Imiquimod, cream 50 mg per g (5%), 250 mg single use sachets, 12, Aldara® , March 2009
Public summary document for Imiquimod, cream 50 mg per g (5%), 250 mg single use sachets, 12, Aldara®, March 2009
Page last updated: 03 July 2009
Public Summary Document
Product: Imiquimod, cream 50 mg per g (5%), 250 mg
single use sachets, 12, Aldara®
Sponsor: iNova Pharmaceuticals (Aust) Pty
Ltd
Date of PBAC Consideration: March 2009
1. Purpose of Application
To consider the findings of the Independent Review Report on
imiquimod.
2. Background
Imiquimod has been listed on the Pharmaceutical Benefits Scheme
(PBS) from 1 December 2006 for the treatment of superficial basal
cell carcinoma (sBCC).
At its July 2008 meeting, the PBAC rejected a request to extend the
PBS listing of imiquimod to include field therapy of multiple
clinically evident solar keratosis because of uncertain evidence of
effectiveness and safety over the comparator, 5-fluorouracil gel,
and the resulting uncertain cost-effectiveness.
Following the July 2008 rejection by the PBAC, the sponsor sought
an Independent Review.
3. Registration Status
Imiquimod 5% cream is registered for the treatment of solar
(actinic) keratosis on the face and the scalp, and primary
treatment of confirmed superficial basal cell carcinoma where
surgery is considered inappropriate, and the treatment of external
genital and peri-anal warts (Condyloma acuminata) in adults.
4. Listing Requested
The submission to the July 2008 PBAC meeting sought the following
listing:
Authority Required
Solar keratosis on the face or scalp in a patient with normal
immune function who has multiple clinically evident solar keratosis
lesions and requires topical drug treatment as field therapy.
NOTE:
The patient or carer must be able to understand and administer the
imiquimod dosing regimen.
No applications for increased maximum quantities and/or repeats
will be authorised.
5. Matters for Independent Review
The sponsor nominated the following issues on which the Review was
sought:
a) whether there is value in treating solar keratosis.
b) whether there is certainty in the comparative effectiveness of
imiquimod.
c) whether there is a safety issue with imiquimod as a true field
therapy.
d) whether imiquimod is a cost-effective therapy for solar
keratosis.
6. Findings of the Review
a Value in treating solar keratosis
The Review considered that there would be value in treating solar
keratosis if it prevented squamous cell carcinoma-related adverse
health outcomes, improved the quality of life for people with solar
keratoses and demonstrated long-term beneficial effects. The Review
found that it was not possible to assess imiquimod as a therapy to
prevent adverse health outcomes related to squamous cell carcinoma
due to the absence of supporting data. There have been no studies
that have examined quality-adjusted life years (QALYs) in relation
to solar keratosis. There was no reliable data on the duration of
the treatment effect after 16 months. It was concluded that it was
not possible to demonstrate that there was value in treating solar
keratosis.
The PBAC noted that the Review’s finding that there is a lack
of data to support the claims that treating solar keratosis with
imiquimod would reduce the malignancy potential or improve the
quality of life for people with solar keratosis.
b. Comparative effectiveness of imiquimod
The Review considered that imiquimod was superior to placebo in
reducing solar keratoses of the face and scalp. It was considered
that the sponsor’s claim of unequivocal superiority of
imiquimod over 5-flurouracil was not supportable due to the
limitations of the randomised controlled trial (Krawtchenko et al.,
2007) and the contradictory results from two Randomised Clinical
Trials (RCTs).
The PBAC noted the Review’s finding that there is no reliable
evidence to support a claim that imiquimod is superior to its
comparators, 5-flurouracil and cryotherapy.
c.Safety issues
The Review found that there was a lack of safety data for treatment
surface areas exceeding 25 cm2, which is consistent with
the opinion of the Therapeutic Goods Administration (TGA) and the
allowed treatment area in the TGA-approved prescriber information.
For treatment areas up to 25cm2 imiquimod has both local
and systemic side effects but these are usually within a clinically
acceptable range.
The PBAC noted the Review’s finding on this matter and that
patients could potentially apply the drug to a greater surface area
due to the amount of drug supplied (250 mg sachets) which could
treat a field up to 386cm2.
d. Cost-effectiveness of treating solar keratosis with
imiquimod
In the submitted economic evaluation, a cost effective analysis
using cost per patient-year in remission (either disease-free or
recurrence-free) over a three year timeframe was presented, in the
form of an incremental cost effectiveness ratio (ICER). The Review
concluded the cost effectiveness analysis used in the submission is
inadequate to demonstrate that imiquimod offers more of a given
health outcome than the main comparators largely due to a lack of
reliable data on relevant health outcomes, a lack of demonstrated
superiority over comparator therapies and inadequate study of the
durability of the treatment response.
Summary Opinion
The Review concluded the appropriate economic analysis is a
cost-minimisation analysis. A cost-minimisation analysis conducted
during the Review found that imiquimod was significantly more
expensive than its comparators, 5-flurouracil and
cryotherapy.
The PBAC noted the Review’s recommendation that the most
appropriate pharmaco-economic analysis is cost minimisation
analysis as imiquimod has not been demonstrated to be superior to
its comparators. The PBAC also noted that the Review found that
imiquimod is inferior to its comparators in terms of cost.
7. Recommendation and Reasons
The PBAC noted the findings of the Independent Review.
The PBAC noted the comment in the sponsor’s Pre-PBAC Response
that the PBAC should seek further advice from dermatologists in
making its decisions. The PBAC considered that further consultation
was inappropriate as it should base its decisions on evidence
presented at the time of the July 2008 submission.
The PBAC considered that the Review provided no new basis for the
Committee to reconsider its recommendation made at the July 2008
meeting.
8. 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.
9. Sponsor’s Comment
The Sponsor has no comments.
