Report on New Patented Drugs - Sensipar

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.

Sensipar

Brand Name: Sensipar

Generic Name: (cinacalcet hydrochloride)

DIN:

02257130 30 mg tablet
02257149 60 mg tablet
02257157 90 mg tablet

Patentee: Amgen Canada Inc.

Indication - as per product monograph:

For the treatment of secondary hyperparathyroidism in patients with Chronic Kidney Disease (CKD)

Notice of Compliance: August 9, 2004

Date of First Sale: September 29, 2004
The first patent pertaining to Sensipar was issued on August 30, 2005 and it came under the PMPRB's jurisdiction at that time.

ATC Class: H05BX01
Systemic Hormonal Preparations Excluding Sex Hormones and Insulins, Calcium Homeostasis, Anti-parathyroid Hormones

Application of the Guidelines

Summary

The introductory prices of Sensipar 30 mg and 60 mg tablets were found to be within the Guidelines because the price in Canada did not exceed the median of the prices of the same drug in those countries listed in the Patented Medicines Regulations (Regulations) in which they were sold or did not do so by an amount sufficient to trigger any of the investigation criteria under the Compliance & Enforcement Policy. The introductory price of Sensipar 90 mg tablet exceeded the median of the prices of the same drug in those countries listed in the Regulations in which it was sold in the introductory period. However, its price was considered within the Guidelines in the subsequent reporting period.

Scientific Review

Sensipar is a new active substance and the PMPRB's Human Drug Advisory Panel (HDAP) recommended that Sensipar be reviewed as a category 2 new medicine (breakthrough or substantial improvement) as it provides a substantial improvement in the treatment of secondary hyperparathyroidism in patients with Chronic Kidney Disease (CKD) where the current standard of care is insufficient to control parathyroid hormone (PTH) levels because there is currently a lack of effective therapy for patients who do not meet the National Kidney Foundation Disease Outcome Quality Indicators; failure to meet these indicators has been shown to result in morbidity and mortality.

The HDAP did not identify any comparators for the conduct of a Therapeutic Class Comparison (TCC) Test.

Price Review

Under the Guidelines, the introductory price of a new category 2 drug product will be presumed to be excessive if it exceeds the prices of all comparable drug products, based on a TCC Test, and the median of the international prices identified in an International Price Comparison (IPC) Test.

As no comparable drug products were identified for purposes of conducting a TCC Test, the introductory prices were reviewed based on the median of the IPC Test. When Sensipar was first sold in 2004, the price of the 30 mg tablet was within the Guidelines; the price of the 60 mg was considered within the Guidelines as its price did not exceed the MNE price by a margin which would trigger the investigation criteria; and the price of the 90 mg tablet exceeded the MNE price by a margin which would have triggered the criteria for commencing an investigation. The price of the 90 mg tablet was considered within the Guidelines in the following reporting period.

Source: Publicly available prices as per the Patented Medicines Regulations

The Guidelines provide that when a medicine is sold in fewer than five countries at the time of its introduction, the introductory price will be treated as the interim benchmark price. The interim benchmark price may be reviewed at the end of three years or when the medicine is sold in at least five countries, whichever comes first.

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 – Sensipar

1. Anon. Cinacalcet (Sensipar). Med Let 2004;46(1192):80.

2. Block GA. The impact of calcimimetics on mineral metabolism and secondary hyperparathyroidism in end-stage renal disease.Kidney International 2003;64(87 Suppl):S131-6.

3. Block GA, Goodman WG. Cinacalcet for secondary hyperparathyroidism in hemodialysis recipients [author reply]. N Engl J Med 2004;351:2:189.

4. Block GA, Martin KJ, Turner SA, et al. Phase 3 study results demonstrate efficacy and safety of the calcimimetic cinacalcet HCl in hemodialysis patients with secondary hyperparathyroidism (HPT). Abstract SA-PO743. Available from: www.sensipar.com/downloads/clinical_literature/Block_NAPhase3Study.pdf (Accessed 4 Jan 2005).

5. Block GA, Martin KJ, de Francisca ALM, et al. Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis. N Engl J Med 2004;350:15:1516-25.

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7. Cunningham J. Achieving therapeutic targets in the treatment of secondary hyperparathyroidism. Nephrol Dial Transplant 2004;19 (Suppl 5):v9-v14.

8. Cunningham J et al. Abstract. The effect of cinacalcet HCl on parathyroidectomy, fracture, hospitalization, and mortality in dialysis subjects with secondary hyperparathyroidism.

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13. Goodman WG. The consequences of uncontrolled secondary hyperparathyroidism and its treatment in chronic kidney disease. Seminars Dialysis 2004;17(3): 209-16.

14. Goodman WG. Calcimimetic agents and secondary hyperparathyroidism: rationale for use and results from clinical trials. Pediatr Nephrol 2003;18:1206-10.

15. Goodman WG, Fadda GZ, Finkelstein FO, et al. Cinacalcet HCL is an effective primary therapy for the management of secondary hyperparathyroidism (HPT). Abstract SA-PO741. Available from: www.sensipar.com/downloads/clinical_literature/Goodman_ConcomitantMeds.pdf (Accessed 4 Jan 2005).

16. Goodman WG, Hladik GA, Turner SA, et al. The calcimimetic agent AMG 073 lowers plasma parathyroid hormone levels in hemodialysis patients with secondary hyperparathyroidism. J Am Soc Nephrol 2002;13:1017-24.

17. Harris RZ, Padhi D, Marbury TC, et al. Pharmacokinetics, pharmacodynamics, and safety of cinacalcet hydrochloride in hemodialysis patients at doses up to 200 mg once daily. Am J Kidney Dis 2004;44:1070-6.

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19. K/DOQI. K/DOQI Clinical Practice Guidelines on Bone Metabolism and Disease in Chronic Kidney Disease. Available from: www.kidney.org/professionals/kdoqi/guidelines_bone/index.htm (Accessed 5 January 2005).Guidelines 8a and 8b from this site accessed by PMPRB staff January 14, 2005.

20. Lindberg JS, Culleton B, Wong G, et al. Phase 3 experience with cinacalcet HCL in hemodialysis and peritoneal dialysis patients with secondary hyperparathyroidism (Poster SA-PO752). Presented at: American Society of Nephrology Renal Week, San Diego, CA. November 12-17, 2003.

21. Lindberg JS, Moe SM, Goodman WG, et al. The calcimimetic AMG 073 reduces parathyroid hormone and calcium x phosphorus in secondary hyperparathyroidism. Kidney Internat 2003;63:248-54.

22. Malluche HH. Abstract. Cinacalcet HCl reduces bone turnover and bone marrow fibrosis in hemodialysis patients with secondary hyperparathryoidism.

23. Mansour J, Benyahia M, Harboucher L, et al. Calcimetic AMG 073 at 50 and 100 mg per day. Kidney International 2003;64(5):2324-5.

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26. Moe SM, Sprague SM, Cunningham J, et al. Long-term treatment of secondary hyperparathyroidism (HPT) with the calcimimetic cinacalcet HCl. Abstract SA-PO753. Available from: www.sensipar.com/downloads/clinical_literature/Moe_KDOQIGoals.pdf (accessed 4 Jan 2005).

27. Nemeth EF, Heaton WH, Miller M, et al. Pharmacodynamics of the type II calcimimetic compound cinacalcet HCl. J Pharmacol Experiment Ther 2003;308(2):627-35.

28. National Institute for Clinical Excellence. Proposed Health Technology Appraisal – cinacalcet HCl for the treatment of hyperparathyroidism secondary to impaired renal function. Draft Scope. Available from: www.nice.org.uk/page.aspx?o=220597 (Accessed 5 Jan 2005).

29. Ohashi N, Uematsu T, Nagashima M, et al. The calcimimetic agent KRN 1493 lowers plasma hormone and ionized calcium concentrations in patients with chronic renal failure on haemodialysis both on the day of haemodialysis and on the day without hemodialysis. Br J Clin Pharmacol;57(6):726-34.

30. Owda AK, Alam MG, Kumar J. Cinacalcet for secondary hyperparathyroidism in hemodialysis recipients [letter]. N Engl J Med 2004;351:2:188.

31. Personal communication with Marie Josee Deschenes, clinical pharmacist (Nephrology Service). Ottawa Hospital, General Campus. 7 January 2005.

32. Product Monograph of Sensipar (cinacalcet hydrochloride) Amgen Canada Inc. Mississauga, ON. August 17, 2004.

33. Stamatakis MK. Chronic Kidney Disease. In: Pharmacotherapy Self-Assessment Program. Book 9 – Pediatrics, Nephrology. 4th ed. American College of Clinical Pharmacy. Kansas City, MO. 2003. P. 175-85.

34. Quarles LD, Sherrard DJ, Adler S, et al. The calcimimetic AMG 073 as a potential treatment for secondary hyperparathyroidism of end-stage renal disease. J Am Soc Nephrol 2003;14:575-83.

35. Quarles LD, Zeig S, Speigel DM, et al. Cinacalcet HCl controls secondary hyperparathyroidism (PT) in dialysis patients regardless of disease severity. Abstract SA-PO751. Available from: www.sensipar.com/downloads/clinical_literature/Quarles_DiseaseSeverity.pdf (Accessed 4 Jan 2005).

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38. The Kidney Foundation of Canada. Facing the Facts. Winter 2004. Available from: www.kidney.ca/english/march/pdfs/FacingFacts.pdf (Accessed 7 Jan 2005).

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43. WHO Collaborating Centre for Drug Statistics Methadology. New ATC Codes and DDDs. [database online]. Available from: www.whocc.no/atcddd/new_atc_ddd.html (accessed 23 Dec 2004).