Varenicline tartrate, tablets, 0.5 mg, 11 and 1 mg, 14 and 1 mg, 28 and tablets 1 mg, 56, (Champix), July 2007
Public summary document for Varenicline tartrate, tablets, 0.5 mg, 11 and 1 mg, 14 and 1 mg, 28 and tablets 1 mg, 56, (Champix), July 2007
Page last updated: 26 October 2007
PDF version of this page (PDF 42KB)
Public Summary Document
Product: Varenicline tartrate, tablets, 0.5 mg, 11 and 1 mg, 14 and 1 mg, 28 and tablets
1 mg, 56, Champix
Sponsor: Pfizer Australia Pty Ltd
Date of PBAC Consideration: July 2007
1. Purpose of Application
The submission sought authority required listings on the Pharmaceutical Benefits Scheme for short-term treatment to aid the goal of achieving abstinence in those patients aged 18 years and over who have indicated they are ready to cease smoking and meet specified criteria.
2. Background
This drug had not previously been considered by the PBAC.
3. Registration Status
Varenicline tartrate was registered by the TGA on 15 February 2007 as an aid for smoking
cessation in adults over the age of 18 years.
4. Listing Requested and PBAC’s View
NOTE:
Only one treatment course of varenicline per 12 months with no increased maximum quantities
or repeats will be authorised.
Authority required
Commencement of short-term treatment to aid the goal of achieving abstinence for adults
aged 18 years or over who have indicated that they are ready to cease smoking and:
a. who have entered a comprehensive support and counselling program; or
b. who are entering a comprehensive support and counselling program during the consultation at which this authority is requested. Details of the program must be specified in the authority application.
NOTE:
A follow-up visit to the requesting doctor is recommended within 2 to 3 weeks of the
original prescription being requested.
Authority required
Completion of short-term treatment to aid the goal of achieving abstinence for adults
who have indicated that they are ready to cease smoking and who are enrolled in a
comprehensive support and counselling program. Details of the program must be specified
in the original authority application.
For PBAC’s view, see Recommendation and Reasons.
5. Clinical Place for the Proposed Therapy
Smoking related illnesses are a significant public health problem. Smoking and nicotine addiction are strongly interrelated and it is therefore important to treat them as such when attempting to reduce smoking prevalence. Varenicline may assist those patients who are ready to quit smoking to do so, together with appropriate support mechanisms.
6. Comparator
Appropriately, the submission nominated bupropion as the main comparator.
7. Clinical Trials
The submission presented a meta-analysis of results from two double-blind randomised
trials (A3051028 and A3051036) comparing varenicline (1 mg twice daily after initial
titration), bupropion (150 mg twice daily after initial titration) and placebo in
smokers over 52 weeks. Subjects received 12 weeks of treatment with either varenicline
or bupropion, with follow up to 52 weeks.
These trials had been published at the time of submission, as follows:
|
Trial/First author |
Protocol title/Publication title |
Publication citation |
|---|---|---|
|
A3051028 |
Varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs. sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial. |
Journal of the American Medical Association. 296(1):47-55. |
|
A3051036 |
Efficacy of varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs. placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial. |
Journal of the American Medical Association. 296(1):56-63. |
8. Results of Trials
The results of the individual trials and the meta-analyses are summarised below.
Results of the primary outcome of four-week continuous quit rate from Weeks 9 to 12
for varenicline versus bupropion
The result for the primary outcome of four-week continuous quit rate from Weeks 9
to 12 was significant for both Trial A3051036 and Trial A3051028. The result of the
meta-analyses of the two trials was also significant for the primary outcome.
Results for the secondary outcome of continuous abstinence from Weeks 9 to 52 for
varenicline versus bupropion
The trials were also powered for the key secondary outcome, continuous abstinence
from Weeks 9 to 52. The results for the key secondary outcome of continuous abstinence
from Weeks 9 to 52 was significant for Trial A3051036 but not for Trial A3051028.
However, the result of the meta-analyses of the two trials was significant for continuous
abstinence from Weeks 9 to 52.
The submission presented the results of safety outcomes from the randomised trials
A3051028 and A3051036. Smokers receiving varenicline reported higher incidences of
nausea, abnormal dreams and headache compared to smokers randomised to bupropion.
Smokers receiving varenicline reported lower incidences of insomnia than smokers receiving
bupropion. These four adverse events may be clinically relevant as they could influence
patients’ compliance to continued therapy.
While the PBAC noted that significantly more patients on varenicline treatment experienced
nausea, abnormal dreams and headache compared with patients on bupropion, the Committee
accepted that the pooled rate of discontinuations due to adverse events was lower
with varenicline compared to bupropion (9.5% vs 13.9%; RR= 0.69 (0.47, 1.00)).
9. Clinical Claim
The submission described varenicline as having significant advantages in effectiveness
over bupropion and having similar or less toxicity.
See Recommendation and Reasons for the PBAC’s view.
10. Economic Analysis
The submission presented a stepped economic evaluation that progressed from a trial-based
analysis to a modelled analysis. The choice of the cost-effectiveness and cost-utility
approaches were considered appropriate. The resources included were drug costs and
GP costs.
Both the incremental cost-effectiveness ratios per additional life year gained and
per additional quality adjusted life year (QALY) versus bupropion were less than $15,000.
11. Estimated PBS Usage and Financial Implications
The submission estimated that in Year 1 of listing the likely number of patients per year would be > 200,000 and the likely financial cost per year to the PBS (excluding co-payments) minus any savings in use of other drugs would be in the range $60 - $100 million. The PBAC noted that the submission may have overestimated usage.
12. Recommendation and Reasons
The PBAC recommended listing on the PBS of varenicline as a short-term treatment to
aid smoking cessation on the basis of an acceptable cost-effectiveness compared with
bupropion. The PBAC considered that the incremental cost-effectiveness ratio of <$15,000
was acceptable for the higher quit and continuous abstinence rates demonstrated in
the meta-analyses of two head-to-head trials comparing varenicline to bupropion.
While the PBAC noted that significantly more patients on varenicline treatment experienced
nausea, abnormal dreams and headache compared with patients on bupropion, the Committee
accepted the sponsor’s comment that the pooled rate of discontinuations due to adverse
events was lower with varenicline compared to bupropion (9.5% vs 13.9%; RR= 0.69 (0.47,
1.00)).
The PBAC recommended that treatment is initiated with a four week course of varenicline,
with a further two months of treatment made available on a second authority prescription.
Further, concurrent treatment with bupropion should not be approved, and only one
course of either varenicline or bupropion per patient per 12 months should be approved.
The recommendation in the TGA approved Product Information that an additional 12 weeks
treatment be undertaken by patients who have successfully stopped smoking during the
first 12 weeks of treatment was noted, however, the PBAC considered a further major
submission would be required to justify this additional treatment period (which had
not been sought by the sponsor in its application).
The PBAC noted that the sponsor’s estimates may have overestimated usage, and requested
usage be monitored. The actions being undertaken by the sponsor in regard to the appropriate
use of varenicline, including the provision of counselling support via a sponsor-provided
Behavioural Modification Program were noted. However, the PBAC considered similar
requirements for counselling to those for bupropion should apply to varenicline, ie.
a specific counselling and support program is not mandated in the wording of the listing.
The PBAC recommended the 20 day safety rule should not apply.
Recommendation
VARENICLINE TARTRATE, tablets, 0.5 mg, 11 and 1 mg, 14 and 1 mg, 28 and tablets
1 mg, 56
NOTE:
Only one course of PBS-subsidised smoking cessation therapy (bupropion hydrochloride
or varenicline tartrate) will be authorised per year. A course of treatment with varenicline
is 12 weeks. No increased maximum quantities or repeats will be authorised. Clinical
review is recommended within 2 to 3 weeks of the original prescription being requested.
Restriction: Authority required
Commencement of short-term, sole PBS-subsidised, therapy as an aid to achieving abstinence
in a patient who has indicated they are ready to cease smoking and:
a. who has entered a comprehensive support and counselling program; or
b. who is entering a comprehensive support and counselling program during the consultation at which this authority is requested.
Details of the program must be specified in the authority application.
Maximum Quantity: 1 initiation pack (11 x 0.5mg, 14 x 1mg, 28 x 1mg)
Repeats: Nil
Restriction: Authority required
Completion of short-term, sole PBS-subsidised, therapy as an aid to achieving abstinence
in a patient who has previously been issued with an authority prescription for this
drug and who is enrolled in a comprehensive support and counselling program.
Maximum Quantity: 2 (56 x 1mg)
Repeats: Nil
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
Pfizer Australia (the Sponsor) welcomes the PBAC recommendation to list varenicline
(Champix) on the PBS for smoking cessation. The Sponsor believes the availability
of Champix with its superior cessation rates will help to reduce the significant health
and economic burden associated with smoking in Australia.
