Eltrombopag, tablets, 25 mg and 50 mg, (as olamine), Revolade® - March 2011
Page last updated: 01 July 2011
PDF printable version to Eltrombopag, tablets, 25 mg and 50 mg, (as olamine), Revolade®
(PDF 99 KB)
Public Summary Document
Product: Eltrombopag, tablets, 25 mg and 50 mg,
(as olamine), Revolade®
Sponsor: GlaxoSmithKline Australia Pty Ltd
Date of PBAC Consideration: March 2011
1. Purpose of Application
To request a Section 100 (Highly Specialised Drug) Public and
Private Hospital Authority Required listing for adult patients with
severe chronic immune (idiopathic) thrombocytopenic purpura
(ITP).
Highly Specialised Drugs are medicines for the treatment of chronic
conditions, which, because of their clinical use or other special
features, are restricted to supply to public and private hospitals
having access to appropriate specialist facilities.
2. Background
At the November 2010 meeting, the PBAC rejected a submission for eltrombopag on the
basis of uncertain clinical effectiveness in comparison with romiplostim.
The PBAC considered that the patient populations of the trials presented were not
representative of the more restricted high-risk subgroup of chronic ITP patients for
whom PBS listing was sought. In addition, the indirect comparison was based on post-hoc
analyses of the RAISE study. However, the PBAC acknowledged that, currently, these
are the only available data and that the recommendation to list romiplostim had been
made on the basis of the Kuter trials.
The PBAC considered that there were considerable concerns regarding the exchangeability
of the trials, arising from differences in the patient populations and the conduct
of the trials. On this basis, the appropriateness of an indirect determination of
the comparative treatment effect for eltrombopag and romiplostim, using these trials,
is uncertain.
A copy of the Public Summary Document from that meeting is available.
Registration Status
Eltrombopag olamine was TGA registered on 2 July 2010 for the treatment of adult patients
with chronic immune (idiopathic) thrombocytopaenic purpura (ITP) who have an inadequate
response or are intolerant to corticosteroids and immunoglobulins.
4. Listing Requested and PBAC’s View
Section 100 Public and Private hospital Authority Required
Note: Eltrombopag is not PBS-subsidised as an alternative to
splenectomy
Any queries concerning the arrangements to prescribe eltrombopag
may be directed to Medicare Australia on 1800 700 270 (hours of
operation 8 a.m. to 5 p.m EST Monday to Friday).
Written applications for authority to prescribe eltrombopag should
be forwarded to:
Medicare Australia
Prior Written Approval of Specialised Drugs
Reply Paid 9826
GPO Box 9826
HOBART TAS 7001
Further prescribing information is on the Medicare Australia
website at www.medicareaustralia.gov.au
Public and private hospital authority required
Initial (new patients)
Initial treatment, as the sole PBS-subsidised thrombopoietin
receptor agonist (TRA), of severe thrombocytopenia in an adult
patient with severe chronic immune (idiopathic) thrombocytopenic
purpura (ITP) who is:
Splenectomised and:
a. Has had an inadequate response to, or is intolerant to,
corticosteroid therapy post splenectomy; and
b. Has had an inadequate response to, or is intolerant to, immunoglobulin therapy post splenectomy;
OR
Not splenectomised and
c. Has had an inadequate response to, or is intolerant to, corticosteroid therapy at a dose equivalent to 0.5-2 mg/kg/day of prednisolone for at least 4-6 weeks; and
d. Has had an inadequate response to, or is intolerant to, immunoglobulin therapy; and
e. In whom splenectomy is contraindicated for medical reasons.
The following criteria indicate failure to achieve an adequate
response and must be demonstrated in all patients at the time of
initial application
a platelet count of ≤20 x 109/L.
OR
a platelet count of 20-30 x 109/L where the patient is
experiencing significant bleeding in this platelet range.
The authority application must be made in writing and must include:
- a completed authority prescription form,
- a signed patient acknowledgement,
- a completed Eltrombopag PBS Authority Application – Supporting Information form [may be downloaded from the Medicare Australia website (www.medicareaustralia.gov.au) ],
- a copy of a full blood count pathology report supporting the diagnosis of ITP, and
- where the application is sought on the basis of a medical contraindication to surgery, a signed and dated letter from the clinician making this assessment which includes the date upon which the patient was assessed for surgery and the clinical grounds upon which surgery is contraindicated.
The full blood count must be no more than 1 month old at the time
of application.
Public and private hospital authority required
Initial (grandfather patients)
Initial PBS-subsidised treatment, as the sole PBS-subsidised
thrombopoietin receptor agonist (TRA), of severe thrombocytopenia
in an adult patient with severe chronic immune (idiopathic)
thrombocytopenic purpura (ITP) who was receiving treatment with
eltrombopag prior to [listing date] and in whom the criteria for
initial treatment can be demonstrated to have been met at the time
eltrombopag was commenced:
The authority application must be made in writing and must include:
- a completed authority prescription form,
- a signed patient acknowledgement,
- a completed Eltrombopag PBS Authority Application – Supporting Information Form [may be downloaded from the Medicare Australia website (www.medicareaustralia.gov.au)],
- where the application is sought on the basis of a medical contraindication to surgery, a signed and dated letter from the clinician making this assessment which includes the date upon which the patient was assessed for surgery and the clinical grounds upon which surgery is contraindicated.
For patients whose dose of eltrombopag has been stable for at least
4 weeks at the time of the initial application for PBS-subsidy, the
medical practitioner should request a sufficient number of tablets
of appropriate strength based on the patient’s response to
initial therapy to provide 4 weeks treatment. Up to a maximum of 5
repeats may be authorised.
Where fewer than 5 repeats are initially requested with the
authority prescription, authority approvals for sufficient repeats
to complete a maximum of 24 weeks of treatment may be made by
telephone.
Authority approval will not be given for doses higher than 75 mg
per day.
Public and private hospital authority required
Continuing therapy or re-initiation after a break in therapy
First period of PBS-subsidised continuing treatment or
re-initiation of interrupted PBS-subsidised treatment, as the sole
PBS-subsidised thrombopoietin receptor agonist (TRA), of severe
thrombocytopenia in an adult patient with severe chronic immune
(idiopathic) thrombocytopenic purpura (ITP) who has displayed a
sustained platelet response to treatment with eltrombopag or
romiplostim during the initial period of PBS-subsidised
treatment.
For the purposes of this restriction, a sustained platelet response
is defined as:
a) use of rescue medication (corticosteroids or immunoglobulins) on
no more than one occasion during the initial period of
PBS-subsidised TRA therapy,
AND either of the following
a platelet count ≥50 x 109/L on at least four (4)
occasions, each at least one week apart;
OR
a platelet count >30 x 109/L and which is double the
baseline (pre-treatment) platelet count on at least four (4)
occasions, each at least one week apart.
Applications for the first period of continuing PBS-subsidised
treatment or re-initiation of interrupted treatment must be made in
writing and must include:
- a completed authority prescription form,
- a completed Eltrombopag PBS Authority Application – Supporting Information form [may be downloaded from the Medicare Australia website (www.medicareaustralia.gov.au) ],
- copies of the platelet count pathology reports (unless previously provided for patients re-initiating therapy).
The most recent platelet count must be no more than 1 month old at
the time of application.
The medical practitioner should request sufficient number of
tablets of appropriate strength based on the patient’s
response to initial therapy to provide 4 weeks treatment. Up to a
maximum of 5 repeats may be authorised.
Where fewer than 5 repeats are initially requested with the
authority prescription, authority approvals for sufficient repeats
to complete a maximum of 24 weeks of treatment may be made by
telephone.
Authority approval will not be given for doses higher than 75 mg
per day.
Public and private hospital authority required
Second and subsequent applications for continuing therapy
Continuing treatment, as the sole PBS-subsidised thrombopoietin
receptor agonist (TRA), of severe thrombocytopenia in an adult
patient with severe chronic immune (idiopathic) thrombocytopenic
purpura (ITP) who has previously received PBS-subsidised therapy
with eltrombopag or romiplostim and who continues to display a
response to treatment.
For the purposes of this restriction, a continuing response to
treatment with eltrombopag is defined as:
a) use of rescue medication (corticosteroids or immunoglobulins) on
no more than one occasion during the initial period of
PBS-subsidised TRA therapy,
AND either of the following
a platelet count ≥50 x 109/L;
OR
a platelet count >30 x 109/L and which is double the
baseline platelet count.
Platelet counts must be no more than 1 month old at the time of
application.
For PBAC’s view, see Recommendation and
Reasons.
5. Clinical Place for the Proposed Therapy
Chronic ITP is a long-term autoimmune disorder characterised by
persistently low platelet counts (thrombocytopenia) and cutaneous
and mucosal bleeding. Bleeding can range from mild (bruising and
purpura) to severe (intracranial or gastrointestinal haemorrhage)
and can sometimes result in death. The major therapeutic goal for
ITP is to increase platelet count to a safe level while minimising
treatment-related toxicity. First-line treatment typically involves
corticosteroids for asymptomatic patients with low platelet counts
or with mild bleeding symptoms, and high-dose corticosteroids,
intravenous immunoglobulin (IVIg) and/or platelet transfusions for
patients with clinically significant bleeding. Splenectomy is
recommended as second-line therapy.
The submission proposed eltrombopag as an alternative to
romiplostim for patients where splenectomy has failed or is
contraindicated and where patients are unresponsive/intolerant to
corticosteroids and IVIg therapy.
6. Comparator
The submission nominated romiplostim as the comparator. This was
previously accepted by the PBAC.
7. Clinical Trials
No new clinical data were presented in this submission compared to
the November 2010 submission. See November 2010 Public Summary
Document (PSD) for details.
8. Summary of Submission
The submission provided the following to address the PBAC’s concerns from the November 2010 meeting:
- Clarification of the proposed indication for eltrombopag;
- Additional information regarding the most likely therapeutic relativity between eltrombopag and romiplostim;
- A new price for eltrombopag;
- Updated estimates of the financial impact to government of listing eltrombopag at the reduced price; and
- Details of a proposed company-supported ITP registry project.
Cost offsets with Reductions in IVIg Use
The submission presented an indirect comparison of IVIg use based
on reported rates in the ITT populations.
The submission stated that although the point estimates generally
favour romiplostim, the confidence intervals are wide and do not
exclude the possibility of ‘no difference’ between
treatments. Factors which might bias the comparison of reductions
in IVIg use in favour of romiplostim include differences in patient
populations, the clinical setting and protocol restrictions on
allowable rescue medications.
Comparative Safety
The submission re-presented the same data from the original
submission but stated that in the eltrombopag trial, unlike the
romiplostim trial, bleeding events were assessed as efficacy
outcomes and the definition of an adverse event specifically
excluded ‘the disease/disorder being studied or expected
progression, signs or symptoms of the disease/disorder being
studied, unless more severe than expected for the subject’s
condition.’ Therefore, the extent of minor bleeding events
captured in the eltrombopag trial are likely to be significantly
reduced, which will bias the results of the indirect comparison in
favour of romiplostim. The submission also claimed that rates of
important non-bleeding events were similar among patients taking
the two drugs. However, the PBAC noted that there are also lower
rates of fatigue, arthralgia and contusion in the entire
eltrombopag trial population.
Equi-effective Doses of Eltrombopag and Romiplostim
The submission presented further analyses of the mean, median and
range of doses by patient category (ie splenctomised and
non-splenectomised patients who meet initiation and continuation
criteria) from the RAISE study.
The submission did not present a revised estimate of the
equi-effective doses. The November 2010 submission estimated the
equi-effective doses as eltrombopag 55.2 mg/day and romiplostim
276.2 mcg/day. The submission stated that the sponsor would support
an independent international disease database for newly diagnosed
adult patients with primary ITP and provided details of how this
might be implemented.
9. Estimated PBS Usage and Financial Implications
The submission presented revised estimates of the net cost to the
PBS and government health budgets, incorporating the revised price
for eltrombopag, revised (lower) market share assumptions and an
IVIg cost offset analysis.
The November 2010 submission estimated net PBS
savings per year to be less than $10 million in
Year 5.
The submission stated that, as previously shown in the original
submission, the revised financial analysis showed that listing
eltrombopag on the PBS as an alternative to romiplostim is expected
to result in significant cost savings to the PBS and government
health budgets.
For PBAC’s view, see Recommendation and
Reasons.
12. Recommendation and Reasons
The PBAC recommended listing on the basis of acceptable cost
effectiveness at the revised price (less effective and less
expensive compared with romiplostim) for patients with chronic
immune (idiopathic) thrombocytopenia purpura (ITP), restricted to
the same population as romiplostim. The PBAC acknowledged that the
data may suggest that eltrombopag is similar in safety and efficacy
to romiplostim in the post-splenectomy population, but this is not
the case in the non-splenectomised group.
With respect to the restriction, the PBAC recommended that patients
must achieve a satisfactory response with one or other of
eltrombopag or romiplostim within a 24 week period, during which
time switching is to be allowed. This will allow flexibility for
prescribers and patients to establish the most suitable treatment
for each individual within this period. Patients who fail treatment
after this 24 week period, regardless of whether exposed to
romiplostim, eltrombopag or both, will not be eligible for further
PBS-subsidised therapy with either of the drugs, unless the PBAC is
presented with evidence of effectiveness and cost effectiveness in
this situation.
The PBAC noted that use of IVIG may increase with the use of
eltrombopag compared with romiplostim.
The PBAC recommended that eltrombopag is not suitable for inclusion
in the PBS medicines for prescribing by nurse practitioners.
Recommendation:
ELTROMBOPAG, tablets, 25 mg and 50 mg, (as olamine)
Restriction:
Section 100 Public and Private Hospital Authority Required (Highly Specialised Drug)
Note:
Eltrombopag is not PBS-subsidised as an alternative to
splenectomy.
Any queries concerning the arrangements to prescribe eltrombopag
may be directed to Medicare Australia on 1800 700 270 (hours of
operation 8 a.m. to 5 p.m. EST Monday to Friday).
Written applications for authority to prescribe eltrombopag should
be forwarded to:
Medicare Australia
Prior Written Approval of Specialised Drugs
Reply Paid 9826
GPO Box 9826
HOBART TAS 7001
Further prescribing information is on the Medicare Australia
website at www.medicareaustralia.gov.au.
Authority Required
Initial (new patients)
Initial treatment, as the sole PBS-subsidised thrombopoietin
receptor agonist (TRA), of severe thrombocytopenia in an adult
patient with severe chronic immune (idiopathic) thrombocytopenic
purpura (ITP) who is:
(1) Splenectomised and:
(a) has had an inadequate response to, or is intolerant to,
corticosteroid therapy post splenectomy; and
(b) has had an inadequate response to, or is intolerant to,
immunoglobulin therapy post splenectomy;
OR
(2) Not splenectomised and:
(a) has had an inadequate response, or is intolerant to,
corticosteroid therapy at a dose equivalent to 0.5-2 mg/kg/day of
prednisone for at least 4-6 weeks; and
(b) has had an inadequate response, or is intolerant to,
immunoglobulin therapy; and
(c) in whom splenectomy is contraindicated for medical
reasons.
The following criteria indicate failure to achieve an adequate
response and must be demonstrated in all patients at the time of
initial application:
(a) a platelet count of less than or equal to 20,000 million per
L;
OR
(b) a platelet count of 20-30,000 million per L, where the patient
is experiencing significant bleeding or has a history of
significant bleeding in this platelet range.
The authority application must be made in writing and must
include:
(1) a completed authority prescription form,
(2) a signed patient acknowledgement,
(3) a completed Idiopathic Thrombocytopenic Purpura Initial PBS
Authority Application - Supporting Information Form [may be
downloaded from the Medicare Australia website
(www.medicareaustralia.gov.au)],
(4) a copy of a full blood count pathology report supporting the
diagnosis of ITP, and
(5) where the application is sought on the basis of a medical
contraindication to surgery, a signed and dated letter from the
clinician making this assessment which includes the date upon which
the patient was assessed for surgery and the clinical grounds upon
which surgery is contraindicated.
The full blood count must be no more than 1 month old at the time
of application.
A maximum of 24 weeks of treatment with eltrombopag will be
authorised under this criterion.
Note:
Patients will be able to trial either eltrombopag and/or
romiplostim within the initial 24 weeks treatment period. Patients
who fail to demonstrate a response to treatment with either
eltrombopag and/or romiplostim under the initial restriction will
not be eligible to receive further PBS-subsidised treatment with
either of these drugs.
No applications for increased repeats will be authorised.
MQ: 28
Rpts: 5
Authority Required
Initial (grandfather patients)
Initial treatment, as the sole PBS-subsidised thrombopoietin
receptor agonist (TRA), of severe thrombocytopenia in an adult
patient with severe chronic immune (idiopathic) thrombocytopenic
purpura (ITP) who was receiving treatment with eltrombopag prior to
[listing date] and in whom the criteria for initial treatment can
be demonstrated to have been met at the time eltrombopag was
commenced.
The authority application must be made in writing and must
include:
(1) a completed authority prescription form,
(2) a signed patient acknowledgement,
(3) a completed Idiopathic Thrombocytopenic Purpura Initial PBS
Authority Application - Supporting Information Form [may be
downloaded from the Medicare Australia website
(www.medicareaustralia.gov.au)], and
(4) where the application is sought on the basis of a medical
contraindication to surgery, a signed and dated letter from the
clinician making this assessment which includes the date upon which
the patient was assessed for surgery and the clinical grounds upon
which surgery is contraindicated.
A maximum of 24 weeks of treatment with eltrombopag will be
authorised under this criterion.
Note:
No applications for increased repeats will be authorised.
MQ: 28
Rpts: 5
Authority Required
Continuing therapy or re-initiation after a break in therapy
First period of PBS-subsidised continuing treatment or
re-initiation of interrupted PBS-subsidised treatment, as the sole
PBS-subsidised thrombopoietin receptor agonist (TRA), of severe
thrombocytopenia in an adult patient with chronic immune
(idiopathic) thrombocytopenic purpura (ITP) who has displayed a
sustained platelet response to treatment with eltrombopag during
the initial period of PBS-subsidised treatment.
For the purposes of this restriction, a sustained platelet response
is defined as:
(a) use of rescue medication (corticosteroids or immunoglobulins)
on no more than one occasion during the initial period of
PBS-subsidised eltrombopag,
AND either of the following:
(b) a platelet count greater than or equal to 50,000 million per L
on at least four (4) occasions, each at least one week apart;
OR
(c) a platelet count greater than 30,000 million per L and which is
double the baseline (pre-treatment) platelet count on at least four
(4) occasions, each at least one week apart.
Applications for the first period of continuing PBS-subsidised
treatment or re-initiation of interrupted treatment must be made in
writing and must include:
(1) a completed authority prescription form, and
(2) a completed Idiopathic Thrombocytopenic Purpura Continuing PBS
Authority Application - Supporting Information Form [may be
downloaded from the Medicare Australia website
(www.medicareaustralia.gov.au)],and
(3) copies of the platelet count pathology reports (unless
previously provided for patients re-initiating therapy).
The most recent platelet count must be no more than one month old
at the time of application.
A maximum of 24 weeks of treatment with eltrombopag will be
authorised under this criterion.
Where fewer than 5 repeats are initially requested with the
authority prescription, authority approvals for sufficient repeats
to complete a maximum of 24 weeks of treatment may be made by
telephone.
Note:
No applications for increased repeats will be authorised.
MQ: 28
Rpts: 5
Authority Required
Second and subsequent applications for continuing therapy
Continuing treatment, as the sole PBS-subsidised thrombopoietin
receptor agonist (TRA), of severe thrombocytopenia in an adult
patient with chronic immune (idiopathic) thrombocytopenic purpura
(ITP) who has previously received PBS-subsidised therapy with
eltrombopag and who continues to display a response to treatment
with eltrombopag.
For the purposes of this restriction, a continuing response to
treatment with eltrombopag is defined as:
(a) use of rescue medication (corticosteroids or immunoglobulins)
on no more than one occasion during the most recent 24 week period
of PBS-subsidised treatment with eltrombopag,
AND either of the following:
(b) a platelet count greater than or equal to 50,000 million per
L
OR
(c) a platelet count greater than 30,000 million per L and which is
double the baseline platelet count.
Platelet counts must be no more than 1 month old at the time of
application.
Authority applications for second and subsequent periods of
continuing therapy may be made by telephone by contacting Medicare
Australia on 1800 700 270 (hours of operation 8 a.m. to 5 p.m. EST
Monday to Friday).
Note:
No applications for increased repeats will be authorised.
MQ: 28
Rpts: 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 is satisfied with the PBAC decision. This decision will allow for consideration of the future listing of Eltrombopag for use in adult patients with severe chronic ITP as an important alternative medicine.