Varenicline tartrate, tablet, 1 mg, Champix®, November 2009
Public Summary Document for Varenicline tartrate, tablet, 1 mg, Champix®, November 2009
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Public Summary Document
Product: Varenicline tartrate, tablet, 1
mg, Champix®
Sponsor: Pfizer Australia Pty Ltd
Date of PBAC Consideration: November 2009
1. Purpose of Application
To request the addition of a second continuing treatment
restriction to the current authority required listing to allow a
further 12 weeks of treatment for responders.
2. Background
At the July 2007 meeting, the PBAC recommended listing an authority
required 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 noted 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. However, the PBAC considered a further major
submission would be required to justify this additional treatment
period (which was not sought by the sponsor in its
application).
Listing was effective from 1 January 2008.
3. Registration Status
Varenicline tartrate was registered on 15 February 2007 for the following indication:
- as an aid to smoking cessation for adults over the age of 18 years.
4. Listing Requested and PBAC’s View
NOTE:
Only one course of PBS-subsidised varenicline tartrate will be
authorised per year. The period between commencing a course of
varenicline tartrate and bupropion hydrochloride must be at least 6
months. A course of treatment with varenicline tartrate 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.
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.
Authority Required
Continuation 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.
Additional listing criteria are proposed as follows:
Authority Required
Continuation of short-term, sole PBS-subsidised, therapy as an aid
to achieving long-term abstinence in a patient who has ceased
smoking as a result of a previously issued authority prescription
for this drug and who is enrolled in a comprehensive support and
counselling program.
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
The submission nominated placebo as the main comparator, which was
considered appropriate.
7. Clinical Trials
The submission presented one randomised, open-label trial (Trial
A3051035) comparing varenicline 1mg twice a day with placebo in
patients abstinent after an initial 12 weeks of treatment with
varenicline. At the end of the 12 weeks open-label varenicline
treatment 1236/1928 (64.1%) of patients remained abstinent from
smoking and were randomised to either placebo or a further 12 weeks
course of varenicline. This extended phase of the trial was
double-blinded. Thereafter, participants continued into a
non-treatment follow-up phase for an additional 28 weeks (for a
total of 52 weeks in the trial). The primary outcome of the trial
was carbon-monoxide confirmed continuous abstinence rate for weeks
13 to 24. The key secondary efficacy outcome was the continuous
abstinence rate from week 13 through week 52.
The table below details the published trial presented in the
submission:
| Trial ID / First author | Protocol title / Publication title | Publication citation |
| A3051035 Tonstad S, et al. | Effect of maintenance therapy with varenicline on smoking cessation. A randomized controlled trial. | JAMA, 2006; 296(1):64-71. |
8. Results of Trials
The primary outcome of Trial A3051035 (Continuous Abstinence Rate
(CA) from Week 13 through Week 24) and the key secondary outcome
relied upon in the modelled economic evaluation (Continuous
Abstinence Rate (CA) from Week 13 through Week 52) are summarised
in the tables below.
The primary outcomes results of Continuous Abstinence Rate
(CA) from Week 13 through Week 24 in Trial A3051035.
| Varenicline n/N (%) | Placebo n/N (%) | OR (95% CI) p-value | Absolute difference RD± (95% CI) p-value | Relative difference RR (95% CI) p-value | NNT (95% CI) |
| 425/602 (70.6%) | 301/604 (49.8%) | 2.47 (1.95, 3.15) p<0.0001 | 0.21 (0.15, 0.26) P<0.00001 | 1.42 (1.29, 1.56) P<0.00001 | 5 (4-7) |
There were significantly more smokers who quit after 12 weeks of
varenicline treatment, who maintained CA Week 13 to Week 24 than
placebo controls during an additional 12 weeks of treatment with
varenicline from (OR: 2.47 95% CI: 1.95, 3.15,
p-value<0.0001).
The key secondary outcome results of Continuous Abstinence
Rate from Week 13 through Week 52 in Trial A3051035.
| Varenicline n/N (%) | Placebo n/N (%) | OR (95% CI) p-value | Absolute Difference RD ± (95% CI) p-value | Relative Difference RR (95% CI) p-value | NNT (95% CI) |
| 265/602 (44.0%) | 224/604 (37.1%) | 1.35 (1.07, 1.70) P=0.0126 | 0.07 (0.01, 0.12) P=0.01 | 1.19 (1.03, 1.36) P=0.01 | 14 (8-71) |
Abbreviations: NNT=number needed to treat
The proportion of patients maintaining complete abstinence from
smoking from weeks 13 to 52 in the varenicline group who received
an additional 12 week course after successful completion of an
initial 12 week course, was 6.9 % higher than the placebo
group.
The most commonly reported adverse events (AEs) during open label
varenicline treatment were gastrointestinal (54.3%), psychiatric
(35.9%) and nervous system disorders (23%), of which nausea
(32.8%), insomnia (17.6%), abnormal dreams (14%) and headache
(12.7%) were the most common AEs from these broad system
classifications.
The submission provided additional data on potential safety
concerns of varenicline beyond those identified in the clinical
trials.
The submission acknowledged that from post-marketing data,
neuropsychiatric AEs, not previously identified in clinical trials,
are now recognised as a safety concern associated with varenicline.
The submission discussed the causality of psychiatric events and
the Sponsor’s risk management plans.
For PBAC’s view see Recommendation and Reasons.
9. Clinical Claim
The submission claimed an additional 12 weeks course of varenicline
as superior in terms of comparative effectiveness and inferior in
terms of comparative safety over placebo in patients who are
abstinent from smoking after an initial 12 weeks course of
varenicline. The PBAC accepted this claim.
10. Economic Analysis
The submission presented a stepped economic evaluation. The type of economic evaluation presented was a cost-utility analysis. The submission presented a decision analytic Markov model with time horizon of 19.77 years. The model compared two arms:
- no pharmacological treatment (placebo group)
- treatment with varenicline (varenicline group)
Three health states were possible in the model:
- smoker;
- ex-smoker;
- dead.
The perspective adopted for the analysis is that of the national
healthcare system. Thus drug costs and direct medical costs
associated with obtaining the drug are included in the analysis. In
sensitivity analyses, the additional costs of direct medical
treatment associated with a smoker, over and above those of an
ex-smoker, were also included.
The outcomes generated by the modelled evaluation are incremental
cost of varenicline versus placebo per additional life year gained
and per additional QALY gained. These outcomes were translated from
the Trial A3051035 outcome of Continuous Abstinence (CA) Rate Weeks
13 to 52.
The results of the sensitivity analyses indicate that the model is
most sensitive to variations in treatment efficacy results of
continued abstinence at Week 52. The incremental cost per extra
QALY gained (males and females) was calculated to be less than
$15,000.
For PBAC’s view see Recommendation and
Reasons.
11. Estimated PBS Usage and Financial Implications
The likely number of patients per year was estimated to be between
10,000 – 50,000 in year 1 and decreasing in year 5. This
estimation was considered to be underestimated.
Amended financial estimates in the Pre-Sub-Committee Response
estimated the cost to the PBS to be greater than $10 million in the
first year, decreasing to less than $10 million in year 5 of
listing.
For PBAC’s view see Recommendation and Reasons.
12. Recommendation and Reasons
The PBAC recommended the listing of varenicline tartrate tablets on
the PBS be extended to make available a second 12 week course for
patients who have successfully completed an initial 12 week course
of varenicline, but require a further 12 week course to aid in
maintaining abstinence, and who are enrolled in a comprehensive
support and counselling program, on the basis of an acceptable cost
effectiveness ratio. The PBAC accepted that varenicline is of
superior efficacy and inferior safety to placebo.
The PBAC advised that it would be appropriate for the Pricing
Authority to apply its usual methodology when considering the price
for this extension to listing, which has substantial financial
implications.
The PBAC noted the proportion of patients maintaining complete
abstinence from smoking in trial A3051035 from weeks 13 to 52 in
the varenicline group who received an additional 12 week course
after successful completion of an initial 12 week course, was 6.9 %
higher than the placebo group. The PBAC considered the absolute
difference, although relatively small, was a significant gain when
applied to the number of Australians currently smoking. The PBAC
noted that trial results represent a best case scenario as the
design of the trial maximises compliance, as the most responsive
and motivated individuals were selected for the double-blind phase.
In addition, education and counselling support were provided to
patients in the trial at the start of the second 12 weeks of
treatment, which also means that higher rates of abstinence are
likely to have been observed in the trial than would be expected in
clinical practice. The PBAC was concerned that patients with severe
chronic obstructive pulmonary disease, cardiovascular disease,
psychiatric illness or with a history of drug or alcohol abuse were
excluded from the trial, but would be included in the PBS eligible
population.
The PBAC considered the incremental cost of varenicline versus
placebo per additional QALY which was less than $15,000 to be
uncertain due to translation issues, but nevertheless
acceptable.
The PBAC considered the utilisation estimates in the submission to
be uncertain, however considered the estimates provided by the DUSC
likely to be towards the upper end of expenditure.
The PBAC expressed the view that education of prescribers on the
quality use of medicines (QUM) in smoking cessation is important
and requested the National Prescribing Service provide QUM
education, emphasising the importance of counselling support,
regarding this recommendation for varenicline.
Recommendation:
VARENICLINE
Amend NOTE to read:
NOTE:
The period between commencing varenicline tartrate and bupropion
hydrochloride must be at least 6 months. A course of treatment with
varenicline tartrate is 12 weeks or up to 24 weeks, if initial
treatment of 12 weeks has been successful. No increased maximum
quantities or repeats will be authorised. Clinical review is
recommended within 2 to 3 weeks of the initial prescription being
requested.
VARENICLINE, tablet, 1 mg (as tartrate)
Amend the current restriction as follows:
Restriction:
Authority Required
Continuation 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: 112
Repeats: nil
Authority Required
Completion of short-term, sole PBS-subsidised, therapy as an aid to achieving long-term abstinence after completion of an initial 12-week PBS-subsidised course in a patient who has ceased smoking, and who is enrolled in a comprehensive support and counselling program.
Maximum quantity: 56
Repeats: 2
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 a further 12 weeks of varenicline (Champix) treatment for patients who are abstinent after the first 12 weeks of treatment in order to increase the likelihood of long term abstinence. The Sponsor believes the availability of the additional 12 weeks of Champix will provide a further reduction in the significant health and economic burden associated with smoking in Australia.
