>>Merck Experimental Drug Boosts Good Cholesterol In Study
Last update: 10/4/2007 4:30:00 PM
By Peter Loftus
Of DOW JONES NEWSWIRES
An experimental Merck & Co. (MRK) drug more than doubled levels of "good" cholesterol in a new study, and didn't raise blood pressure like a similar Pfizer Inc. (PFE) compound did.
But Merck, of Whitehouse Station, N.J., still hasn't decided whether to continue development of its drug, anacetrapib, formerly known as MK-0859. It's waiting to see more data that may shed light on why the Pfizer compound failed in tests last year, a Merck executive said Wednesday.
A drug that substantially boosts good cholesterol, or HDL, could be a big seller if it reaches market. Doctors believe raising HDL could help further reduce the risk of heart attacks and related disease beyond what has been accomplished by drugs known as statins, which primarily lower bad cholesterol levels, or LDL. Pfizer's Lipitor statin reigns as the best-selling drug in the world with nearly $13 billion in annual sales.
Merck, Pfizer of New York and Switzerland's Roche Holding AG (RHHBY) are in various stages of developing drugs known as inhibitors of cholesteryl ester transfer protein, or CETP, which can raise good cholesterol levels.
The effort, however, suffered a big blow last year when Pfizer abandoned development of its most advanced CETP compound, torcetrapib. A large study was halted after it showed an increased death rate among those taking the drug.
Torcetrapib's failure raised concerns that the entire CETP-inhibitor category was flawed. But it's possible that torcetrapib had a unique flaw - one problem was its tendency to boost blood pressure. Other CETP compounds, however, including two in Pfizer's earlier-stage pipeline, haven't yet been linked to higher blood pressure in studies.
Late last year, Merck confirmed that it was developing a CETP inhibitor, and said a mid-stage, or Phase 2, study showed that it boosted good cholesterol without boosting blood pressure. Merck was scheduled to present the details of that study Thursday at a medical conference in New York; the results haven't yet been published in a peer-reviewed medical journal.
In the study, 589 patients with abnormal cholesterol levels received various dose levels of anacetrapib, alone or in combination with Lipitor, or a dummy pill, for eight weeks. Those on anacetrapib alone had increases in good cholesterol, or HDL, ranging from 44% to 139%, from an increase of 4% for those on placebo.
The increase in HDL levels produced by higher doses of the Merck compound appears to be well above that achieved by other drugs. In comparison, Abbott Laboratories' (ABT) Niaspan boosted HDL by up to about 26% in clinical studies, according to its product label.
In the latest study, anacetrapib users also experienced decreases in bad cholesterol ranging from 16% to 39%, from a 2% increase in the placebo group.
Patients who took both anacetrapib and Lipitor had similar increases in good cholesterol to the monotherapy group, but additional decreases in bad cholesterol, or LDL. Merck envisions anacetrapib being taken along with a statin if it reaches market. Merck plans to sell anacetrapib as a standalone product, but it hasn't rule out also combining it with a statin in a single pill.
Most important, the Merck compound wasn't associated with an increase in blood pressure in any treatment arm, according to Dan Bloomfield, a senior director with Merck's research arm.
Still, further study is needed before Merck can submit anacetrapib for regulatory approval, which could take a few years. An additional, Phase 3, study would probably have to measure the compound's effect on heart attacks and other cardiovascular events, in addition to tracking changes in cholesterol.
"The ultimate benefits of CETP inhibition on clinical outcomes have not yet been established," Bloomfield said in an interview Wednesday. "Having a compound like ours, that doesn't raise blood pressure, may give us an opportunity to test the mechanism of a compound that doesn't have off-target toxicity."
Before Merck decides whether to proceed with testing, it will evaluate data on Pfizer's torcetrapib that is expected to be presented at the annual meeting of the American Heart Association in early November, he said. The data might shed light on whether torcetrapib had a unique flaw that caused problems, or if the culprit was the CETP-inhibition mechanism.
The rate of side effects in the Merck study was similar in all treatment groups. Common ones included headache and nausea.
A Roche executive said earlier this week the company will decide soon on the future development of its experimental CETP inhibitor, R1658, which is also in Phase 2 testing. Pfizer said in the summer it hasn't advanced testing of two other CETP inhibitors beyond Phase 1.
Merck is working on another drug to boost good cholesterol that uses a different mechanism than CETP inhibition. The company has applied for Food and Drug Administration approval of Cordaptive, which contains a similar ingredient to Abbott's Niaspan, but is designed to minimize a common skin side effect of Niaspan known as flushing.
-By Peter Loftus, Dow Jones Newswires; 215-656-8289; peter.loftus@dowjones.com<<
Cheers, Tuck |
