Corifollitropin Alfa, solution for injection, 100 micrograms in 0.5 mL pre-filled syringe, 150 micrograms in 0.5 mL pre-filled syringe, Elonva® - July 2011
Page last updated: 28 October 2011
Public Summary Document
Product: Corifollitropin Alfa, solution for
injection, 100 micrograms in 0.5 mL pre-filled syringe, 150
micrograms in 0.5 mL pre-filled syringe,
Elonva®
Sponsor: Merck Sharp & Dohme (Australia) Pty
Ltd (as Schering-Plough Pty Ltd)
Date of PBAC Consideration: July 2011
1. Purpose of Application
The submission sought Section 100 IVF/GIFT Program listing for
patients who are receiving medical treatment as described in items
13200, 13201 or 13202 of the Medicare Benefits Schedule.
2. Background
At the November 2010 meeting, the PBAC rejected the application to list corifollitropin
on the basis of uncertainty about the claim that it is non-inferior in terms of comparative
effectiveness and safety to follitropin beta, and the uncertainty in the cost-minimisation
analysis resulting from this clinical uncertainty and from the pricing structure proposed
by the sponsor.
A copy of the Public Summary Document (PSD) from the November 2010 meeting is available.
3. Registration Status
Corifollitropin was TGA registered on 30 July 2010 for controlled
ovarian stimulation (COS) for the development of multiple follicles
and pregnancy in women undergoing in-vitro fertilisation
techniques.
4. Listing Requested and PBAC’s View
Section 100 IVF/GIFT Program
Patients who are receiving medical treatment as described in items
13200, 13201 or 13202 of the Medicare Benefits Schedule.
Note:
Supply of these items is through an accredited IVF/GIFT clinic. For
enquiries relating to the IVF/GIFT Program, medical practitioners
should contact Medicare Australia on 1800 700 270.
For PBAC’s view, see Recommendation and
Reasons.
5. Clinical Place for the Proposed Therapy
Several different protocols exist for controlled ovarian
stimulation for assisted reproductive techniques (ART) using
different combinations of drug treatments. During controlled
ovarian stimulation, recombinant follicle stimulating hormone
(rFSH) is administered to stimulate follicular development. rFSH
administration is initiated on stimulation day one, and on average
adequate follicular development is achieved by the ninth day of
treatment (range 6-18 days). Human chorionic gonadotrophin can then
be administered to induce final oocyte maturation.
The submission proposed that corifollitropin alfa would replace the
first seven daily doses of rFSH (follitropin alfa or beta),
providing a reduced injection burden.
6. Comparator
The submission nominated conventional rFSH as the comparator,
focusing on follitropin beta. This was previously accepted by the
PBAC.
7. Clinical Trials
The PBAC noted that the trial data presented in the resubmission
were unchanged from the previous submission. Publication details
have been reported previously in the November 2010 Public Summary
Document.
8. Results of Trials
The results of the trials have been previously reported in the
November 2010 Public Summary Document.
9. Clinical Claim
The submission claimed corifollitropin alfa was non-inferior in
terms of effectiveness and non-inferior in terms of safety compared
to follitropin beta. The PBAC accepted that corifollitropin alfa
was non-inferior to follitropin beta when restricting the PBS
patient population to those most likely to respond to
corifollitropin alfa and least likely to experience ovarian
hyperstimulation syndrome (OHSS).
10. Economic Analysis
The submission presented a cost minimisation analysis. The
equi-effective doses based on the key trials ENGAGE and ENSURE are
corifollitropin alfa 150 micrograms as a single dose over seven
days and follitropin beta 200 IU as daily doses over seven days for
patients weighing greater than 60 kg; and corifollitropin alfa 100
micrograms as a single dose over seven days and follitropin beta
150 IU as daily doses over seven days for patients weighing 60 kg
or less.
A different pricing structure was proposed and a price reduction
was offered compared to the November 2010 submission.
11. Estimated PBS Usage and Financial Implications
The submission estimated the likely number of corifollitropin
cycles to be between 10,000 and 50,000 in Year 5, with estimated
net savings to the PBS of less than $5 million in Year 5.
12. Recommendation and Reasons
The PBAC recommended the listing of corifollitropin alfa in the
Section 100 IVF/GIFT Program for patients who are receiving medical
treatment as described in items 13200, 13201 or 13202 of the
Medicare Benefits Schedule on a cost minimisation basis to
follitropin beta. The equi-effective doses based on the key trials
ENGAGE and ENSURE are corifollitropin alfa 150 micrograms as a
single dose over seven days and follitropin beta 200 IU as daily
doses over seven days for patients weighing greater than 60 kg; and
corifollitropin alfa 100 micrograms as a single dose over seven
days and follitropin beta 150 IU as daily doses over seven days for
patients weighing 60 kg or less.
The PBAC noted the clinical evidence from the key trials, ENGAGE
and ENSURE, was unchanged in the re-submission. However, the
re-submission presented additional toxicity data on the incidence
and severity of ovarian hyperstimulation syndrome (OHSS) across
three trials, ENGAGE, ENSURE and TRUST, including the incidence of
early and late OHSS. The PBAC previously agreed that the
submission’s claim that corifollitropin alfa is non-inferior
in terms of comparative effectiveness and safety to follitropin
beta appeared reasonable only in women who are most likely to
respond well and least likely to “hyper-respond” (i.e.
to experience OHSS), and considered that the adverse event of most
concern for corifollitropin alfa was OHSS. The PBAC considered that
the additional toxicity data provided in the re-submission did not
resolve the uncertainty around the risk of OHSS. However, the PBAC
noted the sponsor’s request in its pre-PBAC response to
restrict the listing of corifollitropin alfa to aid in appropriate
patient selection and minimise the risk of OHSS by excluding:
- patients with an antral follicle count of greater than 20, as patients with an antral follicle count of greater than 20 were excluded from the trials;
- patients weighing more than 90 kg, as patients weighing over 90 kg were excluded from the ENGAGE trial; and
- patients receiving agonist cycles, as both ENSURE and ENGAGE investigated use of corifollitropin alfa in antagonist cycles only.
The PBAC recommended restricting the listing of corifollitropin
alfa in this way, accepting that this would assist in appropriate
patient selection.
The PBAC further noted and accepted the price reduction offered
compared to the submission to the November 2010 PBAC meeting. The
PBAC considered that the price reduction offered assisted in
reducing the uncertainty surrounding the comparative safety of
corifollitropin alfa compared to follitropin beta.
In summary, the PBAC accepted that corifollitropin alfa was
non-inferior to follitropin beta when restricting the PBS patient
population to those most likely to respond to corifollitropin alfa
and least likely to experience OHSS.
The PBAC acknowledged and noted the consumer comments received in
its consideration of corifollitropin alfa.
The PBAC recommended that corifollitropin alfa is not suitable for
inclusion in the PBS medicines for prescribing by nurse
practitioners.
Recommendation: CORIFOLLITROPIN ALFA
(rch), solution for injection, 100 micrograms in 0.5 mL pre-filled
syringe, 150 micrograms in 0.5 mL pre-filled syringe
Restriction:
Section 100 IVF/GIFT Program
A patient who is receiving medical treatment as described in items 13200, 13201 or 13202 of the Medicare Benefits Schedule and who:
- Has an antral follicle count of 20 or less; and
- Weighs 90 kg or less; and
- Is undergoing a gonadotropin releasing hormone antagonist cycle.
Note
Supply of these items is through an accredited IVF/GIFT clinic. For enquiries relating to the IVF/GIFT Program, medical practitioners should contact Medicare Australia on 1800 700 270.
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 is pleased that the PBAC’s decision will provide
a less-burdensome treatment alternative for patients who are
undergoing controlled ovarian stimulation.
