Report on New Patented Drugs - Agenerase
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 Excessive Price Guidelines (Guidelines), for all new active substances introduced after January 1, 2002.
Brand Name: Agenerase
Generic Name: (amprenavir)
DIN 02243541 50 mg capsule DIN 02243542 150 mg capsule DIN 02243543 15 mg/mL oral solution
Patentee: GlaxoSmithKline Inc.
Indication - as per product monograph:
For the treatment of protease inhibitor experienced, HIV-1 infected patients, in combination with other antiretroviral agents. In protease-inhibitor naïve patients, amprenavir is less effective than indinavir. In heavily pretreated protease-inhibitor experienced patients, amprenavir has not been sufficiently studied.
Notice of Compliance: March 1, 2001
Date of First Sale: March 16, 2001
Date of Issuance of First Patent(s) Pertaining to the Medicine: January 7, 2003
ATC Class: J05AE05 Antivirals for systemic use, Direct acting antivirals, Protease inhibitors.
Application of the Guidelines
The introductory prices of Agenerase at the date of first sale 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 prices did not exceed the range of prices in other comparator countries where Agenerase is sold or did not do so by an amount sufficient to trigger any of the investigation criteria under the Compliance and Enforcement Policy.
Agenerase is a new active substance and the PMPRB's Human Drug Advisory Panel (HDAP) recommended that Agenerase 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 recommended protease inhibitors Crixivan (indivavir), Fortovase (saquinavir), Viracept (nelfinavir) and Kaletra (lopinavir/ritonavir) as the most appropriate comparators to Agenerase 150 mg capsule and Kaletra for Agenerase 15 mg/mL. These agents share the same 4th level ATC classification and indication as Agenerase. The HDAP recommended ritonavir boosting for Agenerase and the protease inhibitor comparators, Crixivan (indivavir) and Fortovase (saquinavir). This is consistent with the Guidelines of the U.S. Department of Health and Human Services. The HDAP did not identify any comparators for Agenerase 50 mg capsule and recommended that it would be appropriate to compare it to Agenerase 150 mg capsule on a milligram-to-milligram basis.
The Guidelines provide that the dosage recommended for comparison purposes will normally not be higher than the maximum of the usual recommended dosage. The recommended comparable dosage regimens for Agenerase and the comparators are based on their respective product monographs and supported by clinical literature.
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. As shown in the table below, the prices of Agenerase (150 mg capsules and 15 mg/mL) were within the Guidelines in the introductory period (March 16 to June 30, 2001) as the cost of therapy did not exceed the cost of therapy with the comparator medicines or did not do so by an amount which would trigger the investigation criteria.
||Cot per Treatment
Agenerase (amprenavir) + Norvir SEC
|(ritonavir) 150 mg capsule + 100 mg capsule
||Amprenavir 1200mg + ritonavir 200mg (8 capsules + 2 capsules)
$1.92001 + $1.33542 _______ $3.2437
|$15.3600 + $2.6708 ________ $17.9372
||133.3 mg/ 33.3 mg capsule
||Lopinavir 800 mg/ritonavir 200 mg (6 capsules)
|Crixivan (indinavir) + Norvir SEC (ritonavir)
||400 mg capsule + 100 mg capsule
||Indinavir 1600 mg + ritonavir 200mg (4 capsules + 2 capsules)
||$2.69332 + $1.33542 _______ $4.0287
||$10.7732 + $2.6708 _______ $13.4440
|Fortovase (saquinavir) + Norvir SEC (ritonavir)
||200 mg capsule + 100 mg capsule
||Saquinavir 2000 mg + ritonavir 200 mg (10 capsules + 2 capsules)
||$1.02002 + $1.33542 _______ $2.3554
||$10.2000 + $2.6708 _______ $12.8708
||250 mg tablet
||Nelfinavir 2500 mg 10 tablets
|Agenerase (amprenavir) + Norvir SEC (ritonavir)
||15 mg/mL oral solution + 100 mg capsule
Amprenavir 91 mL + ritonavir 200 mg (91 mL oral solution + 2 capsules)
|$0.19201 + $1.33542 _______ $1.5274
||$17.4720 + $2.6708 _______ $20.1428
|Kaletra Liquid (lopinavir/ritonavir)
||80 mg/mL and 20 mg/mL oral solution
||Lopinavir 80 mg/mL/ ritonavir 20 mg/mL (10 mL oral solution)
1 Publicly available price as per the Patented Medicines Regulations 2 Liste de médicaments, Régie de l'assurance maladie du Québec, Avril 2001 3 Liste de médicaments, Régie de l'assurance maladie du Québec, Octobre 2001
As no comparators were identified for the 50 mg capsule, the price of the 50 mg capsule was compared to the price of the 150 mg capsule in a Reasonable Relationship test. Its price was within the Guidelines at introduction.
At the date of first sale, all three strengths of Agenerase were also being sold in France, Germany, Italy, Switzerland, United Kingdom and the United States. In compliance with the Guidelines, the price in Canada did not exceed the range of prices in those countries; the price of Agenerase in Canada was the third highest, above the median for the 50 mg capsule, second highest, above the median for the 150 mg capsule and third highest above the median, for the 15 mg/mL solution.
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.
- Arvieux C, Tattevin P, Souala FM et al. Salvage therapy with amprenavir and ritonavir: prospective study in 17 heavily pretreated patients. HIV Clinical Trials 2002;3(2):125-32.
- British HIV Association (BHIVA) guidelines for the treatment of HIV-infected adults with antiretroviral therapy. BHIVA Writing Committee on behalf of the BHIVA Executive Committee, July 2003. http://www.bhiva.org/guidelines/2003/hiv/index.html
- Department of Health and Human Services (DHHS). Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, updated November 2003. http://aidsinfo.nih.gov/guidelines/default_db2.asp?id=50
- Department of Health and Human Services (DHHS). Panel on Clinical Practices for the Treatment of HIV Infection. Guidelines for the use of antiretroviral agents in the HIV-1 infected adults and adolescents. March 23, 2004. Available at: http://AIDSinfo.nih.gov.
- Eron JJ, Haubrich R, Lang W et al. A phase II trial of dual protease inhibitor therapy: amprenavir in combination with indinavir, nelfinavir, or saquinavir. JAIDS 2001;26(5):458-61.
- Falloon J, Piscitelli S, Vogel S et al. Combination therapy with amprenavir, abacavir, and efavirenz in human immunodeficiency virus (HIV) infected patients failing a protease-inhibitor regimen: pharmacokinetic drug interactions and antiviral activity. Clin Infec Dis 2000;30(2):313-8.
- Goodgame JC, Pottage JC, Jablonowski H et al. Amprenavir in combination with lamivudine and zidovudine versus lamivudine and zidovusine alone in HIV-1 infected antiretroviral naïve patients. Amprenavir PROAB3001 International Study Team. Antiviral Therapy 2000;5(3):215-25.
- Hammer SM, Vaida F, Bennett KK et al. Dual vs single protease inhibitor therapy following antiretroviral treatment failure: a randomized trial. JAMA 2002;288(2):169-80.
- Haubrich R, Thompson M, Schooley R et al. A phase II safety and efficacy study of amprenavir in combination with zidovudine and lamivudine in HIV-infected patients with limited antiretroviral experience. Amprenavir PROAB2002 Study Team. AIDS 1999;13(7):2411-20.
- Kost RG, Hurley A, Zhang L et al. Open-label phase II trial of amprenavir, abacavir, and fixed-dose zidovudine/lamivudine in newly and chronically HIV-1 infected patients. JAIDS 2001;26(4):332-9.
- Murphy RL, Gulick RM, DeGruttola V et al. Treatment with amprenavir alone or amprenavir with zidovudine and lamivudine in adults with human immunodeficiency virus infection. AIDS Clinical Trials Group 347 Study Team. J Infec Dis 1999;179(4):808-16.
- Noble S, Goa KL. Amprenavir; A review of its clinical potential in patients with HIV infection. Drugs 2000;60(6):1383-1410.
- Pediatric Dosage Handbook 2001-2002, 8th edition. Taketomo CK, Hodding JH, Kraus DM (eds). Lexi-Comp Inc., Hudson, OH, 2001.
- Schooley RT, Clumeck N, Haubrich R et al. A dose-ranging study to evaluate the antiretroviral activity and safety of amprenavir alone and in combination with abacavir in HIV-infected adults with limited antiretroviral experience. Antiviral Therapy 2001;6(2):89-96. (medline abstract only)
- The Sanford Guide to HIV/AIDS Therapy 2002, 11th edition. Sande MA, Gilbert DN, Moellering RC (eds). Antimicrobial Therapy Inc., Hyde Park, VT, 2002.
- Yeni et al. Treatment for adult HIV infection: 2004 recommendations of the International AIDS Society-USA panel. JAMA 2004;292:251-265.