* New drug blocks production of Alzheimer's-related proteins
* Lilly seen as front runner, but Merck trial could give
* Merck shares up about 0.5 pct
(Adds Lilly comment on its rival drug)
By Ransdell Pierson and Debra Sherman
Dec 3 Merck & Co Inc has moved to the
forefront of Alzheimer's disease research by starting a
mid-stage study of a drug from a new class of oral medicines
that aim to shut down production of a protein associated with
the memory-robbing disease.
The drugmaker said on Monday it had started the trial to
evaluate the safety and effectiveness of its so-called BACE
inhibitor, named MK-8931, in patients with mild-to-moderate
The Phase II trial, which will compare the drug with a
placebo, is a global, multi-center study that includes a group
of 200 patients to test safety. The study is expected eventually
to enroll up to 1,700 patients in the main Phase III trial.
Darryle Schoepp, head of neuroscience at Merck, said
drugmakers have been trying for a decade to develop treatments
that arrest Alzheimer's disease by blocking beta secretase, an
enzyme involved in production of toxic beta amyloid proteins
that form plaque in the brain believed to be a contributor to
By blocking beta secretase in earlier Phase I trials, the
Merck drug slashed by more than 90 percent the levels of beta
amyloid protein circulating in cerebrospinal fluid.
"It's like shutting the faucet so nothing comes out,"
Schoepp said in an interview. Merck hopes that by preventing
production of beta amyloid - the main component of brain plaque
- its drug will prevent a worsening of symptoms among patients
with mild-to-moderate stages of the disease.
Should the Merck drug prove safe in the Phase II safety
trials, Schoepp said the medicine could eventually be tested in
"prodromal" patients, or those with the very earliest signs of
Alzheimer's. They would include people with very mild memory
problems who have also been shown by blood tests or brain scans
to have worrisome initial buildup of amyloid plaque or who have
other "bio markers" associated with the progressive
A successful Alzheimer's treatment could reap billions of
dollars in annual sales. But many experts believe treatment must
be delivered before patients show signs of dementia because once
that happens, brain damage may be irreversible.
U.S. drugmaker Eli Lilly is also testing a beta secretase
inhibitor, as well as another experimental drug called
solanezumab that has shown hints of effectiveness in Phase III
studies. Solanezumab also targets beta amyloid protein, but
through a different mechanism than beta secretase blockers.
"In addition to solanezumab, which is currently in Phase III
clinical development, in July 2012 Lilly advanced our homegrown
beta secretase inhibitor into Phase II clinical development for
its potential to slow the progression of this devastating
disease," a Lilly spokesperson said.
Schoepp noted that the Merck drug is a pill, whereas
solanezumab is given by intravenous infusion. He added that
solanezumab is believed to work by removing some plaque already
deposited in the brain, whereas beta secretase inhibitors
directly interfere with production of the beta amyloid proteins
that form the plaque.
"Our drug attacks the amyloid pathway directly. We're
preventing it at the beginning. You can't get plaque if you
don't make these" protein fragments, he said.
Lilly is considered ahead of the its rivals in Alzheimer's
research after solanezumab, in Phase III trials, was shown in
August to slow cognitive declines in patients with mild symptoms
of the disease. However, the drug failed its overall goal of
delaying cognitive and physical decline in patients with
The start of Merck's new trial of MK-8931 could put the
company on an equal footing with Lilly in the race for the first
approved drug to delay progress of the disease.
Merck's drug appears almost to entirely prevent the
formation of new beta amyloid, the toxic proteins that lead to
plaques in the brain, while the Lilly drug acts by removing
existing plaques, according to Mark Schoenebaum, an analyst with
"We do not believe that Merck has any clinical efficacy data
at this point upon which it is basing its Phase II/III 'go'
decision. Thus, one must still view the Phase III as highly
speculative," Schoenebaum wrote in a research note.
Assuming the U.S. Food and Drug Administration asks Lilly to
conduct another confirmatory Phase III trial on its drug, the
Merck drug is on roughly the same timeline to potential approval
as the Lilly drug, he said.
If the FDA approves the Lilly drug on its existing data,
something Schoenebaum thinks is unlikely, then Lilly would be
about three years ahead, he added.
Merck shares were up 20 cents, or 0.45 percent at $44.50 in
afternoon trading on the New York Stock Exchange, while Lilly
shares were down 10 cents at $48.94.
Earlier this year, Roche Holding AG more than
doubled the size of a clinical trial of its experimental
Alzheimer's drug, gantenerumab, in patients who have early
Alzheimer's but have not yet developed dementia, putting it in
the vanguard of attempts to catch the disease in early stages.
(Reporting by Debra Sherman in Chicago and Ransdell Pierson in
New York; editing by Gerald E. McCormick, John Wallace, Matthew
Lewis and Dan Grebler)