Report on New Patented Drugs - Ebixa

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: Ebixa

Generic Name: memantine hydrochloride

DIN: 02260638 10 mg tablet

Patentee: Lundbeck Canada

Indication - as per product monograph: For the symptomatic treatment of patients with moderate to severe dementia of the Alzheimer's type.

Notice of Compliance: December 8, 2004

Date of First Sale: March 3, 2004

ATC Class: N06DX01
Nervous System; Psychoanaleptics: Anti-Dementia Drugs; Other Anti-Dementia Drugs

Application of the Guidelines

Summary:

The introductory price of Ebixa 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 Ebixa is sold.

Scientific Review:

The PMPRB's Human Drug Advisory Panel (HDAP) recommended that Ebixa 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. The Guidelines provide that it may, however, be appropriate to include products from other ATC classes if they are clinically equivalent to the appropriate indication of 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.

Alzheimer's disease is the most common form of dementia in the elderly. The classic clinical features of Alzheimer's disease are amnesic type of memory impairment, deterioration of language, behavioral disturbances and visuospatial deficits. Motor and sensory abnormalities, gait disturbances and seizures are more prevalent in later stages of the disease.

Ebixa (memantine) is the first of a new class of medications for Alzheimer's disease with a different mechanism of action than current medicines. The only other agent that falls within the same 4th level ATC class is ginko bilboa. It is not indicated for the treatment of Alzheimer's disease, nor is there any evidence supporting such use. The HDAP recommended the following five agents which are available on the Canadian market and are indicated or used in the treatment of Alzheimer's disease: Aricept (donepezil), Reminyl, (galantamine), Exelon (rivastigmine), Selegiline (selegiline hydrochloride) and Vitamin E (D-alpha tocopheryl).

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

1 Publicly available price as per the Patented Medicines Regulations
2 ODB, January 2003, as of Update E, November 2004, no price change
3 Liste de Médicaments, Régie de l'assurance maladie du Québec, 15th edition, as of update 7, November 2004, no price change
4 Shoppers Drug Mart Retail Price, December 2004

In 2004, Ebixa was also being sold in France, Germany, Sweden, Switzerland, 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 price of Ebixa in Canada was the 4th lowest of those countries, below the median international price.

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/References Considered by the HDAP

1. http://www.hc-sc.gc.ca/pphb-dgspsp/publicat/cdic-mcc/19-4/e_e.html

2. Whipple Guthrie E. The use of memantine (Namenda) in patients with mild-to-moderate Alzheimer's disease. Pharmacist Letter 2004;20(200202).

3. Feret B, Dicks R. Memantine: an oral NMDA antagonist for the treatment of moderate-to-severe Alzheimer's disease. Formulary 2004;39:91-103.

4. Cada DJ, Levien T, Baker DE. Memantine. Hosp Pharm 2004;39(3):254-63.

5. Cummings JL. Alzheimer's disease. N Engl J Med 2004;351(1):56-67.

6. Reisberg B, Doody R, Stoffler A, et al. Memantine in moderate-to-severe Alzheimer's disease. N Engl J Med 2003;348(14):1333-41.

7. Wimo A, Winblad B, Stoffler A, Wirth Y, Mobius HJ. Resource utilisation and cost analysis of memantine in patients with moderate to severe Alzheimer's disease. Pharmacoeconomics 2003;21(5):327-40.

8. Rive B, Vercelletto M, Dalmarre Damier F, Cochran J, Francois C. Memantine enhances autonomy in moderate to severe Alzheimer's disease. Int J Geria Psych 2004;19:458-64.

9. Ferris S, Schmitt F, Doody R. Long-term treatment with the NMDA antagonist memantine: Results of a 24-week, open-label extension study in moderate to severe Alzheimer's disease. Poster presented at the 16th Annual Meeting of the American Association of Geriatric Psychiatry. May 2003, Honolulu, Hawaii. http://www.ebixa.ch/de/serveattachment/c114c94d8738096a3319102e37ff3fa1/
longterm_ferris.pdf

10. Tariot RN, Farlow MR, Grossberg GT, Graham SM, McDonald S, Gergel I. Memantine treatment in patients with moderate to severe Alzheimer's disease already receiving donepezil: a randomized controlled trial. JAMA 2004;291(3):317-24.

11. Winbland B, Poritis N. Memantine in severe dementia: results of the 9M-BEST study (benefit and efficacy in severely demented patients during treatment with memantine). Int J Geriat Psych 1999;14:135-46.

12. Wilcock G, Mobius HJ, Stoffer A. A double-blind, placebo-controlled multicentre study of memantine in mild to moderate vascular dementia (MMM500). Int Clin Psychopharmacol 2002;17:297-305.

13. Orgogozo JM, Rigaud AS, Stoffler A, Mobius HJ, Forette F. Efficacy and safety of memantine in patients with mild to moderate vascular dementia: a randomized, placebo-controlled trial (MMM300). Stroke 2002;33:1834-9.

14. Sahin K, Stoeffer A, Furuna P, Rosenwald D, Moebius HJ. Dementia severity and the magnitude of cognitive benefit by memantine treatment. A subgroup analysis of two placebo-controlled clinical trials in vascular dementia. Neurobiology of Aging 2000;21(1S):S168

15. Hartmann S, Mobius HJ. Tolerability of memantine in combination with cholinesterase inhibitors in dementia therapy. Int Clin Psychopharmacol 2003;18:81-5.

16. Anon. Namenda (Memantine HCL) mild to moderate alzheimer's disease studies reported today, Forest Laboratories to seek approval for mild to moderate indication by mid-year. http://www.namenda.com/pdf/PositiveMD-10_1-7_FINAL.pdf

17. Peck P. Memantine may be effective for mild to moderate Alzheimer's disease. http://www.medscape.com/viewarticle/483887

18. Dooby RS, Stevens JC, Beck C, et al. Practice parameter: management of dementia (an evidence-based review: Report of the quality standards subcommittee of the American Academy of Neurology. http://www.neurology.org/cgi/reprint/56/9/1154.pdf

19. Guidance on the use of donepezil, rivastigmine and galantamine for the treatment of Alzheimer's disease. NICE Technology Appraisal Guidance No 19. January 2001. http://www.nice.org.uk/pdf/ALZHEIMER_full_guidance.pdf

20. Sano M, Ernesto C, Thomas RG, et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment of Alzheimer's disease. N Engl J Med 1997;336:1216-22.

21. Product mongraph of Ebixa (memantine hydrochloride). Lundbeck Canada Inc., Montreal, Quebec, June 20, 2003.