* Boosts HDL levels 128.8 pct at highest dose
* No safety problems seen with drug in Phase II study
* Company to begin Phase III trial "as soon as possible"
By Lewis Krauskopf and Bill Berkrot
ORLANDO, Fla., Nov 15 An experimental heart
drug from Eli Lilly and Co dramatically boosted levels
of "good" cholesterol and appeared to be safe, according to
data from a clinical trial, providing new hope for a class of
medicines with a troubled past.
The drug, evacetrapib, increased HDL cholesterol by 53.6
percent at the lowest dose and by a whopping 128.8 percent at
the highest dose in the mid-stage study, according to the data,
presented at the American Heart Association meeting in Orlando
It also cut levels of "bad" LDL cholesterol as much as 36
percent when used alone, and as much as 14 percent when taken
on top of statins, the widely used cholesterol lowering pills.
Researchers said evacetrapib showed none of the safety
signals found with a similar drug developed by Pfizer Inc . That drug, torcetrapib, also showed robust increases
in HDL, but Pfizer stopped development of the medicine in 2006
after it was found to increase deaths.
"This is highly encouraging data that you've got an agent
(evacetrapib) that has phenomenal effects on lipids and the
safety profile looks clean," said Dr. Stephen Nicholls, the
study's lead researcher and director of cardiovascular trials
at the Cleveland Clinic, who presented the data.
Statins and a raft of blood pressure medicines have
dramatically reduced the number of heart attacks and strokes
suffered by the population at large. But heart disease remains
the No. 1 killer in the world, creating an opening for more
Researchers recommended that evacetrapib begin a large,
Phase III study that will show whether the drug prevents heart
attacks and strokes, known as an outcomes trial.
David Moller, Lilly's head of endocrinology and
cardiovascular research, said the company intends to begin its
Phase III program "as soon as possible."
Two other so-called CETP drugs -- Merck & Co's
anacetrapib and Roche AG's dalcetrapib -- are already
being tested among thousands of patients to see if they show
such a benefit.
Those drugs are seen as being further along in development
than Lilly's version. A Roche spokesman said the company
expects to have final data from the first of two dalcetrapib
outcomes trials in late 2012 or early 2013
But Moller said, "At this stage, it's not clear who is
going to be first in class or who is going to be best in
All of the drugs are designed to block the cholesteryl
ester transfer protein, or CETP. Wall Street analysts have said
the CETP drugs could reap $10 billion in annual sales, but they
are skeptical that the drugs will ever reach the market, given
the fate of torcetrapib, one of the highest-profile flameouts
in the history of drug development.
The study of evacetrapib involved 398 patients with either
high levels of LDL or low levels of HDL.
In one part of the study, patients received one of three
evacetrapib doses -- 30 milligrams, 100 milligrams or 500
milligrams -- or a placebo. The HDL increase for the highest
dose was comparable to the jaw-dropping rise shown by Merck's
In another part of the study, patients received 100 mg of
evacetrapib or a placebo on top of commonly used doses of the
widely used statins Zocor, Lipitor and Crestor. For those
patients, HDL increased between 78.5 percent and 88.5 over
"You have an enormously effective drug on lipid parameters,
both HDL and LDL, whether you look at it from a monotherapy
perspective or whether you look at it in combination with the
three most commonly prescribed statins," Nicholls said.
From a safety perspective, the researchers found none of
the blood chemistry changes that doomed torcetrapib.
For example, they found no increases in blood pressure, or
adverse changes in levels of the hormone aldosterone, which
helps regulate blood pressure, or the hormone cortisol.
"We have ruled out torcetrapib-like toxicity," said Dr.
Steven Nissen of the Cleveland Clinic, the study's chairman.
While still years from potentially reaching the market,
evacetrapib could provide optimism for Lilly's research
pipeline at a time when the Indianapolis drugmaker desperately
needs it. The company's big-selling schizophrenia drug Zyprexa
began facing generic competition in the United States last
month, and two of its other biggest products lose patent
protection in 2013 and 2014.
Lilly shares were down 0.6 percent in morning trade on the
New York Stock Exchange.