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 company's case 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 other studies, Biogen Inc. announced some new data suggesting
that its experimental Alzheimer's drug slowed the progression of
the disease while researchers said a now-halted clinical trial of a
Roche Holding AG compound indicated the therapy reduced the volume
of a substance in the brains of patients that is believed to
contribute to the disease.
Results of these studies are due to be presented Wednesday at
the Alzheimer's Association International Conference in Washington.
The data are largely incremental but were still being watched
keenly by investors, who are looking for signals of potential
success after years of failed drug candidates in the Alzheimer's
space.
The drug industry trade group, the Pharmaceutical Research and
Manufacturers Association, recently released a report calculating
that 123 experimental therapies for Alzheimer's failed between 1998
and 2014 while only four drugs made it to market.
While analysts considered the new data positive and largely
expected for Lilly and Biogen, their shares were down in morning
trading. Some cautioned that the magnitude of the effect for
Lilly's compound looked modest.
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 Alfred 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.
"I breathed a huge sigh of relief" after seeing the Biogen data,
said Mark Schoenebaum, biotech and pharmaceuticals analyst at
Evercore ISI.
With a Roche compound called gantenerumab, new results in a
subset of participants of the biomarker and brain imaging data
nearly two years out showed that the compound did appear to reduce
amyloid plaque as hypothesized.
A trial of the therapy was terminated in December 2014 after a
preplanned look at the data in the middle of the study suggested
the treatment wasn't making an impact on cognition.
That means the compound does appear to do what it is theorized
to do, yet still didn't appear to influence cognitive decline,
raising questions about whether removing amyloid plaque yields a
benefit on cognition.
Philip Scheltens, Director of the Alzheimer Center at the VU
University Medical Center in Amsterdam, who presented the data to
media, said the findings suggested the doses tested were too low to
be effective.
Write to Peter Loftus at peter.loftus@wsj.com and Shirley S.
Wang at shirley.wang@wsj.com
Access Investor Kit for Roche Holding AG
Visit
http://www.companyspotlight.com/partner?cp_code=P479&isin=CH0012032048
Access Investor Kit for Roche Holding AG
Visit
http://www.companyspotlight.com/partner?cp_code=P479&isin=CH0012032113
Access Investor Kit for Biogen Idec, Inc.
Visit
http://www.companyspotlight.com/partner?cp_code=P479&isin=US09062X1037
Access Investor Kit for Eli Lilly & Co.
Visit
http://www.companyspotlight.com/partner?cp_code=P479&isin=US5324571083
Access Investor Kit for Roche Holding AG
Visit
http://www.companyspotlight.com/partner?cp_code=P479&isin=US7711951043
Subscribe to WSJ: http://online.wsj.com?mod=djnwires