Reports on New Patented Drugs - Pegasys
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: Pegasys
Generic Name: peginterferon alfa-2a injection
DIN: 02248077 pre-filed syringe (180 mcg / 0.5mL)
02248078 single-use vial (180 mcg / 1mL)
Patentee: Hoffmann-La Roche Limited
Indication - as per product monograph:
For the treatment of chronic hepatitis C in adult patients without cirrhosis and in adult patients with compensated cirrhosis.
Notice of Compliance: August 13, 2003
Date of First Sale: August 14, 2003
ATC Class: L03AB11
Cytokines and Immunomodulators - Interferons
APPLICATION OF THE GUIDELINES:
The introductory prices of Pegasys were 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 introductory prices of Pegasys did not exceed the range of prices in other comparator countries where Pegasys was sold.
Pegasys is a new active substance and the PMPRB´s Human Drug Advisory Panel (HDAP) recommended that Pegasys 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 PMPRB´s Price 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.
Although there are a number of other medicines in the same 4th level ATC class only Roferon (interferon alfa-2a), Intron A (interferon alfa-2b), and Unitron (peginterferon alfa-2b) share the same indication as Pegasys. The HDAP identified Unitron as the most appropriate comparable medicine, as like Pegasys, it is a pegylated interferon.
The Guidelines provide that the dosage recommendation for comparison purposes will normally not be higher than the maximum of the usual recommended dosage. The recommended comparable dosage regimens for Pegasys and the comparator are based on the respective product monographs and supported by clinical literature.
Under the PMPRB´s Price Guidelines, the introductory price of a new category 3 drug product will be presumed to be excessive if it exceeds the prices 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 (Regulations). The introductory prices of Pegasys were within the PMPRB´s Price Guidelines as they did not exceed the cost of therapy with the comparator medicine.
||Cost Per Week
||180 mcg / week
||1.5 mcg / kg / week
||180 mcg / week
||1.5 mcg / kg / week
1 PPS Pharma, January 2004
2 Liste de médicaments, Régie de l´assurance maladie du Québec, October 2003
In 2003, Pegasys pre-filled syringe was being sold in all of the countries listed in the Regulations and Pegasys single use vial was being sold in Italy, Sweden, Switzerland and the United States. In compliance with the PMPRB´s Price Guidelines, the introductory prices of Pegasys in Canada did not exceed the range of prices in those countries; the prices of Pegasys in Canada were the second highest, above 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.
References – Pegasys
1. Booth JCL, O´Grady J, Neuberger. Clinical Guidelines on the Management of Hepatitis C. 2001. British Society of Gastroenterology. Available from http://www.bsg.org.uk/clinical_prac/guidelines/hep_c.htm (accessed 24 Dec 2003).
2. Canadian Association for the Study of the Liver (CASL). Therapy for Chronic Hepatitis C. Available from : http://www.lhsc.on.ca/casl/hcther.htm (accessed 24 Dec 2003).
3. Centers for Disease Control and Prevention. Sexually Transmitted Diseases Treatment Guidelines 2002. MMWR 2002;51(RR-6):64-6. Available from: http://www.cdc.gov/mmwr//PDF/rr/rr5106.pdf (accessed 24 Dec 2003).
4. Clinical Effectiveness Group (Association of Genitourinary medicine and the Medical Society for the Study of Venereal Diseases). National Guideline on the Management of the Viral Hepatitides A, B & C. Available from: www.bashh.org (accessed 28 Nov 2003).
5. Cooksley WGE, Piratvisuth T, Lee S-D, Mahachai V, Chao YC, Tanwandee T, et al. Peginterferon alfa-2a (40kDa): an advance in the treatment of hepatitis B e antigen-positive chronic hepatitis B. J Viral Hepat 2003;10:298-305.
6. Cramp M, Rosenberg W. Guidance on the Treatment of Hepatitis C incorporating the Use of Pegylated Interferons. 2003. British Society of Gastroenterology. Available from: http://www.bsg.org.uk/clinical_prac/guidelines/pegylated.htm (accessed 24 Dec 2003).
7. Fried MW, Shiffman ML, Reddy R, Smith C, Marinos G, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002;347:975-82.
8. Health Canada – Sante Canada. Hepatitis C. Internet address: www.hc-sc.gc.ca/hppb/hepatitis_c/pdf/hepcMidterm/i_problem.html (accessed 17 Dec 2003).
9. Heathcote EJ, Shiffman ML, Cooksley GE, Dusheiko GM, Lee SS, Balart L, et al. Peginterferon alfa-2a in patients with chronic hepatitis C and cirrhosis. N Engl J Med 2000;343(23):1673-80.
10. Hugle T, Cerny A. Current therapy and new molecular approaches to antiviral treatment and prevention of hepatitis C. Rev Med Virol 2003;13:361-71.
11. Kamal SM, Fehr J, Roesler B, Peters T, Rasenack JW. Peginterferon alone or with ribavirin enhances HCV-specific CD4+ T-helper 1 response in patients with chronic hepatitis C. Gastroenterology 2002;123:1070-83.
12. Lamb, MW, Martin NE. Weight-based versus fixed dosing of peginterferon (40kDA) alfa-2a. Ann Pharmacother 2002;36:933-5.
13. Lauer GM, Walker BD. Hepatitis C virus infection. N Engl J Med 2001;345(1):41-52.
14. Lee SS, Heathcote J, Reddy KR, Zeuzem, Fried MW, Wright TL, et al. Prognostic factors and early predictability of sustained viral response with peginterferon alfa-2a (40KD). J Hepatol 2002;37(4):500-6.
15. National Institute for Clinical Excellence. Final Appraisal Determination – Interferon alfa (pegylated and non-pegylated) and ribavirin for the treatment of chronic hepatitis C. Available from: http://consensus.nih.gov/cons/116/hepatitis_c_consensus.pdf (Accessed 28 Nov 2003).
17. Patel K, McHutchinson JG. Current therapies for chronic hepatitis C: Drug" href="http://www.nice.org.uk/page.aspx?o=96374">http://www.nice.org.uk/page.aspx?o=96374
16. National Institutes of Health. NIH Concensus Statement on Management of Hepatitis C: 2002 19(3):1-52. Available from: http://consensus.nih.gov/cons/116/hepatitis_c_consensus.pdf (Accessed 28 Nov 2003).
17. Patel K, McHutchinson JG. Current therapies for chronic hepatitis C: Drug combination acheives sustained response in more than half of patients. Postgrad Med 2002;114(1):48-52,57-9,62.
18. Peltekian KM. Viral Hepatitis. Chapter 44. IN: Gray J, ed. Therapeutic Choices. Canadian Pharmacists Association. Ottawa, On. 2004. P.470-84.
19. Perry CM, Jarvis B. Peginterferon-alfa-2a (40kD): A review of its use in the management of chronic hepatitis C. Drugs 2001;61(15):2263-88.
20. Rasenack J, Zeuzem S, Feinman V, et al. Peginterferon alfa-2a (40D) [Pegasys ] improves HR-QOL outcomes compared with unmodified interferon alfa-2a [Roferon - A]. Pharmacoeconomics 2003;21(5):341-9.
21. Reddy KR, Modi MW, Peder S. Use of peginterferon alfa-2a (40 KD) (Pegasys ) for the treatment of hepatitis C. Adv Drug Deliv Rev 2002;54:571-86.
22. Reddy KR, Wright TL, Pockros PJ, Shiffman M, Everson G, Reindollar R, et al. Efficacy and safety of pegylated (40-kd) interferon alfa-2a compared with interferon alfa-2a in noncirrhotic patients with chronic hepatitis C. Hepatology 2001;33:433-8.
23. Sarrazin C, Hendricks DA, Sedarati F, Zeuzem S. Assessment, by transcription-mediated amplification, of virologic response in patients with chronic hepatitis C virus. J Clin Microbiol 2001;39(8):2850-5.
24. Yoho RA, Cruz LL, Mazaheri R, Cruz AT. Hepatitis C: A review. Plastic Reconstruct Surg 2003;112(2):597-605.
25. Zaman A, Fennerty MB, Keeffe EB. Systematic review: peginterferon vs. standard interferon in the treatment of chronic hepatitis C. Aliment Pharmacol Ther 2003;18:661-70.
26. Zeuzem S, Feinman SV, Rasenack J, Heathcote EJ, Lai MY, Gane E, et al. Peginterferon alfa-2a in patients with chronic hepatitis C. N Engl J Med 2000;343(23):1666-72.
27. Davis G. et al. Interferon Alfa-2b alone or in combination with ribavirin for the treatment of relapse of chronic hepatitis C. NEJM, 339;21:1493-1499, 1998.
28. Poynard T. et al. Randomised trial of interferon alpha-2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alpha-2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. Lancet, 352;9138:1426-1432, 1998.
29. McHutchison J. et al. Interferon Alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. NEJM, 339;21:1485-1492, 1998.
30. Poynard T. at al. Randomised trial of interferon alpha-2b plus ribavirin for 48 weeks versus interferon alpha-2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. Lancet, 352;9138:1431, 1998.
31. Battaglia AM, Hagmeyer KO. Combination therapy with interferon and ribavirin in the treatment of chronic hepatitis C infection. Ann Pharmacother 2000;34:487-94.
32. Glue P, Fang JWS, Rouzier-Panis R, et al. Pegylated interferon-alpha 2b: pharmacokinetics, pharmacodynamics, safety and preliminary efficacy data. Clin Pharmacol Ther 2000;68(5):556-67.
33. Glue P, Rouzier-Panis R, Raffanel C, et al. A dose-ranging study of pegylated interferon alfa-2b and ribavirin in chronic hepatitis C. Hepatology 2000;32(3):647-53.
34. Heathcote EJ, Shiffman ML, Cooksley WGE, et al. Peg interferon alfa-2a in patients with chronic hepatitis c and cirrhosis. N Engl J Med 2000;343:1673-80.
35. Liang TJ. Pathogenesis, natural history, treatment and prevention of hepatitis C. NIH Conference. Ann Intern Med 2000;132:296-305.
36. Freid MW, Shiffman ML, et al. Peginterferon Alfa-2a plus Ribavirin for Chronic Hepatitis C Virus Infection. NEJM 2002;347(13):975-982.
37. Manns MP, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomized trial.
Lancet 2001 Sep 22;358(9286):958-65.
38. The US Veterans Affairs National Hepatitis C Program guidelines. (Accessed November 21, 2001) www.va.gov/hepatitisc/pved/treatmntgdlnes_00.htm
39. Agency for Healthcare Research and Quality (AHRQ). Evidence Report/Technology Assessment No. 60, Management of Chronic Hepatitis C. Available at: www.ahrq.gov
40. Lindsay KL, et al. A randomized, double-blind trial comparing pegylated interferon alfa-2b to interferon alfa-2b as initial treatment for chronic hepatitis C.Hepatology 2001 Aug;34(2):395-403.
41. Canadian Liver Foundation National Hepatitis C Education Program. Hepatitis C: Medical Information Update. Can J Pub Health 2000;91(1):S4-9.
42. Gully PR, Tepper ML. Hepatitis C . CMAJ 1997;156:1427-8.
43. Alter MJ et al. The prevalence of Hepatitis C virus infection in the United States, 1988 through 1994. N Eng J Med 1999;339(21):1493-1499.
44. Zou S et al. Current status of Hepatitis C in Canada. Can J Pub Health 2000;91(1):S10-5.
45. Davis GL et al. Interferon alfa-2b alone or in combination with ribavirin for the treatment of relapse of chronic Hepatitis C. NEJM 1998;339(21):1493-9.
46. Scully et al. Clinical and epidemiologic characteristics of Hepatitis C in a gastroenterology/hepatology practice in Ottawa. Can Med Assoc J 1993;148:1173-7.
47. DiBiscegliee AM. Hepatitis C. Lancet 1998;3351:351-5.
48. Brady WM. Controversies in diagnosis and treatment of Hepatitis C. which patients benefit most from therapy? Postgrad Med 1997;102(5):201-12.
49. Canadian Association for Study of the Liver Consensus Conference Rapporteur Group. Canadian Consensus Conference on the management of viral Hepatitis. Can J Gast 2000;14 (Suppl B):5b-20b.
50. Mink et al. The prevalence of intrinsic host risk factors associated with progressive disease in patients with chronic Hepatitis C viral infections. Can J Pub Health 2000;91(3):171-5.
51. Sherlock S, Dusheiko G. Hepatitis C virus updated. Gut 1991;32:965-7.
52. Zou S et al. Prediction of Hepatitis C burden in Canada, Can J Gast 2000:14(7):575-80.
53. Yoshida EM et al. Indications for liver transplantation in British Columbia´s aboriginal population: a 10 year prospective analysis: Can J Gastro 2000;14(7):775-9.
54. National Institute of Health Consensus development conference statement: Management of Hepatitis C: 2002 June 10-12, 2002:1-44.
55. Futuh et al. Virologic response in patients with chronic Hepatitis C after treatment with interferon 2b alone or in combination with ribavirin(Abstract). 53rd Ann Mtg Am Assoc Study Liver Dis. Boston, MA, USA, Nov 1-5, 2002.
56. Futuh et al. Virologic response in patients with chronic Hepatitis C after treatment with interferon 2b alone or in combination with ribavirin(Abstract).
57. Consensus conference treatment of hepatitis C. February 27, 28, 2002, France.
58. The US Veterans Affairs National Hepatitis C Program guidelines. (Accessed November 21, 2001) www.va.gov/hepatitisc/pved/treatmntgdlnes_00.htm
59. Agency for Healthcare Research and Quality (AHRQ). Evidence Report/Technology Assessment No. 60, Management of Chronic Hepatitis C. Available at: www.ahrq.gov
60. AM, Hagmeyer KO. Combination therapy with interferon and ribavirin in the treatment of chronic hepatitis C infection. Ann Pharmacother 2000;34:487-94.