Human Papillomavirus (Types 16 and 18) recombinant, AS04 adjuvanted vaccine, injection, 0.5 ml vial and pre-filled syringe, Cervarix, November 2007
Public summary document for Human Papillomavirus (Types 16 and 18) recombinant, AS04 adjuvanted vaccine, injection, 0.5 ml vial and pre-filled syringe, Cervarix, November 2007
Page last updated: 29 February 2008
Public Summary Document
Product: Human Papillomavirus (Types 16 and 18) recombinant, AS04 adjuvanted vaccine,
injection, 0.5 ml vial and pre-filled syringe, Cervarix
Sponsor: GlaxoSmithKline Australia Pty Ltd
Date of PBAC Consideration: November 2007
1. Purpose of Application
The re-submission sought to address the main areas of uncertainty considered by the PBAC at the July 2007 meeting. A revised economic model was presented that incorporated a revised price compared to the previous submission for consideration.
At its July 2007 meeting, the PBAC considered a submission seeking Cervarix listing on the National Immunisation Program (NIP) for the prophylactic vaccination of 12 and 13 year old girls (with a two-year catch up program for girls and women aged 13-26) against cervical cancer and precancerous lesions associated with HPV-16 and HPV-18. The PBAC rejected the application on the basis of uncertain cost-effectiveness against the comparator, Gardasil.. (See also Public Summary Document for July 2007)
3. Registration Status
Cervarix has been registered with the TGA since 18 May 2007. Cervarix is indicated
in females from 10 to 45 years for the prevention of cervical cancer by protecting
against incident and persistent infections, cytological abnormalities including atypical
squamous cells of undetermined significance (ASC-US) and cervical intraepithelial
neoplasia (CIN), CIN 1 and pre-cancerous lesions (CIN 2 and CIN 3) caused by HPV types
16 and 18. Immunogenicity studies have been conducted in females aged 10 to 14 years
and 26 to 45 years to link efficacy in females aged 15 to 25 years to other populations.
4. Listing Requested and PBAC’s View
The requested NIP indication was:
Prophylactic vaccination of 12 and 13 year old girls (with a two-year catch up program for girls and women aged 13-26) against cervical cancer and precancerous lesions associated with HPV-16 and HPV-18.
The PBAC had no objections to the requested wording of the restriction.
5. Clinical Place for the Proposed Therapy
Infection with human papillomavirus (HPV) has been clearly established as the central
cause of cervical cancer. In Australia, HPV-16 and HPV-18 account for approximately
70% of all cervical cancers and up to 50% of high-grade pre-cancerous lesions. Therefore,
an effective HPV-16/18 vaccine is expected to represent an important preventative,
primary health care intervention against cervical cancer and pre-cancerous cervical
Cervarix is a human papillomavirus vaccine that protects against infection caused by HPV-types 16 and 18.
There was no change to the comparator nominated previously.
7. Clinical Trials
As reported in the July 2007 Public Summary Document.
8. Results of Trials
As reported in the July 2007 Public Summary Document.
9. Clinical Claim
The re-submission was based on the conservative assumption that Cervarix is equivalent to Gardasil with respect to efficacy against cervical cancer caused by HPV-16/18 and that Gardasil offers the additional health benefit of protection against genital warts when compared to Cervarix. (see Sponsor comments)
10. Economic Analysis
The submission presented a revised economic model to address one of the key factors
that the PBAC considered at the July 2007 meeting, that is, the value of the health
loss associated with the lack of coverage against genital warts if Cervarix rather
than Gardasil is used. Hence, the re-submission proposed a different price compared
to the previous submission. This resulted in a cost saving in the range $45,000 -
$75,000 per QALY foregone.
11. Estimated PBS Usage and Financial Implications
No further PBS usage or financial analyses were included in the submission. The sponsor has indicated that it is willing to develop an appropriate risk sharing arrangement to address any uncertainties surrounding the inclusion of Cervarix on the NIP.
12. Recommendation and Reasons
The PBAC recalled that it had previously rejected a submission to list Cervarix on the NIP on the basis of uncertain cost-effectiveness against the comparator, Gardasil, noting the following:
- Cervarix was as effective as Gardasil in protection against the cancer-causing HPV types 16 and 18;
- There was uncertainty about the comparative efficacy of the two vaccines in terms of cross protection against other cancer-causing HPV types; and
- Gardasil offered protection against genital warts.
The PBAC considered that there continued to be uncertainty about the comparative efficacy of the two vaccines in terms of cross protection against other cancer-causing HPV types.
The submission provided a revised estimate of the incremental benefit that Gardasil offers over Cervarix through genital warts protection and the value of the health loss associated with the lack of coverage against genital warts if Cervarix rather than Gardasil is used.
The PBAC accepted that most of the assumptions in the economic model favoured Gardasil. The exception to this was the assumption of waning of Gardasil efficacy against genital warts. There were also residual concerns about equity, because individual patients are not offered a choice between vaccines, since decisions are made at the State level. However, given that all other assumptions did not favour Cervarix and there is a recognised need for more than one vaccine to be available in the event of supply shortages, the PBAC was prepared to accept that Cervarix is acceptably cost-effective at the new price and thus recommended the inclusion of Cervarix in the National Immunisation Program.
The PBAC also recommended that GSK provide the same contribution towards the national cervical screening program as has the sponsor of Gardasil and that it maintain a register of persons vaccinated. Further, in any risk-sharing agreement, the same conditions should apply concerning the possibility of a requirement for re-vaccination if the efficacy of the vaccine should wane.
List on the NIP for the prophylaxis against HPV-16 and HPV-18 of 12 and 13 year old girls (with a two-year catch up program for girls and women aged 13-26), with vaccination at 0, 1 month and 6 months.
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
GSK believes the PBAC has significantly undervalued the evidence of some cross-protection by Cervarix against infection caused by HPV-31 and HPV-45, and significantly overvalued the clinical and economic importance of the protection offered by Gardasil against genital warts.