Report on New Patented Drugs - Viread

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: Viread

Generic Name: tenofovir disoproxil fumerate

DIN: 02247128 - Oral tablet

Patentee: Gilead Sciences, Inc.

Indication - as per product monograph: For the treatment of HIV-1 infection in combination with other antiretroviral agents in patients 18 years of age and older who have experienced virologic failure on other regimens.

Notice of Compliance: March 18, 2003

Date of First Sale: March 15, 2004

ATC Class: J05AF
Nucleoside and nucleotide reverse transcriptase inhibitors (NRTI).

APPLICATION OF THE GUIDELINES

Summary:

Pursuant to an Advance Ruling Certificate (ARC) issued June 3, 2004, the Board is satisfied on the basis of the information submitted and on the facts available at the time that there would not be sufficient grounds to make an order under section 83 of the Patent Act in respect of the price of Viread 300 mg tablet (DIN 02247128).

Background:

On April 13, 2004, the Board published a Notice and Comment proposing to issue an ARC with respect to the medicine Viread. Following negotiations, Gilead and Board Staff agreed that Gilead would propose to sell Viread in Canada at an average price not to exceed $15.1250 per 300 mg tablet.

Ministers of Health in the provinces and territories and other interested parties were invited to make submissions regarding the proposed ARC on or before May 7, 2004. Gilead and Board Staff were given the opportunity to submit written responses to any submissions no later than May 25, 2004.

The Board received one submission in response to the Notice from the Canadian Treatment Action Council (CTAC). There were no submissions from the Ministers of Health in the provinces and territories. Gilead and Board Staff filed written submissions in response to the submissions from CTAC.

Having considered the submissions of CTAC, Gilead and Board Staff, and based on the facts available at the time, the Chairperson concluded that there would not be sufficient grounds to make an order under section 83 of the Act and that it is in the public interest to issue the ARC with respect to the proposed price of Viread.

Scientific and Price Review:

Viread is a new active substance and the PMPRB's Human Drug Advisory Panel (HDAP) recommended that Viread be reviewed as a category 3 new medicine (provides moderate, little or no therapeutic advantage over comparable medicines) and that it be compared to all nucleoside reverse transcriptase inhibitors within the same 4th level of the Anatomical, Therapeutic, Chemical (ATC) System.

One of the tests under the PMPRB's Guidelines for determining whether the introductory price of a category 3 new drug product is excessive is whether it exceeds the prices of the comparable drug products in the same therapeutic class in a Therapeutic Class Comparison (TCC) test. See the PMPRB's Compendium of Guidelines, Policies and Procedures for a more complete description of the Guidelines and the policies on TCCs. The 4th level ATC comparators include Ziagen (abacavir), Retrovir (zidovudine), Videx (didanosine), Videx EC (didanosine), Hivid (zalcitabine), Zerit (stavudine) and 3TC (lamivudine). In conducting the TCC, the highest cost per day of therapy in the class was Ziagen at $12.50. The table from Attachment 2 of the Notice and Comment dated April 8, 2004 is reproduced here.

Viread Therapeutic Class Comparison

A second test under the Guidelines for purposes of reviewing the introductory price of a category 3 new drug product is whether the Canadian price exceeds the prices in the countries listed in the Patented Medicines Regulations. Viread is sold in all seven comparator countries. Prices in these countries range from $12.6759 (Italy) to $21.3184 (France). The median international price is $18.3751. The table from Attachment 3 of the Notice and Comment dated April 8, 004 is reproduced below.

Viread International Price Comparison (Can$)

Subsection 85(1)(c) of the Patent Act (“Act”) states that the Board shall take into consideration “the prices at which the medicine and other medicines in the same therapeutic class have been sold in countries other than Canada.” Among other things, Viread as the first and only nucleotide in the 4th level ATC class of nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs) is sold at a premium to the nucleosides in the class in all seven comparator countries. The proposed MNE price of $15.1250 per tablet is based on the median of the ratios of the prices of Viread to Ziagen, the pivotal comparator in a TCC test and the most recent entrant in the same 4th level ATC class, in those countries. The proposed Canadian price in 2004 is well below the median of the international prices; it will be the second lowest of the seven comparator countries

Pursuant to section 85 of the Act, and for purposes of determining whether the price of Viread is excessive under section 83, the Chairperson concluded based on the submissions of CTAC, Gilead and Board Staff and on the facts available at the time that there would not be sufficient grounds to make an order under section 83 of the Act and that it is in the public interest to issue an ARC with respect to the proposed price of $15.1250 per tablet for the medicine Viread.

The PMPRB will continue to monitor the price of Viread to ensure that it complies with the Board's Guidelines while it remains under the PMPRB's jurisdiction.

The Viread ARC is available on the PMPRB website under Publications, Advance Ruling Certificates.

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.

Evidence/References considered by the HDAP

Margot NA, Isaacson E, McGowan I, Cheng A, Miller MD. Extended treatment with tenofovir disoproxil fumarate in treatment-experienced HIV-1-infected patients: genotypic, phenotypic, and rebound analyses. J Acquir Immune Defic Syndr. 2003 May 1;33(1):15-21.

Staszewski S, Gallant JE et al. Efficacy and safety of tenofovir DF vs. stavudine when used in combination with lamivudine and efavirenz in antiretroviral naïve patients: 96-week preliminary results. (Poster) 10th Conference on Retroviruses and Opportunistic Infections Feb 10-14, 2003.

Squires K, Pozniak AL, et al. Tenofovir DF in antiretroviral-experienced nucleoside resistant HIV-1 infected patients with incomplete viral suppression. Manuscript.

Schooley RT, Ruane P, Myers RA, et al. Tenofovir DF in antiretroviral-experienced patients: results from a 48-week, randomized, double-blind study. AIDS 2002;16:1257-63.

Louie M, Hogan C, Hurley A, Simon V, Chung C, Padte N, Lamy P, Flaherty J, Coakley D, Di Mascio M, Perelson AS, Markowitz M. Determining the antiviral activity of tenofovir disoproxil fumarate in treatment-naive chronically HIV-1-infected individuals. AIDS 2003; 17(8):1151-1156.

Epi Updates: http://www.hc-sc.gc.ca/pphb-dgspsp/publicat/epiu-aepi/hiv-vih/pdf/epiact_0403_e.pdf

Division of HIV/AIDS Prevention : Basic Statistics. http://www.cdc.gov/hiv/stats.htm, accessed June 5, 2003.

Guidelines for Using Antiretroviral Agents Among HIV-Infected Adults and Adolescents: Recommendations of the Panel on Clinical Practices for Treatment of HIV. MMWR 2002;51(RR-7). http://www.cdc.gov/mmwr/PDF/rr/rr5107.pdf

Yeni PG, Hammer SM, Carpenter CCJ et al. Antiretroviral treatment for adult HIV infection in 2002: Updated Recommendations of the International AIDS Society-USA Panel. JAMA 2002;288(2):222-35.

Staszewski S, Gallant J, Pozniak A et al. Efficacy and safety of tenofovir disoproxil fumarate (TDF) versus stavudine (d4T) when used in combination with lamivudine (3TC) and efavirenz (EFV) in HIV-1 infected patients naïve to antiretroviral therapy (ART); 48 week interim results. 14th International AIDS conference, Barcelona, pain, July 7-12, 2002. Abstract No. Lb0r17. http://www.aegis.com/conferences/14wac/LBOr17.html, accessed June 25th, 2003.

Hosein S. From the XIV International AIDS Conference: Tenofovir looks good in initial therapy. Catie News, July 30, 2002. http://www.aegis.com/news/catie/2002/CATE-N20020705.html, accessed June 25th, 2003.

Squires K, Pierone G, Berger D, et al. Tenofovir DF: A 24-week interim analysis from a Phase III double blind, placebo, controlled study in antiretroviral experienced patients. 41st Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, Illinois, USA, December 16-19, 2001. Abstract I-666.

Margot NA, Zhong L, Wulfsohn M et al. Probability and durability of achieving <50 copies/mL of HIV RNA by treatment intensification with tenofovir DF. 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, CA, USA, September 27-30, 2002. Abstract H-1077.

Schooley RT, Ruane P, Myers RA, et al. Tenofovir DF in antiretroviral-experienced patients: results from a 48-week, randomized, double-blind study. AIDS 2002;16:1257-63.

Louie M, Hogan C, Di Mascio M, et al. Determining the relative efficacy of highly active antiretroviral therapy. JID 2003;187:896-900.

Deeks SG, Barditch-Crovo P, Lietman PS, et al. Safety, pharmacokinetics, and antiretroviral activity of intravenous 9-[2-®-(Phosphonomethoxy)propyl]adenine, a Novel anti-Human Immunodeficiency Virus (HIV) Therapy, in HIV-infected adults. Antimicrob. Agents Chemother. 1998;42(9):2380-4.

Barditch-Crovo P, Deeks SG, Collier A, et al. Phase I/II trial of the pharmacokinetics, safety, and antiretroviral activity of tenofovir disoproxil fumarate in Human Immunodeficiency Virus-Infected adults. Antimicrob. Agents Chemother. 2001;45(10):2733-9.

Grim SA, Romanelli F. Tenofovir disoproxil fumarate. Ann Pharmacother 2003;37:849-59.

The British HIV July 2003 guidelines: (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)

DHHS. Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection, updated June 25, 2003. (http://www.aidsinfo.nih.gov/guidelines/pediatric/PED_062503.pdf)

DHHS. Pediatric Guidelines Supplement, Pediatric Antiretroviral Drug Information, updated June 25, 2003. (http://aidsinfo.nih.gov/guidelines/default_db2.asp?id=51)