzheimer's Therapeutic Research
Institute at the University of Southern California, who presented
the results. "And that benefit appears to reflect disease
modification."
Eric Siemers, an Alzheimer's researcher at Lilly, said the new
clinical data increases his confidence in solanezumab but "we'll
find out if it works or not" when a separate, continuing study of
the drug is completed by the end of 2016. The study of about 2,100
patients with mild Alzheimer's disease is comparing solanezumab
with a placebo, and its outcome will determine whether Lilly
submits the drug for marketing approval in the U.S. and
elsewhere.
In March, Biogen, a Cambridge, Mass.-based biotechnology
company, announced some results from an early-stage clinical trial
that showed its drug, aducanumab, given to a very small group of
participants with mild memory problems appeared to reduce the
amount of amyloid in the brain.
The treatment also appeared to slowed down cognitive
decline--particularly at the highest dose of 10 mg/kg--in these
people. The results impressed Wall Street and lifted the company's
stock to all-time highs. RBC Capital Markets analyst Michael Yee
estimates annual sales of the Biogen drug could top $10 billion if
it reaches the market.
The March findings, however, didn't include all doses of
medication at the 12-month time point.
Aducanumab is an antibody that is thought to bind to sticky
clumps of the protein amyloid, one of the hallmarks of the disease,
in the brain and causes cells to digest away the plaque and reduce
amyloid, said Al Sandrock, Biogen's chief medical officer.
On Wednesday, researchers will present Biogen's full one-year
data of all four medication doses at one year of treatment, as well
as more participants in the placebo arm of the study.
The results were largely consistent with the March analyses. The
findings show that the 6 mg/kg dose--its effect at 12 months hasn't
been announced previously--generally performed better than the 3
mg/kg dose but worse than the 10 mg/kg dose, exhibiting an expected
dose-dependent effect.
Write to Peter Loftus at peter.loftus@wsj.com and Shirley S.
Wang at shirley.wang@wsj.com
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