Report on New Patented Drugs – Spiriva

Brand Name: Spiriva

Generic Name: tiotropium bromide

DIN: 02246793
18 mcg per capsule

Patentee: Boehringer Ingelheim Canada Ltd

Indication (as per product monograph): Spiriva (tiotropium bromide) is indicated for the long term, once daily, first line maintenance treatment of bronchospasm and relief of dyspnea associated with chronic obstructive pulmonary diseases (COPD), including chronic bronchitis and emphysema.

Notice of Compliance: November 20, 2002

Date of First Sale: November 21, 2002

ATC Class: RO3BB04
Drug for obstructive airway diseases; other drugs for obstructive airway diseases, inhalants; anticholinergics

Application of the Guidelines

Summary:

The introductory price of Spiriva was 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 price did not exceed the range of prices in other comparator countries where Spiriva was sold.

Scientific Review:

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

Spiriva is the second entry in its 4th level ATC class to be introduced in Canada. The only other medication within the same 4th level ATC class is Atrovent (ipratropium). Atrovent is the only other anticholinergic presently on the Canadian market for the treatment of COPD, emphysema and chronic bronchitis. The results of two comparative clinical trials (van Noord et al and Vicken et al) suggest that Spiriva is more efficacious than Atrovent.

The most recently published guidelines on the management of COPD (Chronic Obstructive Lung Disease Workshop Summary 2001) state that bronchodilators are central to symptom management of COPD. Bronchodilators listed in the guidelines include the anticholinergic ipratropium, the long-acting beta agonists formoterol and salmeterol, short acting beta agonists salbutamol, terbutaline, and fenoterol, and the methylxanthines aminophylline and theophylline.

The inhaled bronchodilators are preferred over the oral methylxanthines as the methylxanthines may cause more adverse effects, require regular blood work and can interact with several other medications. Methylxanthines are not first line and they are not available in inhalation form. The HDAP did not recommend their inclusion in the TCC for Spiriva.

The HDAP recommended all single agent inhaled bronchodilators used in the management of COPD be included in the TCC for Spiriva. These are Serevent (salmeterol), Foradil (formotorol), Oxeze (formotorol), Atrovent (ipratropium), Ventolin (salbutamol), Berotec (fenotorol), and Bricanyl (terbutaline).

The PMPRB's Guidelines provide that the dosage recommended for comparison purposes will normally not be higher than the maximum of the usual recommended dosage. The recommended comparable dosage regimens for Spiriva and the comparators are based on their respective product monographs and supported by clinical literature. See the table below.

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. The Guidelines provide that it may, however, be appropriate to include products from other ATC classes if they are clinically equivalent for the appropriate indication to the drug product under review. See the PMPRB's Compendium of Guidelines, Policies and Procedures for a more complete description of the Guidelines and the policies on TCCs.

Price Review:

Under the Guidelines, the introductory price for a new category 3 drug product will be presumed to be excessive if it exceeds the price of all of the comparable drug products based on the TCC test, or if it exceeds the prices of the same medicine in the seven countries listed in the Patented Medicines Regulations.

As shown in the following table, the price of Spiriva was within the Guidelines relative to the TCC test as it did not exceed the prices of the other drugs in the therapeutic class.

1 Provincial Reimbursement Advisor, May 2003
2 Ontario Drug Benefit Formulary, 2002

In 2002, Spiriva was also sold in Germany, Sweden, and the United Kingdom. In compliance with the Guidelines, the price in Canada did not exceed the range of prices in those countries. The price in Canada was the lowest of these countries.

Where comparators and dosage regimens are referred to in the Summary Reports, they have been selected by the PMPRB Staff and the HDAP for the purpose of carrying out the PMPRB's regulatory mandate, which is to review the prices of patented medicines sold in Canada to ensure that such prices are not excessive. The publication of these reports is also part of the PMPRB's commitment to make its price review process more transparent.

The information contained in the PMPRB's Summary Reports should not be relied upon for any purpose other than its stated purpose and is not to be interpreted as an endorsement, recommendation or approval of any drug nor is it intended to be relied upon as a substitute for seeking appropriate advice from a qualified health care practitioner.

References – Spiriva

1. Spiriva product monograph, November 6, 2002.

2. Hvizdos KM, Goa KL. Tiotropium bromide. Drugs 2002;62(8):1195-1203.

3. van Noord JA, Bantje TA, Eland ME et al. A randomized controlled comparison of tiotropium and ipratropium in the treatment of chronic obstructive pulmonary disease. Thorax 2000;55(4):289-94.

4. Vincken W, van Noord JA, Greefhorst APM et al. Improved health outcomes in patients with COPD during 1 yr=s treatment with tiotropium. Eur Resp J 2002;19(2):209-16.

5. Donohue JF, van Noord JA, Bateman ED et al. A 6-month, placebo-controlled study comparing lung function and health status changes in COPD patients treated with tiotropium or salmeterol. Chest 2002;122(1):47-55.

6. Pauwels RA, Buist AS, Calverley PMA et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: NHLBI/WHO global initiative for chronic obstructive lung disease (GOLD) workshop summary. Am J Respir Crit Care Med 2001;163:1256-76.

7. Gray J (ed). Therapeutic Choices, 3rd edition. Canadian Pharmacists Association, 2000; Ottawa.

8. Welbanks L, editor. Compendium of Pharmaceuticals and Specialties, 37th Edition. Canadian Pharmacists Association, 2002, Ottawa.

9. CCOHTA. Tiotropium: A potential replacement for ipratropium in patients with COPD. Issues in Emerging Health Technologies 2002;35:1-4.

10. Skukla VK, et al. Long-acting B2-agonists for maintenance therapy of stable chronic pulmonary obstructive disease: a systematic review. CCOHTA Technology Report 2002;27:1-40.