Ibandronic Acid, tablet, 150 mg, Bonviva® Once Monthly, March 2007
Public summary documnet for Ibandronic Acid, tablet, 150 mg, Bonviva® Once Monthly, March 2007
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Public Summary Document
Product: Ibandronic Acid, tablet, 150 mg,
Bonviva® Once Monthly
Sponsor: Roche Products Pty Ltd
Date of PBAC Consideration: March 2007
1. Purpose of Application
The resubmission requested an authority required PBS listing for
the treatment of established postmenopausal osteoporosis in
patients with fracture due to minimal trauma.
2. Background
This was the second submission to PBAC for Bonviva Once Monthly.
At its July 2006 meeting, the PBAC rejected the submission because of the inadequate
evidence of demonstrating no difference between ibandronate and alendronate.
There is a Public Summary Document for the ibandronic acid application to the July 2006 PBAC meeting.
3. Registration Status
Bonviva Once Monthly was registered by the TGA on 4 July 2006 for
treatment of postmenopausal osteoporosis. Bonviva Once Monthly
increases BMD and reduces the risk of fractures. Osteoporosis may
be confirmed by the finding of low bone mass (at least 2.0 SD below
the normal mean) or by the presence or history of osteoporotic
fracture.
4. Listing Requested and PBAC’s View
Authority Required
Initial treatment as the sole PBS-subsidised anti-resorptive agent
for established postmenopausal osteoporosis in patients with
fracture due to minimal trauma. The fracture must have been
demonstrated radiologically and the year of plain x-ray or CT-scan
or MRI scan must be included in the authority application.
A vertebral fracture is defined as a 20% or greater reduction in
height of the anterior or mid portion of the vertebral body
relative to the posterior height of that body, or, a 20% or greater
reduction in any of these heights compared to the vertebral body
above or below the affected vertebral body;
Continuing treatment as the sole PBS-subsidised anti-resorptive
agent for established postmenopausal osteoporosis in patients with
fracture due to minimal trauma, where the patient has previously
been issued with an authority prescription for this drug.
See Recommendation and Reasons for the PBAC’s
views.
5. Clinical Place for the Proposed Therapy
In the treatment of postmenopausal osteoporosis, ibandronic acid
provides an alternative treatment to other bisphosphonates and
raloxifene.
6. Comparator
The comparator, as previously agreed by the PBAC, was alendronate
70 mg/week once weekly.
7. Clinical Trials
The submission made no changes to the trial data presented in the
previous submission to the July 2006 meeting, with the exception of
the addition of one year data in the MOBILE Long Term Extension
(LTE) Study, and the inclusion of results of the intermittent
dosing regimens in the BONE study (20 mg ibandronic acid) and the
MOBILE study (100 mg ibandronic acid).
The evidence provided in the re-submission, was a distant indirect
comparison:
Stage 1:
- 150mg ibandronate taken once monthly is non-inferior to 2.5mg ibandronate taken daily (MOBILE trial, based on BMD outcomes)
- 70mg alendronate, taken once per week is non-inferior to 10mg alendronate daily (Schnitzer and Rizzoli trials, based on BMD outcomes)
Stage 2:
- 2.5mg ibandronate taken daily vs. placebo (BONE trial, fracture data)
- 10mg alendronate daily vs. placebo (FIT and Liberman trials, fracture data)
8. Results of Trials
For new vertebral fractures, new or worsening fractures and new
clinical vertebral fractures, both ibandronic acid 2.5 mg/day and
alendronate 10 mg/day were statistically superior to placebo. The
indirect comparison results suggested that there was no
statistically significant difference between the drugs in reducing
the risk of each type of fracture. However, for new clinical
vertebral fracture, the results were consistent with a possible
increased risk with ibandronic acid. For new vertebral fractures,
the baseline risk between the populations of the BONE and
FIT/Liberman trials were different, as shown by the placebo arms of
those trials (8.1% vs. 18.5%) raising the possibility that there
might be important differences between studies which increased the
uncertainty of the results from the indirect comparison. A similar
observation was made for the placebo arms in the analysis of new or
worsening vertebral fractures (8.9% vs. 18.5%), but not for new
clinical vertebral fractures.
The PBAC accepted the arguments presented in the sponsor’s
Pre-PBAC response that the BONE study population had a lower risk
of fracture than those of other similar studies, including the FIT
study.
The three year efficacy and safety data were presented for the
MOBILE long term extension (LTE) study. Overall adverse events were
similar between the ibandronic acid 150 mg/month and ibandronic
acid 100 mg/month doses in the MOBILE LTE study. The PBAC noted the
approved Product Information for ibandronic acid now contains
warnings regarding osteonecrosis of the jaw (ONJ) and adynamic bone
disease (ABD). The warnings suggest that this is more a class
effect rather than directly related to ibandronic acid.
9. Clinical Claim
The submission claimed that ibandronic acid 150 mg/month was no
worse than alendronate 70 mg/week.
See Recommendation and Reasons for PBAC’s
views.
10.Economic Analysis
The submission provided an updated preliminary (trial-based)
economic evaluation. A cost-minimisation approach was presented in
this resubmission on the basis that ibandronic acid 150 mg/monthly
and alendronate 70 mg/weekly were equi-effective doses.
11.Estimated PBS Usage and Financial Implications
The likely number of patients was estimated to be between 100,000 -
200,000 in Year 5 of listing accounting for market share.
The estimated financial cost per year to the PBS (excluding
co-payments) was > $100 million per year in Year 5 for all
bisphosphonates. The net cost of ibandronic acid to the PBS after
subtracting patient co-payments is < $10 million per year in
year 5 of listing.
The estimates of costs to the PBS were based on the assumption that
there would be no additional increase in the usage of
bisphosphonates, as ibandronic acid would be substituted for
existing bisphosphonates (predominantly alendronate) and therefore
there will be minimal net impact to PBS expenditure.
12.Recommendation and Reasons
The PBAC recommended listing on a cost-minimisation basis with
alendronate for the treatment of established osteoporosis, with the
equi-effective doses being ibandronic acid 150 mg/month and
alendronate 70 mg/week. The pricing calculation is to be based on
12 doses of ibandronic acid, with each dose given on a calendar
monthly basis, being equivalent to 52 doses of alendronate, with
each dose given on a weekly basis.
The PBAC recommended the 20 day safety net rule should apply on the
basis that the rule does apply to other PBS listed
bisphosphonates.
Recommendation
Ibandronic acid, tablet, 150 mg,
Authority Required
Initial treatment as the sole PBS-subsidised anti-resorptive agent
for established postmenopausal osteoporosis in patients with
fracture due to minimal trauma. The fracture must have been
demonstrated radiologically and the year of plain x-ray or CT-scan
or MRI scan must be included in the authority application.
A vertebral fracture is defined as a 20% or greater reduction in
height of the anterior or mid portion of the vertebral body
relative to the posterior height of that body, or, a 20% or greater
reduction in any of these heights compared to the vertebral body
above or below the affected vertebral body;
Continuing treatment as the sole PBS-subsidised anti-resorptive
agent for established postmenopausal osteoporosis in patients with
fracture due to minimal trauma, where the patient has previously
been issued with an authority prescription for this drug.
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.
