Report on New Patented Drugs – Celsentri
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: Celsentri
Generic Name: (maraviroc)
DIN: 02299844 (150 mg tablet)
02299852 (300 mg tablet)
Patentee: Pfizer Canada Inc.
Indication – as per product monograph:
In combination with other antiretroviral agents, is indicated for treatment-experienced adult patients infected with CCR5-tropic HIV-1 who have evidence of resistance to multiple antiretroviral agents.
Date of Issuance of First Patent(s) Pertaining to the Medicine:
June 27, 2006
Notice of Compliance: September 21, 2007
Date of First Sale: October 16, 2007
ATC Class: J05AX
Antiinfectives For Systemic Use; Antivirals For Systemic Use; Direct Acting Antivirals; Other antivirals
Application of the Guidelines
The introductory prices of Celsentri 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 did not exceed the range of prices of the same medicine in the comparator countries listed in the Patented Medicines Regulations (Regulations) where Celsentri was sold.
Celsentri is a new active substance and the PMPRB's Human Drug Advisory Panel (HDAP) recommended that Celsentri be classified 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 World Health Organization (WHO) Anatomical Therapeutic Chemical (ATC) classification 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.
The HDAP recommended Aptivus (tipranavir), Fuzeon (enfuvirtide), and Prezista (darunavir) as the most appropriate comparators to Celsentri. Fuzeon shares the same 4th level ATC class as Celsentri and is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in treatment-experienced patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy. Aptivus and Prezista, two protease inhibitors, which do not share the same 4th level ATC class as Celsentri, are both indicated for treatment-experienced patients infected with HIV. They are included in treatment guidelines and review documents as treatment options for treatment-experienced adult patients.
The Guidelines provide that the dosage recommended for comparison purposes will normally not be higher than the maximum of the usual recommended dosage. The comparative dosage regimens for Celsentri and the comparators are based on products monographs, guidelines and published clinical trials.
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 based on the TCC test, or if it exceeds the range of the prices of the same medicine in the seven comparator countries listed in the Regulations.
The introductory prices of Celsentri 150 mg and 300 mg tablets were within the Guidelines as the cost of treatment did not exceed the cost of treatment of the comparator medicines.
Introductory Period (October to December 2007)
|Brand Name (generic)
||Dosage Regimen (daily)
||Cost per Treatment (daily)
||150 mg / tablet
||300 mg / tablet
||108 mg / vial
|Aptivus (tipranavir) + Norvir Sec (ritonavir)
||250 mg / capsule + 100 mg / capsule
||4 capsules + 4 capsules
||$8.2500(2) + $1.3625(2)
||$33.0000(2) + $5.4500(2) $38.4500
|Aptivus (tipranavir) + Norvir Liquid (ritonavir)
||250 mg / capsule + 80 mg / mL
||4 capsules + 5 mL
||$8.2500(2) + $1.0898(2)
||$33.0000(2) + $5.4490(2) $38.4490
|Prezista (darunavir ethanolate) + Novir Sec (ritonavir)
||300 mg / tablet + 100 mg / capsule
||4 tablets + 2 capsules
||$6.9600(2) + $1.3625(2)
||$27.8400(2) + $2.7250(2) $30.5650
|Prezista (darunavir ethanolate) + Novir Liquid (ritonavir)
||300 mg / tablet + 80 mg / mL
||4 tablets + 2.5 mL
||$6.9600(2) + $1.0898(2)
||$27.8400(2) + $2.7245(2) $30.5645
(1) Publicly available prices as per Regulations
(2) Liste de médicaments du Québec, Régie de l'assurance de médicaments du Québec, Octobre, 2007
In 2007, Celsentri was being sold in four countries listed in the Regulations, namely France, Germany, Sweden and the United States. In compliance with the Guidelines, the prices of Celsentri in Canada did not exceed the range of prices in those countries. They were the lowest international prices.
The publication of Summary Reports is part of the PMPRB's commitment to make its price review process 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 product 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 – Celsentri
1. Aberg JA, Gallant JE, Anderson J, Oleske JM, Libman H, Currier JS, et al. Primary care guidelines for the management of persons infected with human immunodeficiency virus: recommendations of the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2004 Sep 1;39(5):609-29.
2. American Society of Health-System Pharmacists. AHFS Drug Information® (2007). In: STAT!Ref Online Electronic Medical Library. Bethesda: American Society of Health-System Pharmacists; 2007.
3. Anon. Drugs for HIV Infection. Treat Guidel Med Lett. 2006 Oct;4(50):67-76.
4. Aptivus Product Monograph. e-CPS 2007.
5. Bartlett JG. Modifying HIV antiretroviral therapy regimens. Up To Date Online, November 17, 2006. Accessed online at: www.utdol.com.
6. Boulos D, Yan P, Schanzer D, Remis RS, Archibald CP. Estimates of HIV prevalence and incidence in Canada, 2005. Can Commun Dis Rep. 2006 Aug 1;32(15):165-74. Available from: http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/06pdf/cdr3215.pdf
7. Canadian Pharmacists Association. e-CPS. Ottawa: Canadian Pharmacists Association; 2007.
8. Choe H, Farzan M, Sun Y, et al. The ß-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates. Cell 1996; 85: 1135-48.
9. ClinicalTrials.gov. Trial of Maraviroc (UK-427,857) in Combination With Zidovudine/Lamivudine Versus Efavirenz in Combination With Zidovudine/Lamivudine. Available: http://www.clinicaltrials.gov/ct/show/NCT00098293?order=4
10. de Roda Husman AM, Koot M, Cornelissen M et al. Association between CCR5 genotype and the clinical course og HOV-1 infection. Ann Inter Med 1998; 127L 882-90.
11. Deng H, Liu R, Ellmeier W et al. Identification of a major co-receptor for primary isolates of HIV-1. Nature 1996; 381: 661-6.
12. Department of Health and Human Services. Guidelines for the use of antiretroviral agents in HIV-1 infected adults and adolescents. October 10, 2006.
13. Dodds C, Colman R, Amaratunga C, Wilson J. The cost of HIV/AIDS in Canada. GPI Atlantic. http://pubs.cpha.ca/PDF/P30/22756.pdf.
14. Dragic T, Litwin V, Allaway GP et al. HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5. Nature 1996; 381: 667-73.
15. Feng Y, Broder CC, Kennedy PE et al. HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G-protein-coupled receptor. Science 1996; 272: 872-7.
16. Fuzeon Product Monograph. e-CPS 2007.
17. Gazzard B, Bernard AJ, Boffito M, Churchill D, Edwards S, Fisher N, et al; Writing Committee, British HIV Association. British HIV Association (BHIVA) guidelines for the treatment of HIV-infected adults with antiretroviral therapy (2006). HIV Med. 2006 Nov;7(8):487-503. Available: http://www.bhiva.org/files/file1001303.pdf
18. Hammer SM, Saag MS, Schechter M, Montaner JS, Schooley RT, Jacobsen DM, et al. Treatment for adult HIV infection: 2006 recommendations of the International AIDS Society-USA panel. JAMA. 2006 Aug 16;296(7):827-43.
19. Health Canada. Drug Product Search. Available from: http://cpe0013211b4c6dcm0014e88ee7a4.cpe.net.cable.rogers.com/dpdonline/startup.do?applanguage=en_CA
20. Imunovir Product Monograph. e-CPS 2007.
21. Jones J, Taylor B, Wilkin TJ, Hammer SM. Advances in antiretroviral therapy. Top HIV Med. 2007 Apr-May;15(2):48-82.
22. Lalezari JP, Henry K, O<Hearn M et al. Enfuvirtide, and HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America. NEJM 2003; 348: 2175-85.
23. Liu R, Paxton WA, Choe A, et al. Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell 1996; 86: 367-77.
24. Marmor M, Shepherd HW, Donnell D et al. Homozygous and heterozygous CCR5-Delta32 genotypes are associated with resistance to HIV infection. J Acq Imm Def Synd 2001; 27: 472-81.
25. Marschner IC, Collier AC, Coombs RW, et al. Use of changes in plasma levels of human immunodeficiency virus type 1 RNA to assess the clinical benefit of antiretroviral therapy. J Infect Dis 1998; 177(1): 40-7.
26. Napravnik S, Edwards D, Stewart P, et al. HIV-1 drug resistance evolution among patients on potent combination antiretroviral therapy with detectable viramia. J Acq Imm Def Syndr 2005; 40: 34-40.
27. National Horizon Scanning Centre. New and Emerging Technology Briefing. Maraviroc (UK 427857) for resistant HIV. August 2006. Available at: http://pcpoh.bham.ac.uk/publichealth/horizon/PDF_files/2006reports/Maraviroc.pdf
28. Panel on Antiretroviral Guidelines for Adult and Adolescents. Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. Department of Health and Human Services. October 10, 2006. Available: http://aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL.pdf
29. Piacenti FJ. An update and review of antiretroviral therapy. Pharmacotherapy. 2006 Aug;26(8):1111-33.
30. Powderly WG, Saag MS, Chapman S, et al. Predictors of optimal virologic response to potent antiretroviral therapy. AIDS 1999; 13(14): 1873-80.
31. Prezista Product Monograph. e-CPS 2007.
32. Richman DD, Morton SC, Wrin T, et al. The prevalence of antiretroviral drug resistance in the United States. AIDS 2004; 18(10): 1393-401.
33. Samson M, Libert F, Doranz BJ et al. Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature 1996; 382: 722-5.
34. Sax PE. Therapeutic options for treatment experienced patients: a focus on resistance testing and optimizing background therapy. AIDS Read. 2006 May;16(5):265-75, 277-8.
35. Stephenson J. Researchers buoyed by novel HIV drugs: will expand drug arsenal against resistant virus. JAMA. 2007 Apr 11;297(14):1535-6.
36. Sterne JA, Hernan MA, Ledergerber B, et al. Long-term effectiveness of potent antiretroviral therapy in preventing AIDS abd death: a prospective cohort study. Lancet 2005; 366(9483): 378-84.
37. Temesgen Z, Cainelli F, Poeschla EM, Vlahakis SA, Vento S. Approach to salvage antiretroviral therapy in heavily antiretroviral-experienced HIV-positive adults. Lancet Infect Dis. 2006 Aug;6(8):496-507.
38. TheBody.com. Isoprinosine Info Sheet. May 1996. Available: http://www.thebody.com/content/art4749.html
39. Tsibris AM, Kuritzkes DR. Chemokine antagonists as therapeutics: focus on HIV-1. Annu Rev Med. 2007;58:445-59.
40. Walli R, Reinhart B, Lickow B, et al. HIV-1 infected long-term slow progressors hetegozygous for ?32-CCR5 show significantly lower plasma viral load than wild-type slow progressors. J Acquir Immune Defic Syndr Hum Retrovirol 1998; 18(3): 229-33.
41. WHO Collaborating Centre for Drug Statistics Methodology [database on the Internet; cited June 27, 2007]. Available: http://www.whocc.no/atcddd/
42. Yamashita TE, Phair JP, Munoz A, et al. Immunologic and virologic response to highly active antiretroviral therapy in the Multicenter AIDS Cohort Study. AIDS 2001; 15(6): 735-46.