Reports on New Patented Drugs – Crestor

Brand Name: Crestor

Generic Name: rosuvastatin calcium

DIN: 02247162 10 mg tablet
02247163 20 mg tablet
02247164 40 mg tablet

Patentee: AstraZeneca Canada Inc.

Indication – as per As an adjunct to diet, at least equivalent to the Adult Treatment product monograph: Panel III (ATP III TLC diet), for the reduction of elevated total cholesterol, LDL-cholesterol, ApoB, the total cholesterol; HDL-cholesterol ratio and triglycerides and for increasing HDL-C; in hyperlipidemic and dyslipidemic conditions, when response to diet and exercise alone has been inadequate including: primary hypercholesterolemia, combined dyslipidemia, and homozygous familial hypercholesterolemia.

Notice of Compliance: February 18, 2003

Date of First Sale: February 19, 2003

ATC Class: C10AA07
Serum lipid reducing agents Cholesterol and triglyceride reducers HMG CoA reductase inhibitors

Application of the Guidelines

Summary:

The introductory prices of Crestor were found to be within the Guidelines because the cost of therapy did not exceed the cost of therapy of existing drugs in the therapeutic class comparison and the prices did not exceed the range of prices in other comparator countries where Crestor was sold.

Scientific Review:

Crestor is a new active substance and the PMPRB´s Human Drug Advisory Panel (HDAP) recommended that Crestor be reviewed as a category 3 new medicine (provides moderate, little or no therapeutic advantage over comparable medicines).

The Therapeutic Class Comparison (TCC) test of the Guidelines provides that the price of a category 3 new drug product cannot exceed the prices of other drugs that treat the same disease or condition. Comparators are generally selected from among existing drug products in the same 4th level of the Anatomical, Therapeutic, Chemical (ATC) System that are clinically equivalent in addressing the approved indication. See the PMPRB´s Compendium of Guidelines, Policies and Procedures for a more complete description of the Guidelines and the policies on TCCs.

Other agents in the same 4th level ATC class, HMG-CoA reductase inhibitors (commonly known as ‘statins´), available on the Canadian market, include Zocor (simvastatin), Mevacor (lovastatin), Pravachol (pravastatin), Lescol (fluvastatin), and Lipitor (atorvastatin). These statins share similar indications, have been compared directly to Crestor in clinical trials, and are referred to interchangeably in the U.S. and Canadian dyslipidemia guidelines.

In its review of Crestor, the HDAP noted that the lipid lowering effects of statins have increased, with Crestor having the greatest impact on lipid levels. The recommended comparable dosage regimens for Crestor were based on the comparative clinical trial data identified (see Evidence/References).

For purposes of the Guidelines, the HDAP attempted to identify comparable dosages of the other statins, but this was not always possible because of the greater efficacy of Crestor in lowering lipid levels. The table below shows the range of costs of treatment with the statins included in the TCC based on the range of approved dosages.

Price Review:

Under the Guidelines, the introductory price of a new category 3 drug product will be presumed to be excessive if it exceeds the price of all of the comparable drug products in the TCC test, or if it exceeds the prices of the same medicine in the seven countries listed in the Patented Medicines Regulations. The price of Crestor was within the Guidelines as the daily cost of therapy did not exceed the cost of therapy with the comparator medicines.

1. Liste de médicaments du Québec, October 2003
2. There are four manufacturers of this generic medication.
3. There are seven manufacturers of this generic medication.

In 2003, Crestor 10 mg, 20 mg and 40 mg tablets were also being sold in the United Kingdom and the United States. In compliance with the Guidelines, the price in Canada did not exceed the range of prices in those countries; the prices of Crestor 20 mg and 40 mg were lower than the prices in those countries and the price of Crestor 10 mg was second lowest, below the median of international prices.

References – Crestor

Product monograph of Crestor (rosuvastatin). Astra Zeneca, Mississauga, ON. February 2003.

Carswell CI, Plosker GL, Jarvis B. Rosuvastatin. Drugs 2002; 62:2075-85. (electronic)

Chong PH, Yim BT. Rosuvastatin for the treatment of patients with hypercholesterolemia. Ann Pharmacother 2002;36(1):93-101. (electronic)

Olsson AG, Pears J, McKellar J, Mizan J, Raza A. Effect of rosuvastatin on low-density lipoprotein cholesterol in patients with hypercholesterolemia. Am J Cardiol 2001;88:504-8. (electronic)

Davidson M, Ma P, Stein EA et al. Comparison of effects of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with rosuvastatin versus atorvastatin in patients with type IIa or Iib hypercholesterolemia. Am J Cardiol 2002;89:268-75. (electronic)

Paoletti R, Fahmy M, Mahla G, Mizan J, Southworth H. Rosuvastatin demonstrates greater reduction of low-density lipoprotein cholesterol compared with pravastatin and simvastatin in hypercholesterolemia patients: a randomized, double-blind study. J Cardiovascular Risk 2001;8:383-90. (hard copy)

Brown WV, Bays HE, Hassman DR et al. Efficacy and safety of rosuvastatin compared with pravastatin and simvastatin in patients with hypercholesterolemia: a randomized, double-blind, 52 week trial. Am Heart J 2002; 144:1036-43. (hard copy)

Olsson AG, Istad H, Luurila O et al. Effects of rosuvastatin and atorvastatin compared over 52 weeks of treatment in patients with hypercholesterolemia. Am Heart J 2002; 144:1044-51. (hard copy)

Schneck DW, Knopp RH, Ballantyne CM, McPherson R, Chitra RR, Simonson SG. Comparative effects of rosuvastatin and atorvastatin across their dose ranges in patients with hypercholesterolemia and without active arterial disease. Am J Cardiol 2003;91:33-41. (hard copy)

Hunninghake DB, Chitra RR, Simonson G et al. Treatment of hypertriglyceridemic patients with rosuvastatin. Diabetes 2001;50(suppl 2):A143. (hard copy)

Stein E, Strutt KL, Miller E. ZD4522 is superior to atorvastatin in the treatment of patients with heterozygous familial hypercholesterolemia. J Am Coll Cardiol 2001;37 (suppl A):292. (hard copy)

Anon. Managing dyslipidemia: Update on guidelines and pharmacotherapy. J Am Pharm Assoc 2002;42(5)suppl 5:S36-7. (hard copy)

Chong PH. Lack of therapeutic interchangeability of HMG-CoA reductase inhibitors. Ann Pharmacother 2002;36(12):1907-17. (electronic)

Fodor JG, Frohlich JJ, Genest JJG, McPherson PR. Recommendations for the management and treatment of dyslipidemia. CMAJ 2000;162(10):1441-7. (electronic)

Anon. Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). National Institute of Health, May 2001, NIH Publication Number 01-3670. (electronic)

Stein EA. Introduction: Rosuvastatin – an efficacy assessment based on pooled trial data. Am J Cardiol 2003;91(5A):1-2C. (electronic)

Blasseto JW, Stein EA, Brown WV et al. Efficacy of rosuvastatin compared with other statins at selected starting doses in hypercholesterolemic patients and in special population groups. Am J Cardiol 2003;91(5A):3-10C. (electronic)

Shepherd J, Hunninghake DB, Barter P et al. Guidelines for lowering lipids to reduce coronary artery disease risk: A comparison of rosuvastatin with atorvastatin, pravastatin, and simvastatin for achieving lipid-lowering goals. Am J Cardiol 2003;91(5A):11-19C. (electronic)

Rader DJ, Davidson MH, Caplan RJ, Pears JS. Lipid and Apolipoprotein ratios: association with coronary artery disease and effects of rosuvastatin compared with atorvastatin, pravastatin, and simvastatin. Am J Cardiol 2003;91(5A):20-4C. (electronic)

Ballantyne CM, Stein EA, Paoletti R et al. Efficacy of rosuvastatin 10 mg in patients with the metabolic syndrome. Am J Cardiol 2003;91(5A):25-8C.

Repchinsky C, editor. Compendium of Pharmaceutical and Specialties, 38th ed. Canadian Pharmacists Association. 2003, Ottawa.