Report on New Patented Drugs - Avastin
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: Avastin
Generic Name: (bevacizumab)
DIN: 02270994 25 mg/mL injectable solution
Patentee: Hoffmann-La Roche Canada Ltd.
Indication - as per product monograph:
In combination with fluropyrimidine-based chemotherapy is indicated for first-line treatment of patients with metastatic carcinoma of the colon or rectum.
Notice of Compliance: September 9, 2005
Date of First Sale: November 2, 2005
ATC Class: L01XC07
Antineoplastic and Immunomodulating; Antineoplastic Agents; Other Antineoplastic Agents; Monoclonal Antibodies.
Application of the Guidelines
The introductory price of Avastin was 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 in which it was sold.
Avastin is a new active substance and the PMPRB's Human Drug Advisory Panel (HDAP) recommended that Avastin be reviewed as a category 3 new medicine (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.
The HDAP did not recommend any comparators for Avastin (bevacizumab) given that, based on current published evidence, no other drug product appears to be indicated for, or have similar efficacy when used in combination with an irinotecan/fluoropyrimidine chemotherapy, in the first-line treatment of metastatic colorectal cancer (MCRC). Although Avastin provides a significant survival improvement when added to an irinotecan-based fluropyrimidine chemotherapy regimen, the HDAP could not determine whether Avastin provides a significant improvement over existing chemotherapy regimens used for first-line treatment of MCRC, as studies using other known efficacious regimens are not yet publicly available.
Under the Guidelines, the introductory price of 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 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.
As no comparators were identified for the purposes of conducting a TCC test, the price of Avastin was considered within the Guidelines as it did not exceed the median of the international prices identified in an IPC test.
||Price for 25 mg/mL injectable solution
Canada - Hoffmann-La Roche Canada Ltd.
Germany - Rote Liste, July 2005
Italy - L'informatore farmaceutico, December 2005
Sweden - Prislista, September 2005
Switzerland - Medwin Web site, July-December 2005
U.K. - MIMS, December 2005
U.S. - Average of Thomson Micromedex Wholesale Acquisition Cost (WAC),
October 2005 and Federal Supply Schedule (FSS), July-December 2005.
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.
1. Bevacizumab. Caractéristiques du médicament. Commission de la Transparence. France.
2. Chen HX, Mooney M, Boron M, et al. Bevacizumab (BV) plus 5 FU/leucovorin (FU/LV) for advanced colorectal cancer (CRC) that progressed after standard chemotherapies: An NCI treatment referral center trial (TRC-0301). J Clin Oncol 2004; 22(14S):3515 (abstract).
3. Emmanouilides C, Pegram M, Robinson R, et al. Anti-VEGF antibody bevacizumab (Avastin) with 5FU/LV as third line treatment for colorectal cancer. Tech Coloproctol 2004;8:S50-2.
4. European Medicines Agency. Avastin. Clinical efficacy. January 29, 2005. Available at: www.emea.eu.int/humandocs/Humans/EPAR/avastin/avastin.htm
5. Giantonio BJ, Levy D, O'Dwyer PJ, et al. Bevacizumab (anti-VEGF) plus IFL (irinotecan, fluorouracil, leucovorin) as front-line therapy for advanced colorectal cancer (advCRC): Results from the Eastern Cooperative Oncology Group (ECOG) Study E2200. Proc Am Soc Clin Oncol 2003;22:255 (abstract 1024) www.asco.org/ac/1,1003,_12-002636-00_18-0023-00_19-00103603,00.asp (accessed March 29, 2005).
6. Hoff PM. Future directions in the use of antiangiogenic agents in patients with colorectal cancer. Semin Oncol 31(suppl 17):17-21).
7. Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004;350:2335-42.
8. Hurwitz H, Fehrenbacher L, Hainsworth J, et al. Bevacizumab in combination with 5-fluorouracil and leucovorin: A promising regimen for first-line metastatic colorectal cancer. Gastrointestinal Cancers Symposium 2004 (abstract 286). www.asco.org/ac/1,1003,_12-002636-00_18-0027-00_19-00497,00.asp (accessed March 29, 2005).
9. Hurwitz HH et al. Bevacizumab in combination with fluorouracil and leucovorin: an active regimen for first-line metastatic colorectal cancer. J Clin Oncol 2005;23:3502-3508.
10. Iqbal S, Lenz HJ. Angiogenesis inhibitors in the treatment of colorectal cancer. Semin Oncol 31(suppl 17):10-6.
11. Kabbinavar FF et al. Addition of bevacizumab to bolus fluorouracil and leucovorin in first-line metastatic colorectal cancer; results of a randomized Phase II trial. J Clin Oncol 2005;23:1-9.
12. Kabbinavar FF, Schulz J, McCleod M, et al. Bevacizumab (a monoclonal antibody to vascular endothelial growth factor) to prolong progression-free survival in first-line colorectal cancer (CRC) in subjects who are not suitable candidates for first-line CPT-11. J Clin Oncol 2004;22(14S):3516 (abstract).
13. Kabbinavar F, Hurwitz HI, Fehrenbacher L, et al. Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/Leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol 2003;21:60-5.
14. Maroun J, Ng E, Berthelot JM, et al. Lifetime costs of colon and rectal cancer management in Canada. Chronic Dis Can 2003;24:91-101. www.phac-aspc.gc.ca/publicat/cdic-mcc/24-4/c_e.html (accessed March 11, 2005).
15. Mass RD, Fyfe G, Hambleton J, et al. Bevacizumab in combination with 5-FU/leucovorin improves survival in patients with metastatic colorectal cancer: A combined analysis. J Clin Oncol 2004;22(14S):3616 (abstract).
16. Mayer RJ. Two steps forward in the treatment of colorectal cancer. N Engl J Med 2004;350:2406-8.
17. Meyerhardt JA, Mayer RJ. Systemic therapy for colorectal cancer. N Engl J Med 2005;352:476-87.
18. Mitchell EP, Alberts SR, Schwartz MA, et al. High-dose bevacizumab in combination with FOLFOX4 improves survival in patients with previously treated advanced colorectal cancer: Results from the Eastern Cooperative Oncology Group (ECOG) study E3200. 2005 Gastrointestinal Cancers Symposium (abstract 169a). asco.org/asco/publications/abstract_print_view/1,1148,_12-002636-00_18-0036-00_19-0010294,00.html (accessed March 29, 2005).
19. Motl S. Bevacizumab in combination chemotherapy for colorectal and other cancers. Am J Health-Syst Pharm 2005;62:1021-32.
20. National Cancer Institute of Canada. Canadian Cancer Statistics 2004. Toronto: NCIC, 2004. www.ncic.cancer.ca/vgn/images/portal/cit_86751114/14/35/195991821ncic_stats2004_en.pdf (accessed March 14, 2005).
21. Product monograph of Avastin (bevacizumab). Hoffman-La Roche Limited, Mississauga, ON.
22. US National Comprehensive Cancer Network. Practice Guidelines Colon Cancer v.3.2005. Chemotherapy for advanced or metastatic disease.
23. US National Comprehensive Cancer Network. Practice Guidelines Rectal Cancer v.3.2005. Chemotherapy for advanced or metastatic disease.
24. Zondor SD, Medina PJ. Bevacizumab: an angiogenesis inhibitor with efficacy in colorectal and other malignancies. Ann Pharmacother 2004;38:1258-64.