Report on New Patented Drugs – Axert

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.

Brand Name: Axert

Generic Name: almotriptan

DIN: 02248128 6.25 mg tablet

02248129 12.5 mg tablet

Patentee: Janssen-Ortho Inc.

Indication - as per product monograph:

For the acute treatment of migraine with or without aura in adults.

Notice of Compliance: September 29, 2003

Date of First Sale: January 9, 2004

ATC Class: N02CC05

Nervous system, Analgesics, Antimigraine Preparations, Selective Serotonin (5HT1) Agonists, Almotriptan.

Application of the Guidelines

Summary:

The introductory prices of the Axert drug products 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 Axert is sold.

Scientific Review:

The PMPRB's Human Drug Advisory Panel (HDAP) recommended that Axert be reviewed as a category 3 new drug product (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.

Migraine is characterized by severe headaches accompanied by chronic head pain, nausea, vomiting, and photophobia. The exact mechanism of migraines still remains not fully understood, however, they are thought to be caused by alterations in the activity of serotonin 5-hydoroxytyptamine (5-HT).

Axert is a selective 5-HT1 receptor agonist and belongs to a group of drugs also know as “triptans”. The HDAP identified four agents in the same 4th level ATC that are indicated for the treatment of acute of migraine with or without aura in adults, Imitrex (sumatriptan), Amerge (naratriptan), Maxalt (rizatriptan) and Zomig (zolmitriptan).

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 Axert and the comparators are based on the respective product monographs and supported by clinical literature.

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 introductory prices of Axert were within the Guidelines as the daily cost of therapy did not exceed the cost of therapy with the comparator medicines.

1 Price filed by Janssen-Ortho Inc.
2 Association québécoise des pharmaciens propriétaires (AQPP), October 2003
3 Liste de médicaments, Régie de l'assurance maladie du Québec, October 2003

Amerge and Zomig are not included in the TCC for Axert 12.5 mg. Amerge and Zomig are not available at a higher strength, only as 2.5 mg tablets. The above TCC shows that the market for the triptan drug products is one where although many of the drugs are available in two strengths, all drugs are priced at the same level regardless of strength.

At the time of introduction, Axert 6.25 mg was also being sold in the United States and Axert 12.5 mg was sold in six of the seven countries, including France, Germany, Italy, Sweden, 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 Axert 6.25 mg was lower than the price in the United States, and the price of Axert 12.5 mg was the second highest of the six countries in which it was sold, above the median international price.

The comparators and dosage regimen referred to in the Summary Report have been selected by Board 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. This publication is also part of the PMPRB's commitment to make its price review process more transparent.

The information contained in the PMPRB's Summary Report 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/References:

1. Product monograph of Axert (almotriptan malate). Janssen-Ortho Inc., Toronto, ON, September 22, 2003.

2. Spierings ELH, Gomez-Mancilla B, Grosz DE, et al. Oral almotriptan vs oral sumatriptan in the abortive treatment of migraine. Arch Neurol 2001;58(6):944-50.

3. Dowson AJ, Massiou H, Lainez JM, Cabarrocas X. Almotriptan is an effective and well-tolerated treatment for migraine pain: results of a randomized, double-blind, placebo-controlled clinical trial. Cephalalgia 2002;22:453-61.

4. Colman SS, Brod MI, Krishnamurthy A, et al. Treatment statisfaction, functional status, and health-related quality of life of migraine patients treated with almotriptan or sumatriptan. Clinical Therapeutics 2001;23(1) :127-45.

5. Leira R, Dualde E, del Barrio H, et al. Almotriptan versus rizatriptan in patients with migraine in spain. Headache 2003;43 :734-41.

6. Pascual J, Falk RM, Piessens F, et al. Consitent efficacy and tolerability of almotriptan in the acute treatment of multiple migraine attacks: results of a large, randomized, double-blind, placebo-controlled study. Cephalagia 2000;20 :588-96.

7. Dahlof C, Tfelt-Hanssen P, Massiou H, et al. Dose finding, placebo-controlled study of oral almotriptan in the acute treatment of migraine. Neurology 2001;57 :1811-7.

8. Cabarrocas X, Esbri R, Peris F, Ferrer P. Long-term efficacy and safety of oral almotriptan : interim analysis of a 1-year open study. Headache 2001;41:57-62.

9. Cabarrocas X. Efficacy and tolerability of subcutanous almotriptan for the treatment of acute migraine: a randomized, double-blind, parallel-group, dose-finding study. Clinical Therapeutics 2001;23(11) :1867-75.

10. Dodick DW. Oral almotriptan in the treatment of migraine: safety and tolerability. Headache 2001;41 :449-55.

11. Mathew NT. Use of rescue medication in trials of almotriptan versus placebo in the treatment of acute migraine. Clinical Therapeutics 2002;24(4) :520-9.

12. Dodick DW. Almotriptan increases sustained pain-free outcomes in acute migraine: results from three controlled clinical trials. Headache 2002;42 :21-7.

13. Mathew NT. Almotriptan increases pain-free status in patients with acute migraine treated in placebo-controlled clinical trials. Headache 2002;42(suppl 1) :S32-7.

14. Pascual J, Cabarrocas X. Within-patient early versus delayed treatment of migraine attacks with almotriptan: the sooner the better. Headache 2002;42 :28-31.

15. Mathew NT. A long-term open-label study of oral almotriptan 12.5 mg for the treatment of acute migraine. Headache 2002;42 : 32-40.

16. Ferrari MD, Goadsby PJ, Roon KI, Lipton RB. Triptans (serotonin, 5-HT1B/1D agonists) in migraine: detailed results and methods of a meta-analysis of 53 trials. Cephalagia 2002;22:633-58.

17. Mondell BE. A review of the effects of almotriptan and other triptans on clinical trial outcomes that are meaningful to patients with migraine. Clinical Therapeutics 2003;25(2):331-41.

18. Dahlof CGH, Dodick D, Dowson AJ, Pascual J. How does almotriptan compare with other triptans? A review of data from placebo-controlled clinical trials. Headache 2002;42:99-113.

19. Adelman JU, Belsey J. Meta-analysis of oral triptan therapy for migraine: number needed to treat and relative cost to achieve relief within 2 hours. JMCP 2003;9(1):45-52. (hard copy)

20. Cada DJ, Levien T, Baker DE. Almotriptan malate. Hosp Pharm 2001;36(10):1066-75.

21. Balbisi EA. Efficacy and safety of almotriptan malate for migraine. Am J Health-Syst Pharm 2002;59:2184-93.

22. Keam SJ, Goa KL, Figgitt DP. Almotriptan; a review of its use in migraine. Drugs 2002;62(2):387-414.

23. Snow V, Weiss K, Wall EM, et al. Pharmacologic management of acute attacks of migraine and prevention of migraine headache. Ann Intern Med 2002;137:840-9.

24. Rothermich EA, Levaux HP, Colman SC, Rowland CR, Gomez-Mancilla B. Costs minimization analysis of almotriptan versus sumatriptan for the acute treatment of moderate to severe migraine headache. ASHP-Midyear Clinical Meeting, December 2000. Abstract from International Pharmaceutical Abstracts Online.

25. Wang JT, Barr CE, Torigoe Y, et al. Costs savings in migraine associated with less chest pain on new triptan therapy. Am J Managed Care 2002;8(suppl 3):S102-7 (abstract).

26. Mannix LK, Adelman JU, Goldfarb SD, et al. Almotriptan versus sumatriptan in migraine treatment: direct medical costs of managing adverse chest symptoms. Am J Managed Care 2002;8(suppl 3):S94-101 (abstract).