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Kos' Advicor poised for marketing
With increasing identification of various atherogenic lipids and a persistent calling for lower target lipid levels, controlling dyslipidemia with monotherapy is becoming less and less realistic. As a result, some pharmaceutical manufacturers are directing a significant portion of their R&D efforts to combination products such as lovastatin and niacin (Advicor, formerly called Nicostatin, Kos Pharmaceuticals).
New studies of combination therapy with low doses of two standard lipid-modulating drugs confirm earlier studies showing that a combo compound is more efficacious than high doses of either drug alone to treat dyslipidemia. Advicor is a once-daily single-tablet formulation of lovastatin and sustained-release niacin. Kos received an approvable letter from the Food & Drug Administration for the product and expects formal approval in December when the patent for lovastatin (Mevacor, Merck) expires. Advicor is aimed at such common disorders as primary hypercholesterolemia and hyperlipidemia.
As Daniel M. Bell, chairman and CEO of Kos, put it during an International Symposium on Drugs Affecting Lipid Metabolism held in New York City, "Kos looks forward to launching Advicor into the fast-growing $10 billion U.S. cholesterol-altering market early in 2002."
"Nothing is better than a statin for lowering LDL levels," said Judy W. M. Cheng, Pharm.D., clinical pharmacy specialist in cardiology, Mount Sinai Medical Center, New York City, in an interview. "Aggressive cholesterol lowering with statins can prevent unstable angina and myocardial infarction ... and reduce the need for surgical revascularization."
Since all the statins seem to have a similar mechanism of action and side-effect profile, she added, "we are still puzzled by what happened to cerivastatin," (Baycol, Bayer), which was removed from the market due to reported deaths. "But we haven't heard of a problem with lovastatin." While it would be wise to monitor patients more carefully when using these drugs, she continued, "the plight of Baycol would not inhibit us from recommending other statins." Side effects with statins alone are uncommon.
Niacin has always been useful in reducing high LDL levels, but because of its side effects, it is problematic when used in high doses. And it requires physician supervision, Cheng noted. But low-dose niacin plus a statin used singly have helped patients, not only by cutting LDL but also normalizing triglycerides and raising HDL. "One dose of the new combination should maintain a steady level throughout the day, with no peaks and troughs," she said.
The main advantage of Advicor, in Cheng's view, is convenience rather than efficacy. "Of course, people would prefer one pill to two." But, she emphasized, "in this case, price is key." If Advicor is too expensive, "doctors will tell their patients to simply continue to take the two separate drugs, instead of the pricey compound," she told Drug Topics, adding, "At Mount Sinai, we'll wait to learn the price before we decide whether to include Advicor on the formulary."
In one of the new studies of the combo drug presented at the symposium, Donald B. Hunninghake, M.D., professor of medicine and pharmacology at the University of Minnesota, and co-workers looked at the dose-ranging, dose-sparing effects of Advicor in 237 hyperlipidemic patients over 28 weeks. Patients were randomized either to two Advicor groups or to one group receiving lovastatin alone or another receiving extended-release niacin alone. The dosage was raised gradually in some patients during the entire period, in others it remained the same after 12 weeks.
Compared with its component parts analyzed separately, Advicor had "pronounced, positive dose-related effects on all major lipids," the researchers concluded. "It had dose-sparing effects on LDL-C, HDL-C, and triglycerides." Dose-sparing means there is a reduction of "bad" cholesterol and an increase of "good" cholesterol with a lower dose of Advicor than with higher doses of lovastatin or niacin separately. "The broad-spectrum effects [of Advicor] on the plasma lipids in this study should translate into significant clinical benefits," Hunninghake concluded.
Naomi PFEIFFER. Lipid modifier combining statin and niacin to bow in 2002.