LOS ANGELES — A new class of powerful cholesterol-reducing drugs is showing promising results, potentially offering a new option for people who do not respond to medication now on the market, according to studies presented at a conference of heart specialists here on Monday.
Although the final word on the effectiveness of the drugs is still a few years away, the results so far are so promising that pharmaceutical companies are racing to bring them to market.
In early- and middle-stage trials, use of the experimental drugs reduced so-called bad cholesterol by about 40 to 70 percent in a matter of weeks, equivalent to the reduction achieved by the most effective statins like Lipitor. But it appears that the new drugs can be used along with statins, lowering cholesterol even further.
“With these drugs, together with statins, you can get virtually everyone to the goal,” Dr. Frederick Raal of the University of the Witwatersrand, in Johannesburg, South Africa, who presented one of several studies on these new drugs at the American Heart Association’s scientific meeting here.
The most advanced of the drugs, which as a class are called PCSK9 inhibitors, is only now entering the final stages of clinical trials and is not likely to get to market until 2015 at the earliest.
And there are still some caveats. One is that while the drugs lower cholesterol, it has not yet been shown that they actually reduce the risk of heart attacks, strokes or other cardiovascular problems.
Furthermore, many of the studies so far have lasted no more than 12 weeks and involved fewer than 200 people. Far longer and larger studies are needed to show that the drugs would keep working over a lifetime and would be safe.
So far, however, the studies show “quite good safety,” Dr. Peter Wilson of Emory University said in a presentation here discussing the studies. “This is extremely promising.”
The drugs have to be injected, typically every two to four weeks. That means that the PCSK9 inhibitors are not likely to be widely used for “garden variety high cholesterol,” said Dr. Gordon Tomaselli, chief of cardiology at Johns Hopkins.
Still, millions of Americans cannot lower their cholesterol sufficiently using statins alone, providing a market that could reach billions of dollars in annual sales for a successful drug.
Leading the race so far is the team of Sanofi, the big French drug company, and Regeneron Pharmaceuticals, a biotechnology company in Tarrytown, N.Y.
The companies announced Monday that they were beginning a Phase 3 trial — usually the last step before filing for approval — involving 18,000 patients with a recent heart attack or worsening chest pain who cannot lower their cholesterol with statin therapy alone. The patients will inject themselves once every two weeks with either the drug or a placebo, while continuing to take statins.
The study, which will take at least two years, will determine whether the drug, known by the awkward code name SAR236553/REGN727, can reduce the rate of heart attacks, strokes and other cardiovascular problems.
In a midstage study published recently in The New England Journal of Medicine, patients who took the Sanofi drug plus a high dose of atorvastatin, the generic equivalent of Lipitor, had a mean 73 percent reduction in low-density lipoprotein cholesterol, the so-called bad cholesterol, compared with a 17 percent reduction for those taking only the high dose of the statin.
Amgen seems to be next in line, saying it plans to begin Phase 3 trials early next year. Pfizer and Roche have drugs in midstage clinical trials. Others in pursuit include Eli Lilly & Company and Alnylam.
Dr. Evan A. Stein of the Metabolic and Atherosclerosis Research Center in Cincinnati, said that about 10 to 20 percent of patients could not tolerate statins at all, or at least could not tolerate doses high enough to lower cholesterol sufficiently. Their main alternative now is Merck’s Zetia, which reduces cholesterol about 18 percent.
Dr. Stein, who is a consultant to Amgen, presented the results on Monday of a trial of Amgen’s drug, AMG 145, in such patients.
Patients receiving AMG 145 experienced an average reduction in LDL cholesterol after 12 weeks of 41 to 51 percent, depending on the dose. Those who received both AMG 145 and Zetia had an even greater average reduction — 63 percent. By contrast, those who received Zetia and a placebo had a drop in bad cholesterol of only 15 percent.
After 12 weeks, only 7 percent of the patients on Zetia alone reduced LDL to 100 milligrams per deciliter, which is the goal for many people. About 61 percent of those on the highest dose of AMG 145 did so, as did 90 percent on both AMG 145 and Zetia. The trial results were also published online by The Journal of the American Medical Association.
LDL cholesterol is removed from the blood when it binds to LDL receptors on the surface of liver cells, and then is taken inside the cells. PCSK9 — which stands for proprotein convertase subtilisin/kexin type 9 — also binds to the LDL receptor, and when it does so, the receptor is destroyed along with the LDL.
But if PCSK9 does not bind, the receptor can return to the surface of the cell and remove more cholesterol. The drugs, which in general are proteins known as monoclonal antibodies, block PCSK9 from binding to the receptor.
New Drugs for Lipids Set Off Race
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New Drugs for Lipids Set Off Race
