Tenofovir disoproxil fumarate with emtricitabine, tablet, 300 mg -200 mg, Truvada®, November 2005
Public Summary Document for tenofovir disoproxil fumarate with emtricitabine, tablet, 300 mg -200 mg, Truvada®, November 2005
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Public Summary Document
Product: Tenofovir disoproxil fumarate with emtricitabine, tablet, 300 mg -200 mg, Truvada®
Sponsor: Gilead Sciences Australia Pty Ltd
Date of PBAC Consideration: November 2005
1. Purpose of Application
The application sought listing on the PBS as a Section 100 item (Highly Specialised
Drug) for the treatment of Human Immunodeficiency Virus (HIV) infection.
2. Background
This was the first application seeking listing of this combination product on the
PBS.
3. Registration Status
Truvada is TGA-registered for the treatment of HIV infected adults over the age of
18 years, in combination with other antiretroviral agents. This indication is based
on analyses of plasma HIV-1 RNA levels and CD4 cell counts in controlled studies of
VIREAD® and EMTRIVA® in treatment-naive and treatment experienced adults.
4. Listing Requested and PBAC’s View
Section 100
Private hospital authority required
Treatment of HIV infection in patients with:
(a) CD4 cell counts of less than 500 per cubic millimetre; or
(b) viral load of greater than 10,000 copies per mL.
The PBAC noted that the requested listing was identical to the listings for the individual
components.
5. Clinical Place for the Proposed Therapy
Combination therapy, comprising of at least three antiretroviral (ARV) agents, is
standard care in the management of HIV infection. As part of this therapy, dual Nucleotide
Reverse Transcriptase Inhibitor (NRTI) use is widely recommended. The combination
product would replace use of the two drugs administered as separate products, reducing
the pill burden and assisting in maintaining adherence to a treatment regime.
6. Comparator
The submission nominated concomitant tenofovir disoproxil fumarate and emtricitabine
as the comparator. This was considered appropriate by the PBAC.
7. Clinical Trials
The basis of the submission was 1) one randomised open-label cross-over trial evaluating
the pharmacokinetic interactions between tenofovir disoproxil fumarate and emtricitabine
at steady state, and 2) one randomised, cross-over trial evaluating the bioequivalence
of tenofovir disoproxil fumarate with emtricitabine fixed dose combination versus
concomitant tenofovir & emtricitabine. Both of these trials were in healthy volunteers.
A supporting randomised trial was also included comparing tenofovir disoproxil fumarate
with emtricitabine and efavirenz with Combivir® (lamivudine with zidovudine) and efavirenz
in treatment naïve HIV-1 infected patients.
8. Results of Trials
The PBAC noted the pharmacokinetic parameters were comparable when either tenofovir
disoproxil fumarate or emtricitabine were given alone or in combination. The pharmacokinetic
parameters of tenofovir disoproxil fumarate and emtricitabine were also similar whether
given in a fixed dose combination or concomitantly.
In the supporting trial, concomitant tenofovir disoproxil fumarate and emtricitabine
(and efavirenz) resulted in 81% of patients in the Intention to Treat (ITT) population
being classified as responders at 48 weeks of treatment. Virological failure occurred
in only 7/255 (2.7%) of tenofovir disoproxil fumarate with emtricitabine (and efavirenz)
treated patients.
The PBAC noted that similar levels of adverse events occurred in normal subjects dosed
with the fixed dose combination tablet compared to concomitant tenofovir disoproxil
fumarate and emtricitabine. In antiretroviral treatment naïve HIV-1 infected patients
at 48 weeks of tenofovir disoproxil fumarate with emtricitabine (and efavirenz) treatment
the most common adverse events were dizziness, nausea, diarrhoea, abnormal dreams,
fatigue, headache and insomnia. A total of 37/257 (14%) of patients reported treatment-emergent
adverse events.
9. Clinical Claim
The submission described tenofovir disoproxil fumarate with emtricitabine fixed dose
combination tablet as having similar effectiveness and toxicity compared to concomitant
tenofovir disoproxil fumarate and emtricitabine. The claim was accepted by the PBAC.
10. Economic Analysis
The submission presented a preliminary economic evaluation. The choice of the cost-minimisation
approach was considered valid. The resources included were drug costs. The overall
comparative costs for each alternative (the fixed dose combination of tenofovir disoproxil
fumarate with emtricitabine and concomitant tenofovir disoproxil fumarate and emtricitabine)
were the same. In the context of cost-minimisation the equi-effective doses were tenofovir
disoproxil fumarate 300mg with emtricitabine 200mg fixed dose combination tablet and
concomitant tenofovir disoproxil fumarate 300mg and emtricitabine 200mg.
11. Estimated PBS Usage and Financial Implications
The submission calculated that there would be no cost to the PBS since tenofovir disoproxil
fumarate with emtricitabine fixed dose combination tablet would only substitute for
concomitant tenofovir disoproxil fumarate and emtricitabine. However, the PBAC noted
the possibility that the fixed dose combination may replace other NRTI combinations
of a lower cost, and it was thus likely there would some additional cost to the PBS.
12. Recommendation and Reasons
Consistent with its policy on fixed dose combination products, the PBAC recommended
listing on a cost-minimisation compared to the corresponding strengths of the individual
components, as the data presented indicate that Truvada, as requested, has similar
safety and efficacy compared to concomitant tenofovir 300mg and emtricitabine 200mg
daily.
Recommendation
TENOFOVIR DISOPROXIL FUMARATE with EMTRICITABINE, tablet,
300 mg-200 mg
Details of the PBAC's Recommendation:
| Restriction: | Section 100 (Highly Specialised Drug) Private hospital authority required Treatment of HIV infection in patients with: (a) CD4 cell counts of less than 500 per cubic millimetre; or (b) viral load of greater than 10,000 copies per mL. |
| Pack Size: | 30 |
13. Context for Decision
The PBAC helps decide whether and, if so, how medicines should be subsidised in Australia.
It considers submissions in this context. A PBAC decision not to recommend listing
or not to recommend changing a listing does not represent a final PBAC view about
the merits of the medicine. A company can resubmit to the PBAC or seek independent
review of the PBAC decision.
14. Sponsor’s Comment
No Comment
