UPDATE 2-Lilly drug boosts good cholesterol, appears safe

Tue Nov 15, 2011 11:50am EST

* 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 (Reuters) - 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 on Tuesday.

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 effective medicines.

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 class."

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 anacetrapib.

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 statins alone.

"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.