Report on New Patented Drugs – Zavesca

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: Zavesca

Generic Name: miglustat

DIN: 02250519 100 mg/capsule

Patentee: Actelion Pharmaceuticals Canada Inc.

Indication - as per product monograph: For the treatment of adult patients with mild to moderate Type 1 Gaucher disease for whom enzyme replacement therapy is not a therapeutic option (e.g. allergy, hypersensitivity, poor venous access, etc)

Notice of Compliance: March 31, 2004

Date of First Sale: May 26, 2004

ATC Class: A16AX06
Alimentary Tract and Metabolism; Other Alimentary Tract and Metabolism Products; Various Alimentary Tract and Metabolism Products

APPLICATION OF THE GUIDELINES

Summary:

The introductory price of Zavesca 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 Zavesca is sold.

Scientific Review:

The PMPRB's Human Drug Advisory Panel (HDAP) recommended that Zavesca 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 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.

Zavesca is a new oral active substance intended for use in the treatment of Type 1 Gaucher disease, an autosomal recessive inherited disorder. Gaucher disease is a lipid storage disorder resulting from a deficiency in the enzyme glucocerebrosidase (glucosylceramidase). Type 1 Gaucher disease, the most common form, does not directly involve the nervous system. There is no cure.

The HDAP recommended Cerezyme (imiglucerase) as the most appropriate comparator for Zavesca. Although this agent is not in the same 4th level ATC class, it shares the same indication and is clinically equivalent at addressing the approved indication.

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 Zavesca and the comparator 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.

As shown in the following table, the price of Zavesca 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 AQPP, October 2004
2 Publicly available prices as per the Patented Medicines Regulations

In 2004, Zavesca was also sold in 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 those countries; the price in Canada of Zavesca was the lowest.

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 considered by the HDAP

1. Heitner R et al. Low-dose N-Butyldeoxynojirimycin (OGT 918) for Type 1 Gaucher Disease. Blood Cells, Molecules Dis 2002;28:127-133.

2. Cox T et al. Novel oral treatment of Gaucher´s disease with N-butyldeoxynojirimycin (OGT 918) to decrease substrate biosynthesis. Lancet 2000;355:1481-1485.

3. Lachman RH, Platt FM. Substrate reduction therapy for glycosphingolipid storage disorder. Exp. Opin. Invest. Drugs 2001;10:455-466.

4. Pastores GM et al. A neurological symptom survey of patients with type I Gaucher disease. J Inherit Metab Dis 2003;26:641-645.

5. Cerezyme. Canadian Prescribing Information (French). Genzyme Therapeutics, 1998

6. Cerezyme. US Prescribing Information. Genzyme Corp. 2003.

7. WHO Collaborating Centre for Drug Statistics Methodology. ATC Index 2004. Available from: http://www.whocc.no/atcddd/

8. Health Canada. Drug Product Database. Available from: http://search.hc-sc.gc.ca/cgi-bin/query?mss=hc/dpd/english/active/simple

9. Repchinsky C, ed. Compendium of Pharmaceuticals and Specialties. Canadian Pharmacists Association. Ottawa, ON. 2004.

10. Product Monograph of Zavesca (miglustat). Actelion Pharmaceuticals Canada Ltd. Laval, PQ. March 30, 2004.

11. Enderlin C, Vogel R, Conaway P. Gaucher Disease. AJN 2003;103(12):50-60.

12. Mankin HJ, Rosenthal DI, Xavier R. Current concepts review: Gaucher Disease. J Bone Joint Surg 2001;83A(5):748-62.

13. McCormack PL, Goa KL. Miglustat. Drugs 2003;63(22):2427-34.

14. Hussar DA. New Drugs of 2003. J Am Pharm Assoc 2004;44(2):168-206.

15. Zimran A, Hollak C, Aerts J, et al. Efficacy and tolerability of N-Butyleoxynojirimycin (OGT 918) in adult patients with type 1 Gaucher disease: Long-term follow-up. Blood 2001;92(11 Suppl 2):26b.

16. The Advisory Council to the European Working Group on Gaucher Disease. The role of the iminosugar N-butyldeoxynojirimycin (miglustat) in the management of type 1 (non-neuronopathic) Gaucher disease: A position statement. J Inherit Metab Dis 2003;26:513-26.

17. Moyses C. Substrate reduction therapy: clinical evaluation in type 1 Gaucher disease. Phil Trans R Soc Lond B 2003;358:955-60.

18. Zimran A, Elstein D. Gaucher disease and the clinical experience with substrate reduction therapy. Phil Trans R Soc Lond B 2003;358:961-66.

19. Anon. Erratum. Blood Cells Molecul Dis 2002;28(2):301.

20. EMEA. Scientific Discussion – Zavesca.2003. Available from: www.emea.eu.int/humandocs/PDFs/EPAR/zavesca/379502en6.pdf.