Decision to widen access to pulmonary arterial hypertension treatments

Medicines Decision

We’re pleased to announce our decision to widen funded access to five treatments for pulmonary arterial hypertension (PAH). This decision takes effect from 1 February 2018. Amended 30 January 2018.

Amended - 30 January 2018

Our original notification stated that we would allow clinicians to ask general advice of the PAH panel outside of normal funding applications.

Following further advice, we consider this is not a tenable approach, and have removed this from the notification.

We encourage clinicians who wish to seek advice to contact PAH experts.

What we're doing

We’re pleased to announce our decision to widen funded access to five treatments for pulmonary arterial hypertension (PAH).

This decision will:

  • List epoprostenol (Veletri) in Section B of the Schedule (community access) and widen funded access for certain severe patients;
  • Reduce the severity requirement to include all patients who are NYHA Functional Class II;
  • Fund earlier dual therapy, by reducing the number of required monotherapy trials from two to one;
  • Fund triple therapy for patients with certain severe circumstances;
  • Allow clinicians to apply for sildenafil and bosentan funding through the standard Special Authority application process, instead of applying to the PAH Panel; and
  • Allow treating clinicians to seek expert clinical advice from the PAH Panel.

The decision takes effect from 1 February 2018.

If you have any questions about this decision, you can email us at enquiry@pharmac.govt.nz or call our toll free number (9 am to 5 pm, Monday to Friday) on 0800 66 00 50.

What has changed from our original proposal?

This was the subject of a consultation letter dated 15 November 2017.

The final decision differed from that consultation in the following ways:

  • applications for standard Special Authorities for sildenafil and bosentan have been limited to certain specialists;
  • duplicate criteria about being on the lung transplant list have been removed;
  • the required value for PCWP in the sildenafil Special Authority has been changed from 18 to 15 mmHg;
  • clarity on quadruple and quintuple therapy has been added.

About the products

Five treatments are currently funded for PAH: sildenafil, bosentan, ambrisentan, iloprost, and epoprostenol (epoprostenol has previously only been listed in Section H [DHB hospital]). These cover three different classes of treatment, and vary in dose form from oral tablets to continuous infusion.

Who we think will be most interested

People who may be interested in this decision might include patients with PAH, clinicians who treat PAH, and suppliers of PAH treatments.

What will the effect of this decision be?

For patients

Generally, new patients will be able to begin on a treatment for PAH sooner, and will be able to move to combination therapies sooner if monotherapy is not effective. For those with highly severe PAH, more treatment options will be available. Epoprostenol will be available for highly severe patients, as will triple therapy.

For prescribers

Prescribing the most common funded PAH treatments, sildenafil and bosentan, will now be simpler, as from 1 February 2018 these will no longer require applications to the PAH Panel.

Any treating clinicians who would like advice from this group of specialists in PAH can submit information about their cases to the PAH Panel to receive its advice on diagnosis and treatment.

Patients who have an existing Special Authority approval for sildenafil or bosentan through the Panel will have a new Special Authority number automatically generated for them.  At the end of January 2018, prescribers will be notified of the new Special Authority approval numbers which will need to be printed on prescriptions for their PAH patients who are currently using funded sildenafil or bosentan.

A further guide on how these changes will practically affect prescribing and funding of PAH treatments is available.

Detail about this decision

All changes will be made from 1 February 2018.

Expert advice

In addition to the changes to the Schedule which are detailed below, we are also offering to facilitate a process for any clinician wishing to obtain expert clinical advice from the PAH Panel.

As the Panel will no longer be reviewing the initial diagnoses of most patients, clinicians may wish to present a patient case to the PAH Panel to receive advice and opinions on diagnosis and treatment options. This is separate to applications for funding.

Clinicians would not be required to ask for this advice, or follow it, but can use this resource at their discretion.

Special Authority and Schedule listing changes

The Special Authority in Section B of the Schedule for sildenafil will be replaced with the following:

Special Authority for Subsidy

Initial application — (Raynaud’s Phenomenon from any relevant practitioner. Approvals valid without further renewal unless notified for applications meeting the following criteria:

All of the following:

  1. Patient has Raynaud’s Phenomenon*; and
  2. Patient has severe digital ischaemia (defined as severe pain requiring hospital admission or with a high likelihood of digital ulceration; digital ulcers; or gangrene); and
  3. Patient is following lifestyle management (avoidance of cold exposure, sufficient protection, smoking cessation support, avoidance of sympathomimetic drugs); and
  4. Patient is being treated with calcium channel blockers and nitrates (or these are contraindicated/not tolerated).

Initial application – (Pulmonary arterial hypertension*) only from a respiratory physician or cardiologist or medical practitioner on the recommendation of a respiratory physician or cardiologist. Approvals valid without further renewal unless notified for applications meeting the following criteria:

All of the following:

  1. Patient has pulmonary arterial hypertension (PAH)*; and
  2. Any of the following:
    1. PAH is in Group 1 of the WHO (Venice) clinical classifications; or
    2. PAH is in Group 4 of the WHO (Venice) clinical classifications, or
    3. PAH is in Group 5 of the WHO (Venice) clinical classifications; and
  3. Any of the following:
    1. PAH is in NYHA/WHO functional class II; or
    2. PAH is in NYHA/WHO functional class III; or
    3. PAH is in NYHA/WHO functional class IV; and
  4. Patient has a pulmonary capillary wedge pressure (PCWP) less than or equal to 15 mmHg; and
  5. Either:
    1. Patient has a mean pulmonary artery pressure (PAPm) > 25 mmHg; or
    2. Patient is peri Fontan repair; and
  6. Patient has a pulmonary vascular resistance (PVR) of at least 3 Wood Units or at least 240 International Units (dyn s cm-5).
Indications marked with * are Unapproved Indications.

The Special Authority in Section B of the Schedule for bosentan will be replaced with the following:

Special Authority for Subsidy

Initial application only from a respiratory physician or cardiologist or medical practitioner on the recommendation of a respiratory physician or cardiologist. Approvals valid for 6 months for applications meeting the following criteria:

All of the following:

  1. Patient has pulmonary arterial hypertension (PAH); and
  2. Any of the following:
    1. PAH is in Group 1 of the WHO (Venice) clinical classifications; or
    2. PAH is in Group 4 of the WHO (Venice) clinical classifications, or
    3. PAH is in Group 5 of the WHO (Venice) clinical classifications; and
  3. Any of the following:
    1. PAH is at NYHA/WHO functional class II; or
    2. PAH is at NYHA/WHO functional class III; or
    3. PAH is at NYHA/WHO functional class IV; and
  4. Any one of the following:
    1. Both:
      1. Bosentan is to be used as PAH monotherapy; and
      2. Either:
        1. Patient is intolerant or contraindicated to sildenafil; or
        2. Patient is a child with idiopathic PAH or PAH secondary to congenital heart disease; or
    2. Both:
      1. Bosentan is to be used as PAH dual therapy; and
      2. Either:
        1. Patient has tried a PAH monotherapy for at least three months and failed to respond, or
        2. Patient deteriorated while on a PAH monotherapy; or
    3. Both:
      1. Bosentan is to be used as PAH triple therapy; and
      2. Any of the following:
        1. Patient is on the lung transplant list; or
        2. Patient is presenting acutely with idiopathic pulmonary arterial hypertension (IPAH) in New York Heart Association/World Health Organization (NYHA/WHO) Functional Class IV; or
        3. Patient is deteriorating rapidly to NYHA/WHO Functional Class IV who may be lung transplant recipients in the future, if their disease is stabilised; or
        4. Patient has PAH associated with the scleroderma spectrum of diseases (APAHSSD) who have no major morbidities and are deteriorating despite combination therapy.

Renewal from a respiratory physician or cardiologist or medical practitioner on the recommendation of a respiratory physician or cardiologist. Approvals valid for 2 years for applications meeting the following criteria:

Any one of the following:

  1. Both:
    1. Bosentan is to be used as PAH monotherapy; and
    2. Patient is stable or has improved while on bosentan; or
  2. Both:
    1. Bosentan is to be used as PAH dual therapy; and
    2. Patient has tried a PAH monotherapy for at least three months and either failed to respond or later deteriorated; or
  3. Both:
    1. Bosentan is to be used as PAH triple therapy; and
    2. Any of the following:
      1. Patient is on the lung transplant list; or
      2. Patient is presenting acutely with idiopathic pulmonary arterial hypertension (IPAH) in New York Heart Association/World Health Organization (NYHA/WHO) Functional Class IV; or
      3. Patient is deteriorating rapidly to NYHA/WHO Functional Class IV who may be lung transplant recipients in the future, if their disease is stabilised; or
      4. Patient has PAH associated with the scleroderma spectrum of diseases (APAHSSD) who have no major morbidities and are deteriorating despite combination therapy.

Epoprostenol will be listed in Section B of the Schedule, with the following criteria:

Special Authority for Subsidy
Special Authority approved by the Pulmonary Arterial Hypertension Panel
Notes: Application details may be obtained from PHARMAC's website(external link) or:

The Coordinator, PAH Panel
PHARMAC, PO Box 10-254, WELLINGTON

Tel: (04) 916 7561, Fax: (04) 974 4858, Email: PAH@pharmac.govt.nz

The document which governs applications to the PAH Panel will be changed.

A copy of the document will be on PHARMAC’s website from 1 February 2018.

Changes will also be made to Section H from 1 February 2018. Apart from minor wording changes, the only functional change is to epoprostenol, as follows (additions in bold, deletions in strikethrough):

Restricted

Initiation

For use as a bridge to transplant for patients with Pulmonary Arterial Hypertension who are on the active waiting list for lung transplantation.

Either:

  1. For use in patients with a valid Special Authority approval for epoprostenol in pulmonary arterial hypertension; or
  2. In hospital stabilisation in emergency situations.

The description of the smaller vial size of epoprostenol will be changed from “0.5 mg vial” to “500 mcg vial”, to match the description in the Medsafe datasheet.

Our response to what you told us

We’re really grateful for the time people took to respond to this consultation. The table below summarises the main themes raised in feedback, any changes we have made in response to that feedback, and other responses to the feedback received.

Feedback theme

PHARMAC response

The PAH Panel should review patients when they would receive their first treatment, to prevent misdiagnosis and mistreatment.

Supports removal of requirement to complete PAH Panel applications, which take significant clinician time.

We acknowledge that diagnosing PAH can be difficult.

To assist clinicians in making accurate diagnoses, we will fund the operation of the PAH Panel to provide advice on diagnosis and treatment to clinicians to present that wish to use this resource.

We consider that clinicians already have access to expert advice to assist in the dignosis and treament of PAH.

PAH treatment should be restricted to a limited number of centres.

It is outside PHARMAC’s remit to restrict access to pharmaceuticals to specific treatment centres.

The criterion for PCWP in sildenafil should be 15 mmHg, not 18.

The PAH Panel should retain the power to consider applications for sildenafil or bosentan for patients with PCWP between 15 and 18 mmHg.

We changed this criterion following consideration on this feedback. 

International standards we reviewed were universal in their use of 15 mmHg for PCWP.  We would be happy to consider evidence that supports a change to 18 mmHg if that is provided to us.

Dual therapy should be available if monotherapy does not result in meeting treatment goals as per international practice.

PTAC have discussed goal-oriented therapy and did not recommended its use, based on poor evidence.

Reword the section on vasoreactivity testing, as it is only relevant to WHO class 1.1 PAH

Our research suggests there are other groups for which vasoreactivity testing is relevant. The criteria allow for the test to not be carried out, as long as reasons are given.

We would welcome a submission on changing this part of the Special Authority.

Bosentan should be funded without further renewal after meeting initial criteria.

Bosentan’s two year renewal period is too long and more regular reviews are required.

We consider that a renewal for bosentan is appropriate to ensure funding continues to be appropriate.

Clinical reviews can occur more frequently than the funding renewal periods.

More than one endothelin receptor antagonist (ERA) should be allowed as a first line.

The decision would mean that two ERAs (ambrisentan and bosentan), will be funded under similar criteria, although ambrisentan funding would require an application to the PAH panel.

PHARMAC should take the role of supporting best practice and encouraging use of guidelines.

PHARMAC will support best practice by enabling clinicians to present cases to the PAH Panel for advice, as described above.

We consider it the responsibility of the clinician to follow best practice.

First-line dual therapy, or even triple therapy should be funded.

Earlier combination therapy should be funded in sicker patients (eg FC III and FC IV).

We do not have PTAC advice on first-line combination therapy, in any group of patients, as we have not received any applications requesting this.

We would welcome funding applications for widening access to dual or triple therapy.

Selexipag and macitentan should be funded.

We have received funding applications for selexipag and macitentan and are assessing them. This decision does not prevent selexipag or macitentan being funded at a later date.

Riociguat should be funded for certain patients.

PHARMAC has not received a funding application for riociguat. We would welcome an application for this product.

This will require manual work by the Ministry of Health to move Panel approvals to normal Special Authority approvals. PHARMAC will need to supply written approval to confirm how to do the changes.

Noted. We are working with the Ministry to ensure the exiting Special Authority approvals are successfully transitioned.