Report on New Patented Drugs – Emend

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

Brand Name: Emend

Generic Name: (aprepitant)

DIN: 02298791 (80 mg capsule)
02298805 (125 mg capsule)
02298813 (1 X 125 mg and 2 X 80 mg capsules)
(tri-pack)

Patentee: Merck Frosst Canada Ltd.

Indication – as per product monograph:

In combination with a 5-HT3 antagonist class of antiemetics and dexamethasone is indicated for the: 1. prevention of acute and delayed nausea and vomiting due to highly emetogenic cancer chemotherapy and 2. prevention of nausea and vomiting in women due to treatment with a moderately emetogenic cancer chemotherapy consisting of cyclophosphamide and anthracycline.

Date of Issuance of First Patent
Pertaining to the Medicine: March 21, 2006

Notice of Compliance: August 24, 2007

Date of First Sale: September 24, 2007

ATC Class: A04AD
Alimentary Tract and Metabolism;
Antiemetics and Antinauseants;
Antiemetics and Antinauseants; Other antiemetics

Application of the Guidelines

Summary

The introductory prices of Emend were found to be within the Guidelines because the prices 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 Emend was sold.

Scientific Review

Emend is a new active substance and the PMPRB's Human Drug Advisory Panel (HDAP) recommended that Emend be reviewed as a category 3 new medicine (provides moderate, little or no therapeutic advantage over comparable existing medicines).

The Therapeutic Class Comparison (TCC) test of the Guidelines provides that the price of a category 3 new medicine cannot exceed the prices of other comparable drugs that treat the same disease or condition. Comparators are generally selected from among existing drug products in the same 4th level of the World Health Organization (WHO) Anatomical Therapeutic Chemical (ATC) classification 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.

The HDAP did not recommend any comparators for the conduct of a TCC test.

Price Review

Under the Guidelines, the introductory price of a category 3 new drug product will be presumed to be excessive if it exceeds the price of all the comparable drug products based on a TCC test or if it exceeds the prices of the same medicine sold in the seven countries listed in the Regulations.

The Guidelines further state that when it is inappropriate or impossible to conduct a TCC test, Board Staff will give primary weight to the median of the international prices identified in an International Price Comparison (IPC) test. See the PMPRB's Compendium of Guidelines, Policies and Procedures for a more complete description of the Guidelines.

It was not possible to conduct a TCC test as the HDAP did not identify any comparator drug products. At introduction, the prices of Emend were within the Guidelines as they did not exceed the median of the international prices identified in an IPC test as shown in the tables below.

Introductory Period (September to December 2007) Emend 80 mg capsule

Emend 125 mg capsule

Emend 80 mg and 125 mg capsules (tri-pack)

Source: Publicly available prices as per the Regulations

The publication of the Summary Reports is part of the PMPRB's commitment to make its price review more transparent.

Where comparators and dosage regimens are referred to in the Summary Reports, they have been selected by 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 PMPRB reserves the right to exclude from the therapeutic class comparison list any drug if it has reason to believe it is being sold at an excessive price.

In its Summary Reports, the PMPRB will also refer to the publicly available prices of comparators provided such prices are not more than 10% above a non-excessive price in which case no price will be made available. As a result, the publication of these prices is for information purposes only and should not be relied upon as being considered within the Guidelines.

The information contained in the PMPRB's Summary Reports should not be relied upon for any purpose other than stated 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 - Emend

1. Aguilar EA, Figueiras MC, Cortes-Funes H, et al. Clinical practice guidelines on antiemetics in oncology. Expert Rev Anticancer Ther 2005;5(6):963-72.

2. British Columbia Cancer Agency. Guidelines for prevention and treatment of chemotherapy-induced nausea and vomiting in adults. Revised November 1, 2005. www.bccancer.bc.ca/NR/rdonlyres/8E898B5D-3F12-4623-8E32-5B3C429C58F7/10717/SCNAUSEA1Nov06.pdf

3. Campos D, Rodrigues Pereira J, Reinhardt RR, et al. Prevention of cisplatin-induced emesis by the oral neurokinin-1 antagonist, MK-869, in combination with granisetron and dexamethasone or with dexamethasone alone. J Clin Oncol 2001;19:1759-1767.

4. Cancer Care Nova Scotia. Guidelines for the management of nausea and vomiting in cancer patients. January 2004. www.cancercare.ns.ca/media//documents/NauseaVomitingFullVersion.pdf

5. Cancer Care Ontario. Management of chemotherapy-induced nausea and vomiting. Revised April 2004. www.cancercare.on.ca/pdfchemo/NVguidelines.pdf

6. Chawla SP, Grunberg SM, Gralla RJ, et al. Establishing the dose of the oral NK1 antagonist aprepitant for the prevention of chemotherapy-induced nausea and vomiting. Cancer 2003;97:2290-300.

7. Dando TM, Perry CM. Aprepitant. A review of its use in the prevention of chemotherapy-induced nausea and vomiting. Drugs 2004;64:777-94.

8. de Wit R, Herrstedt J, Rapoport B, et al. Addition of the oral NK1 antagonist aprepitant to standard antiemetics provides protection against nausea and vomiting during multiple cycles of cisplatin-based chemotherapy. J Clin Oncol 2003;21:4105-11.

9. de Wit R, Herrstedt J, Rapoport B, et al. The oral NK1 antagonist, aprepitant, given with standard antiemetics provides protection against nausea and vomiting over multiple cycles of cisplatin-based chemotherapy: a combined analysis of two randomised, placebo-controlled phase III clinical trials. Eur J Cancer 2004;40:403-10.

10. Gralla RJ, de Wit R, Herrstedt J, et al. Antiemetic efficacy of the neurokinin-1 antagonist, aprepitant, plus a 5HT3 antagonist and a corticosteroid in patients receiving anthracyclines or cyclophosphamide in addition to high-dose cisplatin. Cancer 2005;104:864-8.

11. Grote T, Hajdenberg J, Cartmell A, et al. Combination therapy for chemotherapy-induced nausea and vomiting in patients receiving moderately emetogenic chemotherapy: palonosetron, dexamethasone, and aprepitant. J Support Oncol 2006;4:403-8.

12. Herrstedt J, Muss HB, Warr DG, et al. Efficacy and tolerability of aprepitant for the prevention of chemotherapy-induced nausea and emesis over multiple cycles of moderately emetogenic chemotherapy. Cancer 2005;104:1548-55.

13. Hesketh PJ, Grunberg SM, Herrstedt J, et al. Combined data from two phase III trials of the NK1 antagonist aprepitant plus a 5HT3 antagonist and a corticosteroid for prevention of chemotherapy-induced nausea and vomiting: effect of gender on treatment response. Support Care Cancer 2006;14:354-60.

14. Hesketh PJ, Grunberg SM, Gralla RJ, et al. The oral neurokinin-1 antagonist aprepitant for the prevention of chemotherapy-induced nausea and vomiting: a multinational, randomized, double-blind, placebo-controlled trial in patients receiving high-dose cisplatin – The aprepitant protocol 052 study group. J Clin Oncol 2003;21:4112-9.

15. Kris MG, Hesketh PJ, Herrstedt J, et al. Consensus proposals for the prevention of acute and delayed vomiting and nausea following high-emetic-risk chemotherapy. Support Care Cancer 2005;13:85-96.

16. Kris MG, Hesketh PJ, Somerfield MR, et al. American Society of Clinical Oncology guideline for antiemetics in oncology: update 2006. J Clin Oncol 2006;24:2932-47.

17. Kris MG, Hesketh PJ, Somerfield MR, et al. American Society of Clinical Oncology guideline for antiemetics in oncology: update 2006. J Clin Oncol 2006;24:2932-47.

18. Kris MG. Why do we need another antiemetic? Just ask. J Clin Oncol 2003;21:4077-80.

19. Massaro AM, Lenz KL. Aprepitant: a novel antiemetic for chemotherapy-induced nausea and vomiting. Ann Pharmacother 2005;39:77-85.

20. Moore S, Tumeh J, Wojtanowski S, et al. Cost-effectiveness of aprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with highly emetogenic chemotherapy. Value Health 2007;10:23-31.

21. National Comprehensive Cancer Network. Antiemesis. V.I.2007. www.nccn.org/professionals/physician_gls/PDF/antiemesis.pdf

22. Navari RM, Reinhardt RR, Gralla RJ, et al. Reduction of cisplatin-induced emesis by a selective neurokinin-1-receptor antagonist. N Engl J Med 1999;340:190-5.

23. Oechsle K, Müller MR, Hartmann JT, et al. Aprepitant as salvage therapy in patients with chemotherapy-induced nausea and emesis refractory to prophylaxis with 5-HT3 antagonists and dexamethasone. Onkologie 2006;29:557-61.

24. Osoba D, Zee B, Warr D, et al. Effect of postchemotherapy nausea and vomiting on health-related quality of life. Support Care Cancer 1997;5:307-13.

25. Osorio-Sanchez JA, Karapetis C, Koczwara B. Efficacy of aprepitant in management of chemotherapy-induced nausea and vomiting. Intern Med J 2007;37:247-50.

26. Poli-Bigelli S, Rodrigues-Pereira J, Carides AD, et al. Addition of the neurokinin 1 receptor antagonist aprepitant to standard antiemetic therapy improves control of chemotherapy-induced nausea and vomiting. Cancer 2003;97:3090-8.

27. Schmoll HJ, Aapro MS, Poli-Bigelli S, et al. Comparison of an aprepitant regimen with a multiple-day ondansetron regimen, both with dexamethasone, for antiemetic efficacy in high-dose cisplatin treatment. Ann Oncol 2006;17:1000-6.

28. Van Belle S, Lichinitser MR, Navari RM, et al. Prevention of cisplatin-induced acute and delayed emesis by the selective neurokinin-1 antagonists, L-758,298 and MK-869. Cancer 2002;94:3032-41.

29. Warr D, Oliver T, et al. The role of neurokinin-1 receptor antagonists in the prevention of emesis due to high-dose cisplatin: a clinical practice guideline. Cancer Care Ontario evidence-based series #12-4: section 1. April 5, 2005. www.cancercare.on.ca/pdf/pebc12-4f.pdf

30. Warr D. The neurokinin1 receptor antagonist aprepitant as an antiemetic for moderately emetogenic chemotherapy. Expert Opin Pharmacother 2006;7:1653-8.

31. Warr DG, Grunberg SM, Gralla RJ, et al. The oral NK1 antagonist aprepitant for the prevention of acute and delayed chemotherapy-induced nausea and vomiting: pooled data from 2 randomised, double-blind, placebo controlled trials. Eur J Cancer 2005;41:1278-85.

32. Warr DG, Hesketh PJ, Gralla RJ, et al. Efficacy and tolerability of aprepitant for the prevention of chemotherapy-induced nausea and vomiting in patients with breast cancer after moderately emetogenic chemotherapy. J Clin Oncol 2005;23:2822-30.