Methylnaltrexone bromide, injection, 12 mg in 0.6 mL (base), Relistor®, July 2009
Public summary document for Methylnaltrexone bromide, injection, 12 mg in 0.6 mL (base), Relistor®, July 2009
Page last updated: 30 October 2009
Public Summary Document
Product: Methylnaltrexone bromide, injection, 12
mg in 0.6 mL (base), Relistor®
Sponsor: Wyeth Australia Pty Ltd
Date of PBAC Consideration: July 2009
1. Purpose of Application
The submission sought an Authority required listing in the
Palliative Care Schedule for the treatment of opioid-induced
constipation in patients who have failed to respond to, or are
unable to tolerate laxative therapies.
2. Background
At the March 2009 meeting, the PBAC rejected an application to list
methylnaltrexone as an Authority required benefit in the Palliative
Care Schedule for initial and continuing treatment of
opioid-induced constipation in patients who have failed to respond
to, or are unable to tolerate laxative therapies, on the basis of a
high and uncertain cost-effectiveness ratio.
3. Registration Status
Methylnaltrexone was TGA registered on 13 November 2008 for the
treatment of opioid-induced constipation in patients with advanced
illness who are receiving palliative care when response to laxative
therapy has not been sufficient.
4. Listing Requested and PBAC’s View
Authority Required
For the treatment of opioid-induced constipation in palliative care
patients who have failed to respond to, or are unable to tolerate,
laxative therapies. Relistor may be prescribed for a maximum
duration of 4 months, no extensions will be granted. Relistor is
not subsidised for non-palliative care patients. Relistor is
administered as a single dose on alternate days, but may also be
given at longer intervals, as needed, on a PRN basis.
Authority Required
For the treatment of opioid-induced constipation in palliative care
patients who have failed to respond to, or are unable to tolerate,
laxative therapies. Relistor may be prescribed for a maximum
duration of 4 months, no extensions will be granted. Relistor is
not subsidised for non-palliative care patients. Relistor is
administered as a single dose on alternate days, but may also be
given at longer intervals, as needed, on a PRN basis.
The PBAC considered that restricting use of methylnaltrexone to a
maximum of 4 months treatment per patient was not practical as
palliative care patients may live longer but noted there was a high
clinical need and that treatment with methylnaltrexone was
effective in this group of patients.
5. Clinical Place for the Proposed Therapy
Methylnaltrexone will provide an alternative treatment for
opioid-induced constipation in palliative care patients where the
patient cannot tolerate or is not responding to other available
treatments.
6. Comparator
The submission nominated placebo as the main comparator. This did
not change from the March 2009 PBAC consideration.
7. Clinical Trials
Please refer to the March 2009 Public Summary Document
8. Results of Trials
Please refer to the March 2009 Public Summary Document.
9. Clinical Claim
The submission claimed that methylnaltrexone will benefit a
restricted, severely ill patient population by providing comfort
and dignity in the end of life situation.
10. Economic Analysis
The submission presented the economic model considered at the March
2009 PBAC meeting. The model took into account a revised price, and
calculated an ICER of $15,000 - $45,000 per QALY. Additional
cost-utility analyses using utility weights as a supplementary
analysis (derived from a study by Van den Haak et al (2008)) were
also presented. Using utility weights derived from this study, the
submission calculated an ICER of $45,000 – $75,000 per QALY.
The submission stated that the true ICER is likely to lie somewhere
between these two ICER values.
11. Estimated PBS Usage and Financial Implications
The financial cost per year to the PBS was estimated to be less
than $10 million in Year 5. The lower net costs to PBS were a
result of limiting treatment to four months (6 months in the
previous submission) and the revised price.
12. Recommendation and Reasons
The PBAC recommended listing methylnaltrexone on the PBS on the
basis of high clinical need, and high and uncertain but acceptable
cost-effectiveness compared with placebo.
The PBAC considered that restricting use of methylnaltrexone to a
maximum of 4 months treatment per patient was not practical as
palliative care patients may live longer but noted there was a high
clinical need and that treatment with methylnaltrexone was
effective in this group of patients.
The PBAC noted that at the new price proposed, the ICER range in
comparison with the ICER range from the March submission is lower.
An ICER between $45,000 and $75,000 was re-calculated using the Van
den Haak utility weights.
In March 2009, the PBAC identified several issues with the Schmier
utilities. The PBAC noted that the author of the paper from which
the utilities were derived did not endorse their use as utilities
as they are not consistent with standard utility estimation methods
and therefore could not be interpreted as QALY weights. The
re-submission presented the Van der Haak utilities that were
measured in patients with cancer. However, the PBAC considered that
there were several problems with use of the Van der Haak utilities.
These patients may be healthier than patients in the requested
population and did not use methylnaltrexone. The utility was 0.63
(median) (0.30-0.78) (inter-quartile range) for patients with no
constipation and 0.39 (0.19-0.69) for those with constipation.
These were assumed to be the appropriate utilities to apply
respectively to respondents and non-respondents/drop-outs from
treatment with methylnaltrexone. The PBAC considered that the
concerns in relation to the previous utility study about definition
of health states had been transferred to this study.
The PBAC considered that there is an issue regarding the
applicability of these health states to the requested listing as
the constipation health state is defined as respondents who use
laxatives and report constipation as a “bothersome
side-effect” of opioid use. The true “utilities”
with and without methylnaltrexone for the PBS population remain
uncertain. The PBAC considered that neither utility study provides
confidence about the true ICER of this treatment for this
population, however, noted that in this population it was unlikely
that there would be more information about true utilities.
Recommendation
METHYLNALTREXONE BROMIDE, injection, 12 mg in 0.6 mL (base)
Restriction:
Authority Required
Initial supply, in combination with oral laxatives, for a
palliative care patient with opioid-induced constipation who has
failed to respond to laxatives.
NOTE:
No applications for increased repeats will be authorised.
Max Qty: 3
Repeats: Nil
Authority Required
First continuing supply in combination with oral laxatives, for a
palliative care patient with opioid-induced constipation who has
demonstrated a response to methylnaltrexone.Second and subsequent
continuing supply in combination with oral laxatives, for a
palliative care patient with opioid-induced constipation who has
demonstrated a response to methylnaltrexone, and where consultation
with a palliative care specialist or service has
occurred.NOTE:
No applications for increased repeats will be authorised.
Max Qty: 7
Repeats: 3
Authority Required
Continuing supply for a palliative care patient with opioid-induced
constipation who has demonstrated a response to
methylnaltrexone.
NOTE:
No applications for increased repeats will be authorised.
Max Qty: 7
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
Wyeth welcomes this recommendation by the PBAC to list
methylnaltrexone as an alternative treatment option for palliative
care patients who have failed or are unable to tolerate oral
laxative therapies.
