Abbott announced that the new data released recently showed that its Simcor, an investigational, fixed-dose combination of Abbott's proprietary extended-release niacin, Niaspan, and simvastatin met its primary endpoint of lowering plaque-promoting non-HDL cholesterol (total cholesterol minus HDL), while demonstrating improvements on other key lipids, LDL "bad" cholesterol, HDL "good" cholesterol and triglycerides.
Results from this phase III clinical trial, Seacoast, were presented as part of the American Heart Association's Scientific Sessions.
Patients in the study treated with a Simcor combination containing 20 mg simvastatin had significantly better reductions in non-HDL cholesterol compared to 20 mg simvastatin therapy alone, as well as significant improvements in HDL and triglyceride levels. Patients receiving a Simcor combination with 40 mg simvastatin experienced reductions in non-HDL comparable to 80 mg simvastatin alone, and significantly better improvements in HDL and triglycerides compared with 80 mg simvastatin alone. Flushing is the most commonly reported side effect associated with Niaspan. It is generally mild and can be lessened by taking aspirin 30 minutes prior to taking the medication at bedtime. Six per cent of patients on the combination discontinued therapy due to flushing compared to 0.8 per cent with simvastatin alone.
Simcor combines two well-established and leading medications, Niaspan and simvastatin, to target multiple lipid parameters - LDL, HDL and triglycerides - in a single pill. Abbott submitted its New Drug Application to the Food and Drug Administration for Simcor in April 2007. The submission includes data from the phase III pivotal Seacoast trial.
"Patients know that it's important to manage the "bad" cholesterol, but it's essential to control HDL and triglyceride levels as well. With the SEACOAST study, SIMCOR provided comparable LDL lowering to simvastatin with significant benefit in raising good cholesterol and lowering triglycerides. This type of combination approach could be an important tool in treating patients with complex lipid disorders," said Christie Ballantyne, M.D., Baylor College of Medicine and Methodist DeBakey Heart Cent er, Houston, Texas, and lead investigator on the study. "
The 24-week double blind, randomised, controlled trial in more than 600 patients with elevated non-HDL (type II hyperlipidemia or mixed dyslipidemia) compared simvastatin alone to a combination of Abbott's extended-release niacin combined with simvastatin. The study was designed to evaluate the safety and efficacy of the SIMCOR combination following simvastatin monotherapy. Patients enrolled in the trial were assigned to either a low-dose (20 mg) or high-dose (40 mg) simvastatin group. Patients in the low-dose group were randomised to receive Niaspan 2000 mg/simvastatin 20 mg, Niaspan 1000 mg/simvastatin 20 mg, or simvastatin 20 mg. Patients in the high-dose group were randomised to receive Niaspan 2000 mg/simvastatin 40 mg, Niaspan 1000 mg/simvastatin 40 mg or simvastatin 80 mg. Those in the simvastatin control groups received a 50 mg dose of immediate-release niacin to maintain blinding.
Patients in the low-dose group receiving combination treatment achieved 14 per cent (1000 mg/20 mg) and 23 per cent (2000 mg/20 mg) reductions in non HDL compared to a 7 per cent reduction with 20 mg simvastatin therapy alone. Additionally, combination treatment resulted in significant improvements in HDL of 18 per cent (1000 mg/20 mg) and 25 per cent (2000 mg/20 mg) compared to 7 per cent with 20 mg simvastatin alone. Similarly, significant reductions in triglycerides of 27 per cent (1000 mg/20 mg) and 38 per cent (2000 mg/20 mg) were seen in those treated with combination therapy compared to a 15 per cent reduction with simvastatin monotherapy.
In the high-dose group, patients treated with SIMCOR combination therapy showed similar (non-inferior) improvements in non-HDL of 11 per cent (1000 mg/40 mg) and 17 per cent (2000 mg/40 mg) compared to a 10 per cent improvement with 80 mg simvastatin therapy alone. Additionally, the high-dose combination group demonstrated significant improvements in HDL of 15 per cent (1000 mg/40 mg) and 22 per cent (2000 mg/40 mg) compared to a 1 per cent decrease among those receiving 80 mg simvastatin monotherapy. Triglyceride levels among the high-dose combinations groups dropped 23 per cent and 32 per cent, respectively, in contrast to a 0.3 per cent increase in those randomised to 80 mg simvastatin monotherapy.
Treatment with the four different doses of Niaspan combined with simvastatin for 24 weeks was well tolerated. There was no evidence for increased risk of hepatotoxicity or myopathy with the combination.
Treatment of high cholesterol has long centred on the use of statins, including simvastatin, to lower LDL cholesterol, which has been the primary target of therapy. Clinical consensus now also emphasizes the importance of comprehensive cholesterol management, including management of HDL levels, in impacting cardiovascular risk.
In fact, a recent post-hoc analysis of 9,770 patients from the Treating to New Targets study, published in the New England Journal of Medicine, concluded HDL levels were predictive of major cardiovascular events in patients treated with statins, and also observed in patients with LDL levels below the National Cholesterol Education Programme's most aggressive target of 70 mg/dL.
"We hope to make comprehensive cholesterol treatment more effective, more tolerable and more convenient for patients at risk for cardiovascular disease," said Eugene Sun, M.D., vice president, Global Clinical Development, Abbott.
Available since 1997, Niaspan is the only FDA-approved, once-daily extended-release prescription formulation of niacin for treating abnormal cholesterol levels.
Niaspan is indicated as an adjunct to diet when the response to a diet restricted in saturated fat and cholesterol and other nonpharmacologic measures alone has been inadequate, to reduce elevated total cholesterol, LDL-C, Apo B, and triglyceride levels, and to increase HDL-C in patients with primary hypercholesterolemia and mixed dyslipidemia. In patients with a history of myocardial infarction and hypercholesterolemia, niacin is indicated to reduce the risk of recurrent non-fatal myocardial infarction. In patients with coronary artery disease and hypercholesterolemia, niacin, in combination with a bile acid binding resin, is indicated to slow progression or promotes regression of atherosclerotic disease.
Abbott is a global, broad-based health care company devoted to the discovery, development, manufacture and marketing of pharmaceuticals and medical products, including nutritionals, devices and diagnostics. The company employs 65,000 people and markets its products in more than 130 countries.