Methoxy polyethylene glycol-epoetin beta, solution for injection, 30 micrograms in 0.3 mL, 50 micrograms in 0.3 mL, 75 micrograms in 0.3 mL, 100 micrograms in 0.3 mL, 120 micrograms in 0.3 mL, 200 micrograms in 0.3 mL and 360 micrograms in 0.6 mL, single use pre-filled syringe, Mircera®, November 2009
Public Summary Document for Methoxy polyethylene glycol-epoetin beta, solution for injection, 30 micrograms in 0.3 mL, 50 micrograms in 0.3 mL, 75 micrograms in 0.3 mL, 100 micrograms in 0.3 mL, 120 micrograms in 0.3 mL, 200 micrograms in 0.3 mL and 360 micrograms in 0.6 mL, single use pre-filled syringe, Mircera®, November 2009
Page last updated: 05 March 2010
Public Summary Document
Product: Methoxy polyethylene glycol-epoetin beta,
solution for injection, 30 micrograms in 0.3 mL, 50 micrograms in
0.3 mL, 75 micrograms in 0.3 mL, 100 micrograms in 0.3 mL, 120
micrograms in 0.3 mL, 200 micrograms in 0.3 mL and 360 micrograms
in 0.6 mL, single use pre-filled syringe,
Mircera®
Sponsor: Roche Products Pty Limited
Date of PBAC Consideration: November
2009
1. Purpose of Application
To request a Section 100 (Highly Specialised Drugs Program) listing
for treatment of anaemia requiring transfusion, defined as a
haemoglobin level of less than 100 g per litre, where intrinsic
renal disease, as assessed by a nephrologist, is the primary cause
of the anaemia.
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
This drug had not previously been considered by the PBAC.
3. Registration Status
Methoxy polyethylene glycol-epoetin beta was registered by the TGA
on 28 July 2009 for the treatment of anaemia associated with
chronic kidney disease (CKD).
4. Listing Requested and PBAC’s View
Section 100 (Highly Specialised Drugs) Private hospital
authority required
Treatment of anaemia requiring transfusion, defined as a
haemoglobin level of less than 100g per litre, where intrinsic
renal disease, as assessed by a nephrologist, is the primary cause
of the anaemia.
For PBAC’s view see Recommendation and
Reasons.
5. Clinical Place for the Proposed Therapy
Chronic kidney disease (CKD) is marked by long-term and usually
irreversible loss of kidney function and may further deteriorate
into end-stage kidney disease, and renal replacement therapy in the
form of dialysis or transplantation is required for survival.
Anaemia is a complication of chronic kidney disease.
Methoxy polyethylene glycol-epoetin beta would provide an
alternative treatment for anaemia associated with CKD.
6. Comparator
The submission nominated darbepoetin alfa as the main comparator
and epoetin alfa and epoetin beta as the secondary comparators. The
PBAC considered this appropriate.
7. Clinical Trials
The submission presented six randomised trials comparing methoxy
polyethylene glycol-epoetin beta (MPGE) and existing Erythropoiesis
Stimulating Agents (ESAs) over 24 to 36 weeks in patients with
anaemia of chronic kidney disease. Two are correction trials
(BA16736, BA16738) in pre-dialysis patients or patients new to
dialysis, and four are maintenance trials (BA16739, BA16740,
BA17283, BA17284) in patients already on treatment with an existing
ESA. Two trials (BA16738, BA17283) used darbepoetin as control, and
the other four trials used epoetin alfa or beta.
The table below details the published trials presented in the
submission:
| Trial ID / First author | Protocol title / Publication title | Publication citation |
| Direct randomised trials | ||
| BA16736 Klinger M,et al | Efficacy of intravenous methoxy polyethylene glycol-epoetin beta administered every 2 weeks compared with epoetin administered 3 times weekly in patients treated by haemodialysis or peritoneal dialysis: A randomised trial | American Journal of Kidney Disease 2007;50(6):989-1000 |
| BA16738 Macdougall IC, et al. | CERA corrects anaemia in patients with chronic kidney disease not on dialysis: results of a randomised clinical trial. | Clinical Journal of the American Society of Nephrology 2008;3(2):337-347 |
| BA16739 Levin NW, et al | Intravenous methoxy polyethylene glycol-epoetin beta for haemoglobin control in patients with chronic kidney disease who are on dialysis: a randomised non-inferiority trial (MAXIMA). | Lancet 2007;370:1415-1421 |
| BA16740 Sulowicz W, et al. | Once-monthly subcutaneous CERA maintains stable haemoglobin control in patients with chronic kidney disease on dialysis and converted directly from epoetin one to three times weekly. | Clinical Journal of the American Society of Nephrology 2007;2: 637-646 |
| BA17283 Canaud B, et al. | Intravenous CERA maintains stable haemoglobin levels in patients on dialysis previously treated with darbepoetin alfa: results from STRIATA, a randomised phase III study. | Nephrology Dialysis Transplantation 2008;23:3654-3661 |
| B17284 Spinowitz B, et al. | CERA maintains stable control of haemoglobin in patients with chronic kidney disease on dialysis when administered once every two weeks. | American Journal of Nephrology 2008;28 (2):280-289 |
8. Results of Trials
The primary outcome in the correction trials was the proportion
with a haemoglobin response (defined as a Hb increase of at least
1.0 g/dL to a level of at least 11 g/dL). The primary outcome in
the maintenance trials was a change in Hb level; differences
between MPGE and other ESAs were tested using a non-inferiority
margin of -0.75 g/dL. Results were pooled using a random effects
meta-analysis. Trial BA16738 used both Hb response rate and change
in Hb as primary outcomes.
There were no statistically significant differences in responder
rates and relative risk between MPGE and the comparator ESAs
(epoetin in Trial BA 16736 and darbepoetin in Trial BA16738).
In all trial comparisons the mean difference in the change in Hb
exceeded the non-inferiority margin of -0.75 g/dL.
There was no difference between MPGE and control ESA in the need
for transfusion in the trials. In the correction trials there was
slower time-to-target haemoglobin with MPGE (57 days vs 31 days in
Trial BA16736; and 43 days vs 29 days in Trial 16738, both
p<0.0001, using the log rank test).
The toxicity profiles of MPGE and the comparator ESAs were
generally similar. However, it was also noted that MPGE may be
associated with more serious gastro-intestinal bleeds, as there was
an excess of serious gastrointestinal haemorrhage events with MPGE
(21/1789 vs 2/948).
For PBAC’s view see Recommendation and
Reasons.
9. Clinical Claim
The submission described MPGE as non-inferior in terms of
comparative effectiveness and non-inferior in terms of comparative
safety over marketed erythropoietin stimulating agents.
For PBAC’s view see Recommendation and
Reasons.
10. Economic Analysis
The submission presented a cost minimisation analysis.
Equi-effective doses were presented separately using darbepoetin as
comparator and using epoetin as comparator and were derived from
the clinical trial data.
Where data were derived from more than one trial, estimates were
weighted by trial size.
For PBAC’s view see Recommendation and Reasons.
11. Estimated PBS Usage and Financial Implications
The likely number of patients per year accounting for market share
was estimated to be 10,000 – 50,000 in Year 5.
The net financial cost per year to the PBS was estimated to be zero
based on the assumption that MPGE is substituted for existing ESAs
and a market share approach is used to allocate prices based on
equi-effective doses.
12. Recommendation and Reasons
The PBAC recommended the listing of methoxy-polyethylene
glycol-epoetin beta (MPGE) under Section 100 (Highly Specialised
Drugs Program) for treatment of anaemia requiring transfusion,
defined as a haemoglobin level of less than 100 g per litre, where
intrinsic renal disease, as assessed by a nephrologist, is the
primary cause of anaemia, on a cost minimisation basis compared
with darbepoetin alfa and epoetin.
The calculation of equi-effective doses depends on the clinical
setting (correction vs maintenance) and route of administration.
The PBAC considered that there is substantial uncertainty in these
estimations of equi-effective doses as they differ depending on the
setting (correction versus maintenance), the comparator used, and
the trials used. These trial data give rise to dose relativities
for darbepoetin and epoetin that are different from those
previously accepted by the PBAC. The PBAC recommended that the cost
per day for the Erythropoeisis Stimulating Agents (ESAs) should be
the same, taking into account the different settings of use.
The PBAC noted that, because there is less frequent dosing with
MPGE, it takes longer to achieve target haemoglobin level (longer
half-life enables once-monthly dosing regimen) which was not
regarded as a clinically important difference. Patients treated
with MPGE may need to take more iron supplements (greater incidence
of relative iron deficiency for MPGE treated patients compared to
other ESAs; although in this clinical context almost all patients
are on iron supplementation. It was also noted that MPGE may be
associated with more serious gastro-intestinal bleeds.
Recommendation:
METHOXY-POLYETHYLENE GLYCOL-EPOETIN BETA, solution for injection,
30 micrograms in 0.3 mL, 50 micrograms in 0.3 mL, 75 micrograms in
0.3 mL, 100 micrograms in 0.3 mL, 120 micrograms in 0.3 mL, 200
micrograms in 0.3 mL and 360 micrograms in 0.6 mL, single use
pre-filled syringe
Restriction: Section 100 (Highly Specialised Drugs Program)
Private hospital authority required
Treatment of anaemia requiring transfusion, defined as a haemoglobin level of less than 100 g per L, where intrinsic renal disease, as assessed by a nephrologist, is the primary cause of the anaemia.
Pack size: 1
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 has no further comment.
