Proposal to fund aflibercept and rivaroxaban

Medicines

Consultation Closed

PHARMAC is seeking feedback on a proposal to list aflibercept (Eylea) and rivaroxaban (Xarelto) through a provisional agreement with Bayer New Zealand Limited.

What we’re proposing

We are also seeking feedback on a proposal to amend the current hospital restrictions for ranibizumab.

This proposal takes into account feedback received from a previous consultation  issued in September 2016 on a request for proposals (RFP) for anti-VEGF agents, and PHARMAC’s subsequent December 2016 decision to terminate the RFP process.

We are proposing to list (click on the link to take you to the detail):

  • aflibercept (Eylea) 40 mg per ml, 0.1 ml vials, from 1 June 2018, in Section B and in Part II of Section H of the Pharmaceutical Schedule, with restrictions;
  • rivaroxaban (Xarelto) 10 mg, 15 mg, and 20 mg tablets, from 1 August 2018, in Section B and in Part II of Section H of the Pharmaceutical Schedule, without restrictions (open list).

We are proposing to amend:

  • the current restrictions for ranibizumab (Lucentis) in Section H of the Pharmaceutical Schedule from 1 June 2018, to align them with updated clinical advice.

This consultation document is presented in two sections:

PHARMAC welcomes feedback on this proposal. To provide feedback, please submit it in writing by 5pm on Monday, 16 April 2018 to:

Tony Wang
Therapeutic Group Manager
PHARMAC

Email: consult@pharmac.govt.nz

Please share this information with other groups you think may be interested in providing feedback.

About aflibercept (Eylea)

Aflibercept is an anti-vascular endothelial growth factor (anti-VEGF) agent approved by Medsafe for the treatment of a range of ophthalmic conditions, including wet age related macular degeneration (wAMD) and diabetic macular oedema (DMO). For more information, see the Medsafe datasheet(external link).

What would the effect of listing aflibercept be?

For patients

From 1 June 2018, eligible patients with a range of ophthalmic conditions, including wet age-related macular degeneration (wAMD) and diabetic macular oedema (DMO), who meet the funding criteria would be eligible to receive funded access to aflibercept - a newer generation anti-VEGF treatment to preserve and improve vision.

If you meet the funding criteria for aflibercept, your ophthalmologist would be able to prescribe you this medicine and it would be dispensed by a community or hospital pharmacy on presentation of a prescription.

In some cases you might need to collect it from the pharmacy prior to the administration date and take it with you to your appointment, in other cases the health service would arrange this. Please note that this medicine must be stored in the fridge, and must not be frozen.

If the medicine is dispensed from a community pharmacy, the standard $5 or $15 pharmaceutical co-payment (depending on whether the medicine is prescribed by a DHB Hospital ophthalmologist or a private ophthalmologist) would apply.

Patients who are currently receiving treatment with ranibizumab would have the option to switch to aflibercept. Please discuss with your ophthalmologist whether aflibercept might be the right treatment option for you.

For ophthalmologists

This proposal would mean that from 1 June 2018, you would be able to prescribe fully funded aflibercept for eligible patients who meet funding criteria for the treatment of a range of ophthalmic conditions, including wAMD and DMO.

To access treatment funded via the Combined Pharmaceutical Budget you would need to apply for a Special Authority (SA) approval in advance of treating your patient; these can be applied for electronically or manually and the approval number must be printed on the prescription.

Pharmacies would be able to dispense funded aflibercept on presentation of a prescription with a valid SA approval number. You might ask patients to collect the medicine from the pharmacy and bring it with them to the administration appointment, or you might arrange for the collection of the product on patients’ behalf. Please note that this medicine must be stored in the fridge between 2o and 8oC, and must not be frozen. Aflibercept can be stored at or below 25oC for up to 24 hours.

Under the proposed funding criteria, prior to 1 January 2019, patients who are currently receiving funded treatment with ranibizumab would have the option to switch to using aflibercept. If you consider a patient would benefit from aflibercept, you would be able to apply for an initial Special Authority approval for them under proposed criterion 2.2. Note that this criterion would be removed from 1 January 2019.

After 1 January 2019, if your patient has been receiving funded treatment with ranibizumab for longer than 3 months, they would no longer be eligible for funded aflibercept. Similarly, patients who have received funded treatment with aflibercept for longer than 3 months would no longer be eligible for funded ranibizumab. These restrictions are in keeping with advice from PHARMAC’s clinical advisory committee which recommended that funding for the use of anti-VEGF agents in the 3rd line setting be declined.

Note that patients who experience intolerance to aflibercept or ranibizumab within the first 3 months of use would remain eligible to change to an alternative 2nd line anti-VEGF agent, even after 1 January 2019.

For community and hospital pharmacies

The proposal is to list aflibercept vials in both Section B and Part II of Section H of the Pharmaceutical Schedule from 1 June 2018. This means that patients with a Special Authority approval could bring a prescription from their ophthalmologist to a community pharmacy (or have it faxed through) to access funded aflibercept, or that reimbursement claims could be made (electronically or manually) by hospital pharmacies with a community pharmacy contract claimant number.

Aflibercept is presented in a sealed original pack containing one vial and a filter needle. Aflibercept must be stored in the fridge between 2º and 8ºC, and must not be frozen. Aflibercept can be stored at or below 25 ºC for up to 24 hours.

For DHB hospitals

The proposal would enable aflibercept to be funded from 1 June 2018, for use in both in the hospital and community settings.

It is anticipated that this proposal may help to address some of the capacity issues in DHB ophthalmology services. This is because, for some conditions, the frequency of dosing using aflibercept may be less than that with currently listed anti-VEGF agents (i.e, longer time in between injections).

Under the proposal, funded aflibercept would also be available for patients being treated in the community by private ophthalmologists or other qualified clinicians, which may further shift demand from DHB hospitals.

Why we’re proposing to list aflibercept

Patients with wAMD are currently able to access bevacizumab (off-label) and ranibizumab injections for the preservation of vision. Patients with DMO currently only have access to bevacizumab (off-label) injections. The current Pharmaceutical Schedule listing restrictions for both bevacizumab and ranibizumab only enable publicly funded access when used in the DHB hospital setting.

Aflibercept (EYLEA) is a recombinant fusion protein that competes for binding of vascular endothelial growth factor-A (VEGF-A) and placental growth factor (P1GF), and is a newer generation anti-VEGF agent used for the treatment for wAMD and DMO.

This proposal is to list aflibercept in Section B and Section H of the Pharmaceutical Schedule as the 2nd line anti-VEGF agent for both community and hospital use.

There would be no change to the current listing of bevacizumab as a result of this proposal.

About wet age-related macular degeneration (wAMD)

Age-related Macular Degeneration (AMD) is the most common cause of blindness and it affects 1 in 7 people over the age of 50. The incidence of AMD increases with age; it is estimated by the age of 80, one in four New Zealanders have vision loss from AMD. There are two forms of AMD, wet and dry. Wet (neovascular) AMD affects 85-90% of patients with AMD and is a degenerative disease of the central portion of the retina (the macula) that results primarily in loss of central vision.

Anti-VEGF agents are considered to be the standard treatment for wet AMD. They are intravitreal injections which are administered into the eye, usually by an ophthalmologist or other qualified health professionals.

About diabetic Macular Oedema (DMO)

Diabetic Macular Oedema (DMO) is a serious complication of type 1 and 2 diabetes. It is associated with poor diabetic control and is the leading cause of blindness in people with diabetes.

DMO disproportionately affects Maori and Pacific populations as the rates for diabetes are two to three times higher in these populations compared with Europeans, as are the rates of uncontrolled diabetes.

Clinical advice

Wet age-related macular denegeration (wAMD)

In May 2016, PHARMAC released a Request for Proposals for the supply of anti-VEGF agents for the treatment of wAMD. In September 2016 we consulted on a proposal to list ranibizumab (Lucentis) and aflibercept (Eylea) the second and third line treatment (respectively) of wet age-related macular degeneration (wAMD). After carefully considering feedback received, in December 2016 we announced our decision not to accept any proposal and to terminate the RFP process.

Consultation feedback included a strong preference from some clinicians for aflibercept to be the second line treatment listed for wAMD, rather than ranibizumab as had been proposed. Some responders included evidence to support their views that PHARMAC had not previously considered.

PHARMAC then sought additional clinical advice from our Pharmacology and Therapeutics Advisory Committee (PTAC) on the issues raised in feedback.

In May 2017, PTAC recommended that aflibercept be funded as second line anti-VEGF agent after bevacizumab, with a medium priority. The Committee also recommended that access criteria for second line aflibercept be referred to the Ophthalmology Subcommittee for further development, including the inclusion of objective entry and exit criteria. Minutes of the May 2017 PTAC meeting are available here [PDF, 534 KB].

In September 2017, the Ophthalmology Subcommittee recommended criteria for second line anti-VEGF treatment for wAMD, with objective entry and exit criteria. Minutes of that meeting can be found here. [PDF, 380 KB]

In November 2017, PTAC considered the minutes of the Ophthalmology Subcommittee meeting. PTAC considered that if aflibercept were to be listed alongside ranibizumab, that there should be a time limited restriction to allow those patients who are currently using ranibizumab to switch to aflibercept (as continuation of second line anti-VEGF treatment). Minutes of that meeting can be found here [PDF, 764 KB].

Diabetic macular oedema (DMO)

In February 2016, the Ophthalmology Subcommittee reviewed the evidence for aflibercept for the treatment of diabetic macular oedema (DMO). The Subcommittee recommended that aflibercept be funded as the second line anti-VEGF agent with a high priority. Minutes of the February 2016 Ophthalmology Subcommittee meeting are available here [PDF, 99 KB].

At its meeting in May 2016, PTAC accepted the minutes of the February 2016 Ophthalmology Subcommittee meeting. Minutes are available here [PDF, 1.2 MB].

In May 2017, PTAC reviewed the evidence for second line anti-VEGF agents for the treatment of DMO. PTAC again discussed aflibercept as the second line agent for the treatment of diabetic macular oedema (DMO). The Committee recommended that access criteria for a second line anti-VEGF treatment be referred to the Ophthalmology Subcommittee for further development, including the inclusion of objective entry and exit criteria. Minutes of the May 2017 PTAC meeting are available here [PDF, 534 KB].

In September 2017, the Ophthalmology Subcommittee recommended criteria for second line anti-VEGF treatment for DMO, with objective entry and exit criteria. Minutes of that meeting can be found here [PDF, 380 KB].

In November 2017, PTAC considered the minutes of the Ophthalmology Subcommittee meeting. Minutes of that meeting can be found here. [PDF, 764 KB]

Who we think will be interested

  • Patients with ophthalmic conditions (such as wet age related macular degeneration, polypoidal choroidal vasculopathy, choroidal neovascular membrane, diabetic macular oedema)
  • Public and private ophthalmologists
  • Public ophthalmology departments and private ophthalmology clinics
  • Community and hospital pharmacies and pharmacists
  • Suppliers and wholesalers
  • Ministry of Health

Details about the aflibercept proposal

PHARMAC is seeking feedback on a proposal to list aflibercept 40 mg per ml, 0.1 ml vials from 1 June 2018, subject to restrictions, in Section B and Part II of Section H of the Pharmaceutical Schedule, at the following price and subsidy (ex-manufacturer, excluding GST): 

Chemical Presentation Brand Pack size Price and subsidy
Aflibercept 40 mg per ml, 0.1 ml vial Eylea 1 $1,250.00

A confidential rebate would apply which would reduce the net price to the Funder.

It is proposed that aflibercept be listed in Section B subject to the following Special Authority criteria:

Special Authority for Subsidy

Initial application – (wet age related macular degeneration) only from an ophthalmologist.  Approvals valid for 3 months for applications meeting the following criteria: 

Either:

NOTE: Criterion 2.2 will be removed from 1 January 2019.

Renewal – (wet age related macular degeneration) only from an ophthalmologist. Approvals valid for 12 months for applications meeting the following criteria:

All of the following:

  1. Documented benefit must be demonstrated to continue; and
  2. Patient’s vision is 6/36 or better on the Snellen visual acuity score; and
  3. There is no structural damage to the central fovea of the treated eye.

Initial application – (diabetic macular oedema) only from an ophthalmologist.  Approvals valid for 4 months for applications meeting the following criteria: 

All of the following:

  1. Patient has centre involving diabetic macular oedema (DMO); and
  2. Patient’s disease is non responsive to 4 doses of intravitreal bevacizumab when administered 4-6 weekly; and
  3. Patient has reduced visual acuity between 6/9 – 6/36 with functional awareness of reduction in vision; and
  4. Patient has DMO within central OCT (ocular coherence tomography) subfield >350 micrometers; and
  5. There is no centre-involving sub-retinal fibrosis or foveal atrophy.

Renewal – (diabetic macular oedema) only from an ophthalmologist.  Approvals valid for 12 months for applications meeting the following criteria: 

All of the following:

  1. There is stability or two lines of Snellen visual acuity gain; and
  2. There is structural improvement on OCT scan (with reduction in intra-retinal cysts, central retinal thickness, and sub-retinal fluid); and
  3. Patient’s vision is 6/36 or better on the Snellen visual acuity score; and
  4. There is no centre-involving sub-retinal fibrosis or foveal atrophy; and
  5. After each consecutive 12 months treatment with [2nd line anti-VEGF agent], patient has retrialled with at least one injection of bevacizumab and had no response.

It is proposed that aflibercept be listed in Part II of Section H subject to the following restrictions:

Restricted

Initiation – Wet Age Related Macular Degeneration

Ophthalmologist

Reassessment required after 3 months

Either:

NOTE: Criterion 2.2 will be removed from 1 January 2019.

Continuation - Wet Age Related Macular Degeneration

Ophthalmologist

Re-assessment required after 12 months

All of the following:

  1. Documented benefit must be demonstrated to continue; and
  2. Patient’s vision is 6/36 or better on the Snellen visual acuity score; and
  3. There is no structural damage to the central fovea of the treated eye.

Initiation – Diabetic Macular Oedema

Ophthalmologist

Re-assessment required after 4 months

All of the following:

  1. Patient has centre involving diabetic macular oedema (DMO); and
  2. Patient’s disease is non responsive to 4 doses of intravitreal bevacizumab when administered 4-6 weekly; and
  3. Patient has reduced visual acuity between 6/9 – 6/36 with functional awareness of reduction in vision; and
  4. Patient has DMO within central OCT (ocular coherence tomography) subfield >350 micrometers; and
  5. There is no centre-involving sub-retinal fibrosis or foveal atrophy.

Continuation - Diabetic Macular Oedema

Ophthalmologist

Re-assessment required after 12 months

All of the following:

  1. There is stability or two lines of Snellen visual acuity gain; and
  2. There is structural improvement on OCT scan (with reduction in intra-retinal cysts, central retinal thickness, and sub-retinal fluid); and
  3. Patient’s vision is 6/36 or better on the Snellen visual acuity score; and
  4. There is no centre-involving sub-retinal fibrosis or foveal atrophy; and
  5. After each consecutive 12 months treatment with aflibercept, patient has retrialled with at least one injection of bevacizumab and had no response.

It is also proposed that the restrictions for ranibizumab be amended in Part II of Section H from 1 June 2018 to reflect the criteria as recommended by the Ophthalmology Subcommittee for treatment of wAMD. Please note that ranibizumab would remain listed for use only in DHB hospitals for the treatment of wAMD (additions in bold, deletions in strikethrough):

Initiation

Re-assessment required after 3 doses

Continuation

Both:

1     Documented benefit after three doses must be demonstrated to continue; and
2     In the case of previous non-response to bevacizumab, a retrial of bevacizumab is required to confirm non-response before continuing with ranibizumab

Initiation – Wet Age Related Macular Degeneration

Ophthalmologist

Reassessment required after 3 months

Either:

Continuation

Ophthalmologist

Re-assessment required after 12 months

All of the following:

The proposed criteria for both aflibercept and ranibizumab are in keeping with the clinical advice and recommendations received from the Ophthalmology Subcommittee and PTAC.

About rivaroxaban (Xarelto)

Rivaroxaban is an oral anticoagulant (direct factor Xa inhibitor) approved by Medsafe for the prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation and the treatment and prevention of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE). For more information, see the Medsafe datasheet(external link).

Anticoagulants reduce the tendency of the blood to form clots.

What would the effect of listing rivaroxaban be?

For patients

The listing of rivaroxaban would mean that, from 1 August 2018, patients for whom it is deemed clinically appropriate would be able to access fully funded rivaroxaban tablets from their community pharmacies with a prescription, regardless of the reason they require an anticoagulant.

For clinicians

The effect of this proposal would mean that from 1 August 2018, prescribers would be able to prescribe funded rivaroxaban tablets for any of their patients whom they consider clinically appropriate to receive treatment with it. The Special Authority criteria, that currently limit the use of rivaroxaban for prophylaxis of venous thromboembolism following a total hip or knee replacements, would be removed.  The effect of this would be that rivaroxaban would be ‘open listed’ and no Special Authority approvals would be required to access funded treatment.

Rivaroxaban may be particularly useful for those patients who are unable to take dabigatran or warfarin.

For community and hospital pharmacies

The proposal is to list rivaroxaban from 1 August 2018. This means that rivaroxaban could be used in DHB hospitals for any indication and patients could bring a prescription to a community pharmacy to access funded rivaroxaban.

The Special Authority restrictions that currently limit the use of rivaroxaban for prophylaxis of venous thromboembolism following a total hip or knee replacements would be removed. 

Who we think will be interested

  • Cardiologists, haematologists, surgeons, specialist nurses, general practitioners, and any other clinician prescribing or involved in the care of patients taking anticoagulants  
  • Community and hospital pharmacies and pharmacists
  • Suppliers and wholesalers
  • Some of the patients who require anticoagulants to prevent or treat blood clots (depending on the condition being treated). This may include some patients for whom dabigatran and warfarin not appropriate, not tolerated or who experience difficulties with dose management.

Why we’re proposing to list rivaroxaban 

Atrial fibrillation (AF) is a disorder of abnormal heart rhythm (arrhythmia) involving the two upper chambers (atria) of the heart, which lead to the heart working less efficiently. Anticoagulation forms a key part of treatment in AF as the condition increases the risk of blood clots, which is a risk for strokes or systemic embolisms.

Deep vein thromboses and pulmonary embolisms are commonly referred to as venous thromboembolic (VTE) events. VTE is a condition in which a blood clot (thrombus) forms in a vein. If a part of the blood clot in the vein breaks off from the site where it was created, it can travel through the blood until it reaches a narrower point, and forms a blockage called an embolus. A pulmonary embolus (PE) is an embolus which has lodged in the lung and it is a serious condition which can result in death.

Two oral anticoagulants are currently funded for the treatment of AF and VTE: warfarin and dabigatran.

Warfarin requires close monitoring with frequent blood tests to maintain it within a therapeutic range and to minimise adverse effects like bleeding. Dabigatran (and rivaroxaban) is a newer class of anticoagulant sometimes called Novel Oral Anticoagulants (NOACs) or Direct Oral Anticoagulants (DOACs). NOACs/DOACs are often more convenient to use than warfarin, however, a number of patients are unable to take them (including those with prosthetic heart valves).

Dabigatran has been funded in New Zealand since July 2011, although some patients are not able to take dabigatran because intolerance or contraindications, particularly gastrointestinal intolerance and moderate-severe renal impairment. Rivaroxaban may be able to be used as an alternative, and is dosed once-daily in the majority of patients.

Clinical advice

In May 2014, following consideration by the Cardiovascular, Haematology and Neurological Subcommittees, PTAC recommended rivaroxaban be funded for stroke prevention in atrial fibrillation and the treatment and prevention of venous thromboembolism only if cost neutral to dabigatran. The minutes of those meetings can be accessed here and here.

More recently, in September and October 2017, the Cardiovascular [PDF, 178 KB] and Haematology [PDF, 317 KB] Subcommittees discussed the funding of NOACs/DOACs in New Zealand. They both considered there is an unmet clinical need in the patient group who are not able to take dabigatran, estimating this would be around 15% of dabigatran-treated patients. The Cardiovascular and Haematology Subcommittees considered that it would be desirable to have one additional NOAC listed on the Pharmaceutical Schedule and recommended another NOAC was funded with high and medium priorities respectively.

Details about the rivaroxaban proposal

PHARMAC is seeking feedback on a proposal to list rivaroxaban tablets 10 mg, 15 mg and 20 mg, and reduce the price/subsidy for tab 10 mg 15 tab pack, from 1 August 2018 in Section B and Part II of Section H of the Pharmaceutical Schedule, at the following prices and subsidies (ex-manufacturer, excluding GST):

Chemical

Presentation

Brand

Pack size

Current price and subsidy

Proposed price and subsidy

Rivaroxaban

Tab 10 mg

XARELTO

15

$153.00

$41.55

Rivaroxaban

Tab 10 mg

XARELTO

30

-

$83.10

Rivaroxaban

Tab 15 mg

XARELTO

28

-

$77.56

Rivaroxaban

Tab 20 mg

XARELTO

28

-

$77.56

A confidential rebate would apply to rivaroxaban which would reduce the net price to the Funder.

It is proposed that rivaroxaban be listed in Section B and Part II of Section H without restrictions, except for a rule in Section B limiting the use of the 10 mg presentation to one tablet per day.

The proposal to ‘open list’ rivaroxaban is in line with clinical advice received. Due to the commercial arrangements in place with the supplier, PHARMAC does not consider restrictions are required to manage expenditure on rivaroxaban.

To provide feedback

PHARMAC welcomes feedback on this proposal. To provide feedback, please submit it in writing by 5pm, Monday, 16 April 2018 to:

Tony Wang
Therapeutic Group Manager
PHARMAC
PO Box 10254
Wellington 6143

Email: consult@pharmac.govt.nz

Fax: 04 460 4995

Feedback we receive is subject to the Official Information Act 1982 (OIA) and we will consider any request to have information withheld in accordance with our obligations under the OIA. Anyone providing feedback, whether on their own account or on behalf of an organisation, and whether in a personal or professional capacity, should be aware that the content of their feedback and their identity may need to be disclosed in response to an OIA request.

We are not able to treat any part of your feedback as confidential unless you specifically request that we do, and then only to the extent permissible under the OIA and other relevant laws and requirements. If you would like us to withhold any commercially sensitive, confidential proprietary, or personal information included in your submission, please clearly state this in your submission and identify the relevant sections of your submission that you would like it withheld. PHARMAC will give due consideration to any such request.