Topiramate, tablets, 25 mg and 50 mg, Topamax®, March 2007
Public summary document for Topiramate, tablets, 25 mg and 50 mg, Topamax®, March 2007
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Public Summary Document
Product: Topiramate, tablets, 25 mg and 50 mg,
Topamax®
Sponsor: Janssen-Cilag Pty Ltd
Date of PBAC Consideration: March 2007
1. Purpose of Application
This re-submission sought to add to the current listing for
epilepsy, an authority required listing for the prophylactic
treatment of migraine for the 25 mg and 50 mg strengths only.
2. Background
Topiramate was first listed on the PBS in August 1997 with an
authority required listing for the treatment of partial epileptic
seizures which are not controlled satisfactorily by other
anti-epileptic drugs. The restriction was amended in March 2000 to
include primarily generalised tonic-clonic epileptic seizures and
seizures of the Lennox-Gastaut syndrome.
A submission for an authority required listing for the prophylactic
treatment of migraine in patients who had tried beta-blockers and
pizotifen was considered by the PBAC at its July 2006 meeting. The
PBAC rejected the submission because of uncertain benefit in the
population in whom listing was requested and the resulting
uncertain cost-effectiveness. The PBAC was concerned that overlap
between the trial population and the population for whom PBS
listing was sought was likely to be minimal.
3. Registration Status
Topiramate tablets (25 mg, 50 mg, 100 mg, and 200 mg) and sprinkle
capsules (15 mg, 25 mg and 50 mg) are registered by the TGA for
prophylaxis of migraine headache in adults.
4. Listing Requested and PBAC’s View
Authority required
Initial treatment
Prophylaxis of migraine in an adult who has experienced an average
of three or more migraines per month over a period of at least six
months, and who:
(a) has a contraindication to beta-blockers, as described in the
relevant TGA-approved Product Information; OR
(b) has experienced intolerance of a severity necessitating
permanent withdrawal during treatment with a beta-blocker;
AND
(c) has a Body Mass Index (BMI) >30 kg/m2; OR
(d) has experienced intolerance of a severity necessitating
permanent withdrawal during treatment with pizotifen.
Details of the contraindication and/or intolerance(s) and/or BMI
must be provided at the time of application.
Continuing treatment
Continuing treatment for patients who have previously received PBS
subsidised treatment with topiramate for prophylaxis of
migraine.
See Recommendation and Reasons for PBAC’s
view.
5. Clinical Place for the Proposed Therapy
For use in migraine prophylaxis in patients who are unable to take
other treatments (beta blockers and pizotifen).
6. Comparator
The submission nominated placebo as the comparator and this was
previously agreed by the PBAC at its July 2006 meeting.
7. Clinical Trials
The submission presented the same two randomised trials as in the
previous submission (Silberstein et al 2004 and Brandes et al 2004)
as key evidence, in which topiramate 50 mg/day, 100 mg/day and 200
mg/day were compared with placebo respectively in migraine patients
over 26 weeks.
The re-submission removed the trial Silvestrini et al (2003), as
the population who have failed previous prophylactic medications
was no longer applicable to the requested restriction in this
re-submission.
The trials were published at the time of the submission as follows:
| Trial/First author | Protocol title/Publication title | Publication citation |
| Silberstein JD | A randomized, double-blind, placebo-controlled, parallel group, dose-response study to evaluate the efficacy and safety of topiramate in the prophylaxis of migraine | Archives of Neurology, 2004:61, no. 4;490-495. |
| Brandes JL | A randomized, double-blind, placebo-controlled, parallel-group, dose-response study to evaluate the efficacy and safety of topiramate in the prophylaxis of migraine. | Journal of the American Medical Association, 2004:291, no. 8;965-973. |
8. Results of Trials
The pooled analysis of the primary efficacy outcome, change in
average monthly migraine period rate showed that topiramate 100
mg/day was statistically significantly superior to placebo.
The average monthly migraine period rate was defined as the total
number of migraine periods during a phase, divided by the total
duration of that phase (in days), times 28. Migraine periods were
defined as the length of time between the onset and cessation of
painful migraine symptoms. The duration of this period could last
up to, but no longer than 24 hours. If symptoms ended and recurred
within 24 hours of the onset, they were considered part of the
initial migraine period. Any symptoms lasting beyond 24 hours of
the initial onset were considered to be part of a new, distinct
migraine period.
9. Clinical Claim
The submission described topiramate as having significant
advantages in effectiveness over placebo but more toxicity.
See Recommendation and Reasons for PBAC’s
view.
10. Economic Analysis
An updated preliminary economic evaluation was presented. The
approach in the preliminary economic evaluation remained
unchanged.
The trial-based incremental cost/extra responder gained was
estimated to be <$15,000. The trial-based incremental cost/extra
migraine day avoided was estimated to be <$15,000.
An updated modelled economic evaluation was presented. The approach
and structure of the modelled economic evaluation were unchanged
from the previous submission.
The base case modelled incremental cost/extra QALY was estimated to
be in the range $15,000 -$45,000.
11. Estimated PBS Usage and Financial Implications
The submission stated that the likely number of patients/year would
be in the range 10,000 to 50,000 in Year 5 of listing. The PBAC
considered that this is a likely under-estimate in the
submission.
The submission estimated that the financial cost/year to the PBS
would be up to between $10 million to $30 million in Year 5 of
listing.
12. Recommendation and Reasons
The PBAC recommended listing on the basis of acceptable
cost-effectiveness compared to placebo for migraine prophylaxis in
patients unable to take a beta-blocker and/or pizotifen.
The PBAC was concerned about the risk of use beyond the requested
restriction to first line therapy for migraine prophylaxis and to
neuropathic pain and that this presented a high degree of financial
risk for government. The PBAC thus considered that an authority
required listing would be appropriate.
Recommendation
TOPIRAMATE, tablets, 25 mg and 50 mg
Authority required
Initial treatment
Prophylaxis of migraine in a patient who has experienced an average
of three or more migraines per month over a period of at least six
months, and who:
a)has a contraindication to beta-blockers, as described in the
relevant TGA-approved Product Information; OR
b) has experienced intolerance of a severity necessitating
permanent withdrawal during treatment with a beta-blocker;
AND
(c) is overweight (as defined by body mass index of ≥30 kg/m2);
OR
(d) has experienced intolerance of a severity necessitating
permanent withdrawal during treatment with pizotifen.
Details of the contraindication and/or intolerance(s) and/or body
mass index must be provided at the time of application.
Continuing treatment
Continuing treatment for patients who have previously received PBS
subsidised treatment with topiramate for prophylaxis of
migraine.
Maximum Quantity: 60 (tablets 25 and 50 mg only)
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 welcomes this decision by the PBAC to provide access to
an alternative migraine prophylactic agent.
