Fluticasone propionate with salmeterol xinafoate, oral pressurised inhalation 250 micrograms-25 micrograms (base) per dose (120) doses, CFC-free formulation, powder for oral inhalation in breath actuated device 500 micrograms- 50 micrograms (base) per dose(60), Seretide MDI 250/25®, Seretide Accuhaler 500/50®, March 2007
Public summary document for Fluticasone propionate with salmeterol xinafoate, oral pressurised inhalation 250 micrograms-25 micrograms (base) per dose (120) doses, CFC-free formulation, powder for oral inhalation in breath actuated device 500 micrograms- 50 micrograms (base) per dose(60), Seretide MDI 250/25®, Seretide Accuhaler 500/50®, March 2007
Page last updated: 29 June 2007
Public Summary Document
Product: Fluticasone propionate with salmeterol
xinafoate, oral pressurised inhalation 250 micrograms-25 micrograms
(base) per dose (120) doses, CFC-free formulation, powder for oral
inhalation in breath actuated device 500 micrograms- 50 micrograms
(base) per dose(60), Seretide MDI 250/25®, Seretide Accuhaler
500/50®
Sponsor: GlaxoSmithKline Australia Pty Ltd
Date of PBAC Consideration: March 2007
1. Purpose of Application
To extend the restricted benefit listing of the highest strengths
of Seretide MDI and Accuhaler to include the long-term maintenance
treatment of chronic obstructive pulmonary disease (COPD) in
patients with a history of repeated exacerbations.
2. Background
Seretide was first considered by the PBAC in March 2000. The PBAC
recommended the listing of Seretide at its March 2000 meeting as a
Restricted Benefit for patients who previously had frequent
episodes of asthma while receiving treatment with oral
corticosteroids or optimal doses of inhaled corticosteroids and who
are stabilised on concomitant inhaled salmeterol xinafoate and
fluticasone propionate.
3. Registration Status
Seretide (for COPD) is registered by the TGA for the symptomatic
treatment of patients with severe COPD (FEV1<50% predicted
normal) and a history of repeated exacerbations who have
significant symptoms despite regular beta-2 agonist bronchodilator
therapy. Seretide is not indicated for the initiation of
bronchodilator therapy in COPD.
4. Listing Requested and PBAC’s View
Restricted benefit
For the long-term maintenance treatment of chronic obstructive
pulmonary disease in patients who have a history of repeated
exacerbations.
See Recommendation and Reasons for the PBAC’s
view
5. Clinical Place for the Proposed Therapy
Seretide will provide an alternative therapy to tiotropium for
patients with chronic obstructive pulmonary disease with a history
of repeated exacerbations.
6. Comparator
The submission nominated tiotropium bromide monohydrate as the main
comparator, which was considered appropriate by the PBAC.
7. Clinical Trials
The submission provided one key randomised trial comparing Seretide
(fluticasone 500 mcg with salmeterol 50 mcg twice daily) with
tiotropium 18 mcg once daily in patients with COPD over 104 weeks.
Two supportive trials comparing the same drugs in a similar
population over 12 weeks and 3 weeks respectively were also
provided.
None of the trials were published at the time of the
submission.
8. Results of Trials
There was no statistically significant difference in the rate of
health care utilisation exacerbations, the primary outcome of the
trial, between treatments. All-cause mortality, one of the safety
outcomes in the trial, had been relied on in the economic
evaluations.
There were more death events in the tiotropium group than in the
Seretide group. The majority of the fatalities were associated with
cardiac disorders, with a greater percentage occurring in the
tiotropium group compared with the Seretide group.
The PBAC noted there was a small possibility that over this short
time period, potentially improved management of COPD with Seretide
may have impacted on the general health of these patients (both
Seretide and tiotropium provide symptom control, although do not
affect the COPD disease process), resulting in a lower all-cause
mortality rate.
The PBAC considered that there was no plausible biological
mechanism to support such a difference. Further, the all cause
mortality data could be considered an unexpected finding because
the trial had not predefined the hypothesis that Seretide has a
role in the prevention of mortality in patients with COPD.
9. Clinical Claim
The submission claimed that Seretide is more effective than
tiotropium bromide monohydrate with similar toxicity.
See Recommendations and Reasons for PBAC’s
view.
10. Economic Analysis
A preliminary economic evaluation was presented. The choice of the
cost-effectiveness approach was not considered valid as the PBAC
did not accept the clinical claim of superior effectiveness. The
resources included in the evaluation were the costs of study drugs,
concomitant medications, and COPD-related health care resources
other than medications.
The trial-based incremental discounted cost per extra discounted
life-year gained was less than $15,000.
The trial-based incremental discounted cost per extra discounted
responder gained was also less than $15,000.
A modelled economic evaluation was presented adopting a
cost-utility approach. As in the preliminary economic evaluation,
the total resources consumed and the outcomes observed within the
trial period of two years are used in the economic evaluation. The
only difference from the preliminary economic evaluation was that
utility weights have been generated by mapping scores from the St
George’s Respiratory Questionnaire to EQ5D values, using
Ordinary Least Squares Regression. The PBAC noted that as COPD is a
chronic condition that needs long-term treatment, the costs and
effectiveness observed within two years may not be adequate to
predict the long-term cost-effectiveness.
The base case modelled incremental discounted cost per extra
discounted quality-adjusted life-year was less than $15,000.
11. Estimated PBS Usage and Financial Implications
The net financial cost per year to the PBS (after off-sets in the
use of substituted drugs) was estimated to be less than $10
million.
12. Recommendation and Reasons
The PBAC recommended a restricted benefit listing on a
cost-minimisation basis with the equi-effective doses being
fluticasone 500 mcg/salmeterol 50 mcg inhaled twice daily being
equivalent to tiotropium bromide monohydrate 18 mcg inhaled once
daily in the treatment of COPD. The recommended restriction
reflects the wording of the TGA registered indication.
The PBAC did not accept the claim that fluticasone propionate with
salmeterol xinafoate had significant advantages in terms of
clinical effectiveness and toxicity over tiotropium. The PBAC
considered that the all-cause mortality data could be considered an
unexpected finding because this was a positive secondary outcome
when the primary outcome analysis showed no statistically
significant difference between treatment groups and the trial had
not predefined the hypothesis that Seretide has a role in the
prevention of deaths in patients with COPD. Therefore, its use as
the foundation of an economic claim was not appropriate.
In the Pre-PBAC response, the sponsor advised it would be willing
to accept a therapeutic relativity of no difference in
effectiveness and safety between Seretide and tiotropium, based on
the results of the trial 40036.
Recommendation
FLUTICASONE PROPIONATE with SALMETEROL XINAFOATE, oral pressurised
inhalation 250 micrograms-25 micrograms (base) per dose (120)
doses, CFC-free formulation, powder for oral inhalation in breath
actuated device 500 micrograms- 50 micrograms (base) per
dose(60)
Add the following to the current listings:
Restricted benefit
Symptomatic treatment of chronic obstructive pulmonary disease
(COPD) where, the FEV1 is <50% predicted normal, and there is a
history of repeated exacerbations with significant symptoms despite
regular beta-2 agonist bronchodilator therapy.
NOTE:
Seretide is not indicated for the initiation of bronchodilator
therapy in COPD.
Maximum Quantity:1
Repeats:5
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
The sponsor chose not to make a comment.
