Abacavir Sulfate with Lamivudine, tablet, 600 mg (base) - 300 mg, Kivexa®, July 2005

Public Summary Document for Abacavir Sulfate with Lamivudine, tablet, 600 mg (base) - 300 mg, Kivexa®, July 2005.

Page last updated: 24 October 2005

Public Summary Document
Product: Abacavir Sulfate with Lamivudine, tablet, 600 mg (base) - 300 mg, Kivexa®,
Sponsor: GlaxoSmithKline Australia
Date of PBAC Consideration: July 2005

1. Purpose of Application

This application sought listing on the Pharmaceutical Benefits Scheme (PBS) as a Section 100 item (Highly Specialised Drug) for the treatment of Human Immunodeficiency Virus (HIV). (Highly Specialised Drugs (HSDs) are medicines for the treatment of chronic conditions, which, because of their clinical use or other special features, are restricted to prescribing through public and private hospitals which have appropriate specialist facilities.)

2. Background

This product had not previously been considered by the Pharmaceutical Benefits Advisory Committee (PBAC).

3. Registration Status

Kivexa tablets were approved by the Therapeutic Goods Administration on 7 March 2005 for use "in antiretroviral combination therapy for the treatment of HIV infection in adults and adolescents from 12 years of age".

4. Listing Requested and PBAC’s View

The sponsor requested the following listing:

Section 100
Private hospital authority required
Treatment, in combination with other antiretroviral agents, of HIV infection in patients over 12 years of age, 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 sponsor had agreed the listing be modified to (a) restrict treatment to patients weighing 40 kg or more in accordance with the Australian approved product information and because this is a fixed dose product, and (b) to remove the reference to combination with other antiretroviral agents for consistency with the restrictions of similar PBS-listed products.

5. Clinical Place for the Proposed Therapy

Abacavir and lamivudine are Nucleoside Reverse Transcriptase Inhibitors (NRTIs) and are potent, selective inhibitors of HIV-1 and HIV-2. Combination therapy, comprising of at least three antiretroviral agents, is standard care in the management of HIV infection. As part of this therapy, dual NRTI use is widely recommended.

6. Comparator

The submission nominated abacavir co-administered with lamivudine, both as single agents as the comparator. This was considered appropriate by PBAC.

7. Clinical Trials

The submission presented the results of one key clinical trial, CAL30001 and two supportive trials, ESS30008 and CNA30021.

All studies had been published at the time of submission, as follows:

Trial/first author	Protocol title	Publication citation
CAL30001/ 1. Clumeck N 2. Craig C	A Phase III, randomized, open-label, parallel, multicenter study to evaluate treatment with fixed-dose combination of abacavir/lamivudine (600mg/300mg) once-daily versus abacavir (300mg) twice-daily and lamivudine (300mg) once-daily in combination with tenofovir once-daily and a new PI or NNRTI for 48 weeks in ART-experienced HIV-1 infected patients.	1. 44th ICAAC Washington Oct 30-Nov 2 2004 Poster H-558. 2. 7th International Congress on Drug Therapy in HIV infection. Glasgow 14-18 Nov 2004. Poster 314.
ESS30008/ 1. Watson M 2. Sosa N	A Phase III, 48-week, open-label, randomized, multicenter study of the safety and efficacy of the abacavir/lamivudine fixed dose combination tablet administered QD versus abacavir + lamivudine administered BID in combination with a PI or NNRTI in antiretroviral experienced patients.	1. 7th International Congress on Drug Therapy in HIV infection. Glasgow 14-18 Nov 2004. Poster P44 2. Ibid Poster P45.
CNA30021/ 1. Gazzard B 2. Craig C 3. Hernandez J 4. Gordon D	A Phase III, 48-week, randomized, double-blind multicenter study to evaluate the safety and efficacy of the abacavir 600mg once daily vs abacavir 300mg BID in combination with lamivudine (300mg once daily) and efavirenz (600mg once daily) in antiretroviral therapy naïve HIV-1 infected subjects.	1. 43rd ICAAC Chicago 14-17 Sept 2003. Abs H-1722b 2. 11th Conference on Retroviruses and Opportunistic Infections San Francisco Feb 8-11 2004. Poster 551. 3. XV IAC Bangkok July 11-16 2004 Poster TuPeB 4521. 4. ibid Poster WePeB 5868.

Trial CNA30021 was not considered by PBAC on the grounds that it did not evaluate the efficacy or safety of the fixed combination tablet.

8. Results of Trials

In the two clinical trials, CAL30001 and ESS 30008, the fixed combination of abacavir 600 mg with lamivudine 300 mg was no worse than concomitant administration of the single agents in any of the primary or secondary outcomes measured.

The toxicity profile for abacavir with lamivudine fixed dose combination tablet was consistent with the experience from the use of the individual components.

9. Clinical Claim

The PBAC accepted the submission’s claim that the fixed combination product is no worse than concomitant abacavir 600 mg and lamivudine 300 mg in terms of efficacy and toxicity.

10. Economic Analysis

A cost minimisation analysis was presented based on monthly treatments cost (ex-manufacturer) of the single agents. This approach was considered acceptable by PBAC.

11. Estimated PBS Usage and Financial Implications

The submission claimed that listing of the fixed dose combination would not have any net financial cost for the PBS, as the majority of usage would replace the combination use of the individual components. The submission further claimed that as it could also replace some more expensive NRTIs, the listing of Kivexa could result in some savings to the PBS.

12. Recommendation and Reasons

Consistent with its policy on fixed dose combination products, the PBAC recommended listing on a cost-minimisation basis compared to the corresponding strengths of the individual components as the data from the two prospectively designed non-inferiority trials indicate once daily Kivexa as requested has similar safety and efficacy compared to concomitant abacavir 600 mg and lamivudine 300 mg daily.

Recommendation
List
Section 100 (Highly Specialised Drugs):

 

Restriction:	Private hospital authority required Treatment of HIV infection in patients over 12 years of age, weighing 40 kg or more, 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