EPOETIN LAMBDA, injection, 1,000 units in 0.5 mL, 2,000 units in 1.0 mL, 3,000 units in 0.3 mL, 4,000 units in 0.4mL, 5,000 units in 0.5mL, 6,000 units in 0.6 mL, 8,000 units in 0.8 mL and 10,000 units in 1.0 mL, pre-filled syringe, Novicrit®
Page last updated: 20 October 2010
Public Summary Document
Product: EPOETIN LAMBDA, injection, 1,000 units in
0.5 mL, 2,000 units in 1.0 mL, 3,000 units in 0.3 mL, 4,000 units
in 0.4 mL, 5,000 units in 0.5mL, 6,000 units in 0.6 mL, 8,000 units
in 0.8 mL and 10,000 units in 1.0 mL, pre-filled syringe,
Novicrit®
Sponsor: Novartis Pharmaceuticals Australia Pty
Ltd
Date of PBAC Consideration: July 2010
1. Purpose of Application
The submission sought 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 L, 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
Epoetin lambda (Novicrit®) was TGA registered on 27 January 2010 for:
- treatment of patients with symptomatic or transfusion requiring anaemia associated with chronic renal failure to improve their quality of life by improving energy levels, exercise performance, fatigue and sleep patterns and by reducing the need for blood transfusions.
- treatment of anaemia in patients with non-myeloid malignancies where anaemia develops as a result of concomitantly administered chemotherapy, and where blood transfusion is not considered appropriate.
- adult patients with mild to moderate anaemia (haemoglobin > 100 to less than or equal to 130g/L) scheduled for elective surgery with an expected moderate blood loss (two to four units or 900 to 1,800mL) to reduce exposure to allogeneic blood transfusion and to facilitate erythropoietic recovery.
- augment autologous blood collection and to limit the decline in haemoglobin in anaemic adult patients who are scheduled for major elective surgery and who are not expected to pre-deposit their complete perioperative blood needs.
4. Listing Requested and PBAC’s View
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, 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.
Epoetin lambda would provide an alternative treatment for anaemia
associated with CKD.
6. Comparator
The submission nominated epoetin alfa as the comparator. The PBAC
considered this appropriate.
7. Clinical Trials
The submission presented the results of Study INJ-9 as the basis of
the evidence in support of listing. Details of the published trial
presented in the submission are in the table below.
| Trial ID / First Author | Protocol title / Publication title | Publication citation |
| Study INJ-9 Haag-Weber M, et al | Therapeutic equivalence, long-term efficacy and safety of HX575 in the treatment of anaemia in chronic renal failure patients receiving hemodialysis. | Clin Nephrol 2009; 72(5):380-90 |
8. Results of Trials
Study INJ-9 evaluated the therapeutic equivalence of epoetin lambda with epoetin alfa
in the long-term intravenous treatment of anaemia in chronic renal failure patients on haemodialysis only.
The primary efficacy outcome was mean absolute change in Hb level between the screening/baseline
period and the evaluation period. Major secondary efficacy outcomes were:
- Percentage of patients with Hb within the target range of 10.0 – 13.0 g/dL;
- Frequency of patients with Hb values > 10.0 g/dL;
- Frequency of patients with changes in the epoetin dosage (adaptation of more than 25% at any visit);
- Development of the weekly epoetin dose (in IU and per kg);
- Frequency of responders (PP)% (95% CI); and
- Red blood cell transfusions.
For the primary endpoint, the difference between treatment groups of 0.084 g/dL (95%
CI [-0.170; 0.338]) was within the pre-defined boundaries of -0.5 and 0.5 g/dL, therefore
meeting the criteria to confirm, with statistical significance, therapeutic non-inferiority
of epoetin lambda and epoetin alfa.
Regarding safety, the submission stated that no relevant differences between treatment
groups, with regard to adverse events, serious adverse events and death were observed.
The submission claimed that Study INJ-9 showed epoetin lambda to be therapeutically
non-inferior to epoetin alfa with respect to mean absolute change in Hb levels, and
to have a comparable safety profile in the IV treatment of anaemia in patients with
chronic kidney disease.
For PBAC’s view, see Recommendation and Reasons.
9. Clinical Claim
The submission claimed that epoetin lambda is non-inferior in terms
of efficacy and safety to epoetin alfa.
For PBAC’s view, see Recommendation and
Reasons.
10. Economic Analysis
The submission presented a cost-minimisation analysis. The
equi-effective doses were 1000 IU epoetin lambda and 1000 IU
epoetin alfa. The sponsor adopted a modified cost-minimisation
approach where epoetin lambda was provided at a 10% lower price
(ex-manufacturer) than the calculated equivalent price of the
calculated equivalent dose of epoetin alfa.
11. Estimated PBS Usage and Financial Implications
The submission used a market share approach to estimate the
financial impact of the requested listing for epoetin lambda.
Anticipated utilisation of epoetin lambda was calculated based on
substitution from the ESAs listed at the time of the submission
(epoetin alfa, epoetin beta and darbepoetin alfa) and assumed that
50% of total current ESA usage is by intravenous
administration.
The likely number of packs dispensed per year was estimated to be
between 10,000 and 50,000 in Year 5.
The submission estimated net savings to the PBS of less than $10
million in Year 5 of listing.
12. Recommendation and Reasons
The PBAC recommended the listing of epoetin lambda on the
Pharmaceutical Benefits Scheme as a Section 100 Highly Specialised
Drug for the treatment of anaemia requiring transfusion defined as
a haemoglobin level of less than 100 g per L, where intrinsic renal
disease, assessed by a nephrologist, is the primary cause of the
anaemia. Listing was recommended on a cost-minimisation basis with
epoetin alfa at the prices proposed in the submission, which the
PBAC noted are 10% lower than the current PBS price for the
corresponding strengths of epoetin alfa.
In making this recommendation, the PBAC noted that epoetin lambda
had been approved by TGA under the Similar Biological Medicinal
Product guidelines. When approving this product, the TGA had
concluded although the amino acid sequence of epoetin lambda was
the same as that of epoetin alfa, there were significant
differences in the glycosylation pattern of this product and
epoetin alfa which made it appropriate for the former to have the
different Australian Biologic Name, epoetin lambda.
The PBAC was satisfied that the results of Study INJ-9 demonstrate
that epoetin lambda is non-inferior to epoetin alfa in terms of
efficacy and safety when used at the same doses for the long-term
intravenous treatment of anaemia in chronic renal failure.
The PBAC agreed to advise the Minister and the Pricing Authority
that it is appropriate to apply the same price reduction offered in
this submission to the other PBS-listed erythropoiesis stimulating
agents; epoetin-alfa, epoetin beta, darbepoetin and
methoxypolyethylene glycol-epoetin beta, all of which were
recommended for listing on a cost-minimisation basis with epoetin
alfa.
In accordance with Subsection 101 (3BA) of the National Health
Act 1953 the PBAC advised that on the basis of the material
available to it at this time, the Committee is of the opinion that
epoetin lambda should not be considered as interchangeable on an
individual patient basis with another drug or medicinal
preparation. This is because, according to the TGA approved Product
Information, epoetin lambda can only be administered intravenously,
whereas the other PBS-subsidised erythropoiesis stimulating agents
can be administered intravenously and subcutaneously, and the
subcutaneous route of administration accounts for a significant
proportion of use of the PBS-subsidised erythropoiesis stimulating
agents. This means that these drugs are not sufficiently similar in
their clinical use.
Recommendation
EPOETIN LAMBDA, injection, 1,000 units in 0.5 mL, 2,000 units in
1.0 mL, 3,000 units in 0.3 mL, 4,000 units in 0.4 mL, 5,000 units
in 0.5 mL, 6,000 units in 0.6 mL, 8,000 units in 0.8 mL and 10,000
units in 1.0 mL, pre-filled syringe
Restriction: Section 100 (Highly Specialised Drugs Program)
Authority Required (STREAMLINED)
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.
NOTE:
Epoetin lambda should only be administered by the intravenous route.
Maximum quantity: 12
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
Novartis Pharmaceuticals Australia welcomes the PBAC’s recommendation to make Novicrit® available to patients with anaemia requiring transfusion.
