Niaspan(R) Combined With Low/Moderate Dosed Statin Achieves Better Total Lipid Control Vs. Higher Dose Statin Monotherapy or Zocor(R)/Zetia(R)
Kos Pharmaceuticals, Inc. (Nasdaq: KOSP):
— COMPELL study shows significantly greater reductions in
triglycerides and Lp(a), as well as superior 2.5-3.5 fold
increases in HDL-C and comparable lowering of LDL-C with
Niaspan combination therapy versus Crestor(R) and Zocor/Zetia
— Adding Niaspan to statin therapy achieves better total lipid
control for patients at high risk for heart attack
Kos Pharmaceuticals, Inc. (Nasdaq: KOSP) commented today on the results from the COMPELL (COMParative Effects on Lipid Levels of Niaspan and Statins Versus Other Lipid Therapies) Phase IV efficacy trial presented at the XIV International Symposium on Atherosclerosis. The results demonstrated that adding the HDL-boosting therapy Niaspan (niacin extended-release tablets) to statin therapy (HMG-CoA reductase inhibitors) achieved superior raising of high-density lipoprotein cholesterol (HDL-C), or “good” cholesterol, and increased triglyceride lowering, with equivalent lowering of low-density lipoprotein cholesterol (LDL-C), or “bad” cholesterol, for patients compared to treatment with a high dose statin or Zocor/Zetia (simvastatin and ezetimibe).(1)
COMPELL was a 12-week, randomized, multicenter, open-label study in 292 patients comparing the efficacy of combination therapy with Niaspan and low to moderate doses of Lipitor(R) and Crestor against moderate to high dose Crestor and Zocor/Zetia (sold as the fixed-dose combination tablet, Vytorin(R)). One-half of the patients treated were women, who required LDL-C lowering therapy according to NCEP ATP III guidelines (LDL-C more than 100 mg/dL).(2) The primary endpoint was percent change in LDL-C at week 12 from baseline compared across all treatment groups.(3) In a dose-escalation study design, Niaspan 1000 mg with Crestor 10 mg, and 20 mg, or, Niaspan 1000 mg and Lipitor 20 mg, and Niaspan 2000 mg with Lipitor 40 mg were compared with Crestor 20 mg and 40 mg or Zocor/Zetia 20mg/10mg and 40mg/10 mg.
Mean Percent Change from Baseline at Study End (Week 12) LDL-C HDL-C TG Lp(a) + ———————————————————————- Atorvastatin 40mg/Niaspan 2000mg -56% +22% -47% -20% ———————————————————————- Rosuvastatin 20mg/Niaspan 1000mg -51% +24% -40% -6% ———————————————————————- Simvastatin 40mg/Ezetimibe 10mg -58% +10%* -33%* +7%* ———————————————————————- Rosuvastatin 40mg -54% +7%* -25%* +5%* ———————————————————————-
* Significantly different (p is less than or equal to 0.05) versus atorvastatin/Niaspan
+ Lp(a) reported as median values
Study results showed that patients given Niaspan in combination with a low to moderate dose of Lipitor or Crestor achieved equivalent reduction in LDL-C (51-58%), 1.2 to 1.9-fold greater decreases in triglycerides and 2.5 to 3.5 fold greater increases in HDL-C, than patients who received high-dose Crestor or Zocor/Zetia.(4) Only patients receiving Niaspan experienced significant decreases in lipoprotein (a), referred to as Lp(a), which actually increased in patients on Crestor and Zocor/Zetia.(5) Similar numbers of patients reported adverse events and serious adverse events. No drug-related myopathy was observed.
COMPELL was presented by Peter Jones, M.D., Associate Professor of Cardiology, Baylor University. “These results are particularly powerful because they demonstrate that we can drive LDL-C levels down to goal and also raise the good cholesterol, HDL-C, without the need for high doses of statin medications,” said Dr. Jones. “The patients in the study were at high risk for heart attack. For these patients, achieving optimal goal levels for all lipid parameters, including HDL-C, LDL-C and triglycerides is essential. We found that by combining the prescription form of niacin, called Niaspan, with a low to moderate dose of a statin, we could achieve these results. When heart disease patients achieve these three goals, their risk of heart disease goes down substantially.”
“The COMPELL study puts broad dyslipidemic control and efficacy in appropriate perspective. Lowering LDL cholesterol to ultra-low levels may not be enough to protect against heart disease,” said Adrian Adams, President and CEO of Kos Pharmaceuticals. “There seems to be a diminishing rate of return in reducing coronary events when LDL is lowered progressively below 100 mg/dL. Most LDL-lowering trials show that two-thirds to three-quarters of statin-treated patients who are at risk in fact progress to a cardiovascular event, despite treatment. This research points to combining statin therapy with Niaspan, the most effective drug available for increasing HDL, as the next clinical advance in risk reduction.”
“Patients are currently being enrolled in the AIM-HIGH study, which is a landmark outcomes study sponsored in part by The National Institutes of Health to evaluate the independent effect of treating HDL-C and triglycerides with Niaspan and simvastatin versus simvastatin alone in the prevention of heart attack and stroke. This heightened awareness and recognition bodes extremely well for Kos’ highly differentiated cholesterol products, Niaspan and Advicor(R) and positions our optimized Niaspan CF and Simcor(TM) (Niaspan/simvastatin) well in what we believe is an under penetrated market with a growing emphasis on treating HDL cholesterol,” Adams continued.
The HDL-C particle facilitates “reverse cholesterol transport,” and is like a “cleaning service”, removing bad cholesterol (LDL-C) out of the arteries and back to the liver to be released into the gastrointestinal tract, where it is removed from the body.(6) The primary mechanism of statins is reducing levels of LDL-C through inhibition of cholesterol synthesis and output from the liver, but they have a much smaller effect on HDL-C levels.(7) Importantly, lowering LDL-C alone has only reduced events related to coronary artery disease by approximately 30 – 35%.(8)
Previous studies have provided evidence that supports the role of HDL-C in reducing risks associated with heart disease.
— Evidence from a smaller clinical trial known as HATS (HDL
Atherosclerosis Treatment Study) strongly suggested a
correlation between raising HDL-C levels and the slowing or
halting of atherosclerosis. HATS compared the combination of
niacin and simvastatin versus placebo and showed a 60 to 90
percent reduction in cardiac events.
— Another study, known as VA-HIT (VA High Density Lipoprotein
Intervention Trial, conducted by the Department of Veteran
Affairs), showed that raising HDL-C levels in patients with
low HDL-C with a fibrate significantly reduced coronary heart
disease events.
— The ARBITER 2 (Arterial Biology for the Investigation of the
Treatment Effects of Reducing Cholesterol) study showed that
the combination of Niaspan and a statin slowed disease
progression 68 percent more than statin monotherapy as
measured by plaque build-up in the carotid artery.
Additionally, the combination of Niaspan and statin therapy
demonstrated a 60 percent reduction of coronary events
compared with a statin used alone.
— The findings of ARBITER 3 (Atherosclerosis Regression During
Open-label Continuation of Extended-release Niacin following
ARBITER 2) showed that raising HDL-C, with a moderate dose of
Niaspan (1000 mg) removed existing plaque build-up from the
carotid arteries in patients on statin therapy with
well-controlled (less than 100 mg/dL) LDL-C. Carotid
atherosclerosis was significantly reversed in study patients
receiving Niaspan therapy for two years by an average of
-0.04mm, which is equal to a 105 percent reduction in the rate
of progression. Atherosclerosis regression was measured by the
change in carotid intima-media thickness (CIMT), a recognized
surrogate outcome marker in which a sub-millimeter increase in
arterial wall thickness (plaque build-up) predicts an increase
in heart disease risk. ARBITER 3 showed definite
atherosclerosis regression 12-24 months following treatment
with Niaspan, thereby confirming that sustained increases in
HDL-C are independently associated with superior effects on
atherosclerosis regression. These results reinforce the
benefit of raising HDL-C in patients with well-controlled
LDL-C levels.
About Niaspan
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 or coronary artery disease and hypercholesterolemia. Niacin, in combination with a bile acid binding resin, is indicated to slow progression or promote regression of atherosclerotic disease.
Niaspan is contraindicated in patients with allergies to any of its ingredients, active peptic ulcer disease, significant or unexplained persistent liver dysfunction, or arterial bleeding. Niaspan should not be substituted for equivalent doses of immediate-release niacin. Niaspan should be prescribed with caution in patients who consume substantial amounts of alcohol and/or have a past history of liver disease. Liver function tests should be performed on all patients during therapy with Niaspan. Use of Niaspan with other lipid-altering medications called statins may increase the risk of rhabdomyolysis, a rare condition that causes muscles to breakdown. The most common side effect with Niaspan is flushing of the skin. Other commonly reported side effects include indigestion, headache, pain, abdominal pain, nausea, itching, diarrhea, running nose, vomiting and rash. Patients with diabetes should carefully monitor their blood sugar and report changes to their doctor.(9)
About Kos Pharmaceuticals, Inc.
Kos Pharmaceuticals, Inc. is a fully integrated specialty pharmaceutical company engaged in developing, commercializing, manufacturing and marketing proprietary prescription products for the treatment of chronic diseases with a particular focus on the cardiovascular, metabolic and respiratory disease areas. The Company’s principal product development strategy is to reformulate existing pharmaceutical products with large market potential to improve safety, efficacy, and patient compliance. Kos’ strategy also includes making measured investments in new chemical entity research through in-house and sponsored research, scientific in-licensing and general corporate development activities. The Company currently markets Niaspan and Advicor for the treatment of cholesterol disorders, Azmacort(R) for the treatment of asthma, Cardizem(R)LA for the treatment of hypertension and angina, and Teveten(R) and TevetenHCT for the treatment of hypertension. Kos has a strong and growing research and development pipeline including proprietary drug delivery technologies in solid-dose, inhalation and aerosol metered-dose device administration to help fuel sustained, organic sales growth into the future.
Certain statements in this press release, including statements relating to Niaspan, the results of the COMPELL study and other studies, including but not limited to the HATS, VA-HIT, ARBITER 2 and ARBITER 3 studies, the growing emphasis on the treatment of HDL cholesterol, the potential increase in market growth for cholesterol combination therapies, the growth prospects of the markets in which the Company’s products compete, the Company’s strong and growing research and development pipeline and future sales growth are forward-looking and are subject to risks and uncertainties which may cause actual results to differ materially from those projected in a forward-looking statement. These risks and uncertainties include the protection afforded by the Company’s patents and those related to its acquired and licensed products, the ability to build awareness for the Company’s products within the medical community, the continuing growth of the cardiovascular, respiratory and allergy markets, the Company’s ability to increase the size of its sales force and to attract and retain sales professionals, the Company’s and its licensors’ ability to achieve regulatory approvals for products under development and to successfully launch such products in a timely manner, including optimized Niaspan CF and Simcor, the ability of third party suppliers to the Company continuing to be able to perform their supply obligations, the Company’s ability to entered into additional new business development opportunities, the progress of the Company’s research and development pipeline, the effect of conditions in the pharmaceutical industry and the economy in general, as well as certain other risks. A more detailed discussion of risks attendant to the forward-looking statements included in this press release are set forth in the “Forward-Looking Information: Certain Cautionary Statements” section of the Company’s Annual Report on Form 10-K for the year ended December 31, 2005, filed with the Securities and Exchange Commission, and in other reports filed with the SEC. All information in this press release is as of June 20, 2006 and the Company undertakes no duty to update this information.
(1)McKenney JM, Jones PH, Bays HE, Knopp RH, Kashyap ML, Ruoff GE, Stanek EJ, McGovern ME. Comparative Lipid Effects of Combination Therapy with a Statin and Extended-Release Niacin Versus Statin Plus Ezetimibe Versus a Statin Alone. (Abstract presented at the XIV International Symposium on Atherosclerosis.)
(2)McKenney JM, Jones PH, Bays HE, Knopp RH, Kashyap ML, Ruoff GE, Stanek EJ, McGovern ME. Comparative Lipid Effects of Combination Therapy with a Statin and Extended-Release Niacin Versus Statin Plus Ezetimibe Versus a Statin Alone. (Abstract presented at the XIV International Symposium on Atherosclerosis.)
(3)McKenney JM, Jones PH, Bays HE, Knopp RH, Kashyap ML, Ruoff GE, Stanek EJ, McGovern ME. Comparative Lipid Effects of Combination Therapy with a Statin and Extended-Release Niacin Versus Statin Plus Ezetimibe Versus a Statin Alone. (Abstract presented at the XIV International Symposium on Atherosclerosis.)
(4)McKenney JM, Jones PH, Bays HE, Knopp RH, Kashyap ML, Ruoff GE, Stanek EJ, McGovern ME. Comparative Lipid Effects of Combination Therapy with a Statin and Extended-Release Niacin Versus Statin Plus Ezetimibe Versus a Statin Alone. (Abstract presented at the XIV International Symposium on Atherosclerosis.)
(5)McKenney JM, Jones PH, Bays HE, Knopp RH, Kashyap ML, Ruoff GE, Stanek EJ, McGovern ME. Comparative Lipid Effects of Combination Therapy with a Statin and Extended-Release Niacin Versus Statin Plus Ezetimibe Versus a Statin Alone. (Abstract presented at the XIV International Symposium on Atherosclerosis.)
(6)The Difference Between LDL and HDL Cholesterol. American Heart Association. 2005. Available at www.americanheart.org; accessed data 6/6/06
(7)Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497.
(8)Bays, H. Existing and investigational combination drug therapy for high-density lipoprotein cholesterol. Am J Cardiol 2002;90(suppl):30K-43K.
(9)NIASPAN (prescribing information). Cranbury, NJ: Kos Pharmaceuticals, Inc. 2005