Report on New Patented Drugs - Alphagan

Under its transparency initiative, the PMPRB publishes the results of the reviews of new patented drugs by Board Staff, for purposes of applying the PMPRB's Price Guidelines, for all new active substances introduced after January 1, 2002.

Alphagan

Brand Name: Alphagan

Generic Name: brimonidine tartrate

DIN: 2236876 2 mg/mL (0.2%)

Patentee: Allergan Inc.

Indication (as per product monograph):

For the control of intraocular pressure (IOP) in patients with chronic open angle glaucoma (OAG) or ocular hypertension (OH).

Alphagan 0.5% is indicated for the prevention of post-operative IOP spikes and for lowering IOP from pre-operative levels in patients undergoing argon laser trabeculoplasty (ALT).

Notice of Compliance: November 24, 1997

Date of First Sale: December 17, 1997

Date of First Patented Sale: September 3, 2002

In most case, patents are issued before the drug comes to market. In this case, the first patent pertaining to Alphagan was issued September 3, 2002 and it came under the PMPRB's jurisdiction at that time.

ATC Class: S01EA05

Ophthalmologicals, Antiglaucoma Preparations and Miotics, Sympathomimetics in Glaucoma therapy.

Application of the Guidelines

Summary:

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

Scientific Review:

Alphagan is a new active substance and the Human Drug Advisory Panel (HDAP) reviewed it 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. 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.

The HDAP identified only one agent in the same 4th level ATC that is indicated and used for the control of intraocular pressure in patients with chronic open angle glaucoma or ocular hypertension, Propine (dipivefrin). Based on comparative clinical trials, the HDAP also identified Trusopt (dorzolamide), Xalatan (latanoprost), Isopto Carpine and Timoptic (timolol) as comparators as these drug products are used in the control of intraocular pressure in patients with chronic open angle glaucoma or ocular hypertension.

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 Alphagan and the comparators are based on respective product monographs and comparative clinical trial data.

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 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 Alphagan was within the Guidelines as the daily cost of therapy did not exceed the cost of therapy with the comparator medicines.

Name Dosage Regimen/Day Cost per Day1
Alphagan (brimonidine tartrate) 4 drops (0.2 mL) $0.6600
Propine (dipivefrin) 4 drops (0.2 mL) $0.3162
Trusopt (dorzolamide) 6 drops (0.3 mL) $0.9900
Xalatan (latanoprost) 2 drops (0.1 mL) $1.0400
Isopto Carpine (pilocarpine) 8 drops (0.4 mL) $0.1226
Timoptic (timolol) 4 drops (0.2 mL) $0.5112

1 Ontario Drug Benefit Formulary, January 2003

At the time of introduction, Alphagan was also being sold in France, Germany, the United Kingdom and the United States. In compliance with the Guidelines, the price in Canada did not exceed the range of prices in these countries; the price of Alphagan was the lowest of these countries. In 2003, Alphagan was sold in all seven comparator countries (France, Germany, Italy, Sweden, Switzerland, U.K. and U.S.) and the price in Canada was 4th highest 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.

Evidence/Reference:

American Academy of Ophthalmology Preferred Practice Patterns Committee Glaucoma Panel. Primary Open-Angle Glaucoma. American Academy of Ophthalmology. 2000.

Brief prescribing information of Pilopine HS. Electronic copy available http://www.alconlabs.com/ca_en/aj/products/anti-glau1.jhtml (Accessed March 13, 2003).

Boucher M. Glaucoma: Keep a close eye on your patients. Pharm Pract 2000;16(2):61-4, 66.

Centofanti M, Manni G, Gregori D, et al. Comparative effects of brimonidine 0.2% versus dorzolamide 2% combined with beta-blockers in glaucoma. Graaefe's Arch Clin Exp Ophthalmol 2000;238:302-5.

Drug Product Database on the Health Canada Website. Accessed on February 21st, 2003

Flartey KJ, Spaeth GL, WuDunn D, et al. Comparison of the effect of Alphagan 0.2% versus Trusopt 2.0% in combination with beta-blockers [abstract]. Invest Ophthalmol Vis Sci 1998;39:S480.

Maus TL, Nau C, Brubaker RF. Comparison of the early effects of brimonidine and apraclonidine as topical ocular hypotensive agents. Arch Ophthalmol 1999;117:586-91.

Product monograph of E-Pilo. In: Carruthers-Czyewski P, ed. Compendium of Pharmaceuticals and Specialties. 13th, ed. Canadian Pharmaceutical Association. Ottawa, On. 1995.

Repchinsky C, editor. Compendium of Pharmaceuticals and Specialties, 37th Edition. Canadian Pharmacists Association, 2002, Ottawa.

Rafuse P. Glaucoma. Chapter 20. In: Gray J, ed. Therapeutic Choices. 3rd ed. Canadian Pharmacists Association. Ottawa, On. 2000. P. 161-7.

Rafuse P. Glaucoma. Chapter 20. In: Gray J, ed. Therapeutic Choices. 2nd ed. Canadian Pharmacists Association. Ottawa, On. 1998. P. 148-53.

Simmons ST, Earl ML, et al. Three-month comparison of brimonidine and latanoprost as adjunctive therapy in glaucoma and ocular hypertension in patients uncontrolled on â-blockers. Ophthalmology 2002;109:307-15.

Simmons ST, et al. Efficacy of brimonidine 0.2% and dorzolamide 2% as adjunctive therapy to beta-blockers in adult patients with glaucoma or ocular hypertension. Clin Therapeut 2001;23(4);604-19.

Simmons ST, Samuelson TW, et al. Comparison of brimonidine with latanoprost in the adjunctive treatment of glaucoma. Clin Therapeut 2000;22(4):388-99.

Traverso CE, et al. Additivity of brimonidine 0.2% BID or pilocarpine 2.0% TID to beta-blocker monotherapy [abstract]. Invest Ophthalmol Vis Sci 1998;39:S480.

Melamed et al. Ongoing clinical assessment of the safety profile and efficacy of brimonidine compared with timolol: three year results. Clin Therapeut. 2000; 22(1); 103-110.

Katz et al. Brimonidine 0.2% twice daily vs timolol 0.5% twice daily: 1-year results in glaucoma patients. Am.J Opht 1999;127(1);20-26.

Stewart et al. Brimonidine 0.2% versus dorzolamide 2% each given three times daily to reduce intraocular pressure. Am J Opht; 2000;129(6);723-727.

Kampik et al. Intraocular pressure-lowering effects of latanoprost and brimonidine therapy in patients with open-angle glaucoma or ocular hypertension: A randomized observer masked multicenter study. J Glaucoma;2002;11(2);90-96.

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