Post-market Review of Pulmonary Arterial Hypertension (PAH) Medicines

Page last updated: 3 February 2023

Disclaimer

Every effort has been made to ensure web accessibility to the Post-market Review of Pulmonary Arterial Hypertension medicines, however complete web accessibility cannot be guaranteed. If you have trouble accessing information within the report and you would like a copy to be provided to you, please direct all queries via email to PBS postmarket.

Background

Pulmonary Arterial Hypertension (PAH) is a type of high blood pressure that arises when the arteries on the right side of the heart that supply blood to the lungs (pulmonary arteries) thicken and become rigid. When the pulmonary arteries thicken, the heart needs to work harder to provide adequate blood flow to the lungs, meaning that the body may not get all the oxygen it needs to function well. Patients with PAH can experience shortness of breath, dizziness, chest pain and fatigue.

A PAH diagnosis is confirmed by detection of high blood pressure in the pulmonary artery and the severity of disease is classified by its impact on physical activity. The PAH World Health Organization (WHO) Functional Class classification of symptoms is used to define the severity of disease as experienced by patients, as summarised in Table 1.

Table 1. Summary of PAH WHO Functional Class classification of symptoms
PAH WHO Functional Class*	Description of symptoms
1 ^(I)	No symptoms of PAH during physical activity or when at rest.
2 ^(II)	Symptoms occur during normal physical activity but not when at rest.
3 ^(III)	Symptoms occur during normal and minor physical activity but not when at rest.
4 ^(IV)	Symptoms occur with any physical activity and when at rest.

*Functional Class 1, 2, 3 and 4 is referred to in international guidelines, and also the PBS criteria, using Roman Numerals (shown in brackets: I, II, III, IV).

In February 2015, the Drug Utilisation Sub-Committee (DUSC) of the Pharmaceutical Benefits Advisory Committee (PBAC) reviewed the Pharmaceutical Benefits Scheme (PBS) utilisation of PAH medicines. The DUSC considered that the PBS restrictions for PAH medicines were not consistent with current treatment guidelines as:

Patients with PAH WHO Functional Class (FC) III symptoms with a mean right arterial pressure of 8 mm Hg or less were required to trial -at least six weeks of appropriate vasodilator medicine without an adequate response before accessing a PAH.
Treatment of patients with PAH WHO FC II symptoms was not allowed.
Combination therapy was not subsidised.

In July 2015, the PBAC considered a submission from the sponsor of bosentan, epoprostenol and macitentan to remove the requirement for patients to be assessed as having achieved a response to treatment for continuing access to these medicines. The submission claimed that the PBS restriction requiring ongoing evidence of improvement or stability in disease status was inconsistent with best clinical practice and international guidelines. The submission further argued that in the case of an inadequate response to initial therapy, guidelines recommended sequential combination therapy, rather than cessation or switching between therapies as was required by the PBS restrictions. Noting the submission’s claim that the PBS continuing restriction for PAH medicines was inconsistent with best clinical practice and international guidelines, the PBAC considered that there were several issues around PAH medicines that could not be assessed within the scope of the submission.

Further information is available in the July 2015 PBAC Public Summary Documents for the combined bosentan, epoprostenol and macitentan submission.

In December 2015, the PBAC recommended a Post-market Review (PMR) of the efficacy and cost‑effectiveness of PAH medicines, including the existing listings for patients with WHO FC III and IV symptoms, and the expanded use of these therapies as recommended in international guidelines.

The purpose of the PMR was to review the safety, efficacy (treatment benefit) and cost-effectiveness of these medicines, in the context of patient access to optimal treatment and Quality Use of Medicines.

The PMR was approved by the then Minister for Health on 7 April 2016 and was carried out under the Australian Government’s post-market monitoring program, which aims to ensure the continued safe, cost-effective and Quality Use of Medicines listed on the PBS.

Medicines included in the PAH Review were:

Table 1. PBS-listed PAH medicines included in the PMR*
Medicine Class	PBS listed medicines generic drug name
endothelin receptor antagonists (ERAs)	ambrisentan, bosentan monohydrate, macitentan
phosphodiesterase type 5 inhibitors (PDE-5i)	sildenafil, tadalafil
prostanoids	epoprostenol sodium, iloprost
soluble guanylate cyclase stimulators (sGC stimulator)	riociguat

Selexipag, first PBS-listed 1 February 2021, was not included in the PMR.

Reference Group

Name Nominating Body	Role	Expertise
Professor Terence Campbell PBAC	Chair	Pharmaceutical benefits policy, cardiology
Professor Anna Kemp-Casey DUSC	Individual - Technical Expert	Drug utilisation
Professor Susanna Proudman	Individual - Technical Expert	Pulmonary disease
Professor Trevor Williams	Individual - Technical Expert	Pulmonary disease
Ms Michelle Tew Australian Health Economics Society	Technical Expert	Health economics
Dr Eugene Kotlyar Cardiac Society of Australia and New Zealand	Organisational representative	Cardiac disease
Professor Garry Jennings Heart Foundation	Organisational representative	Cardiology
Ms Elizabeth De Somer Dr Vicki Gardiner Medicines Australia	Organisational representative	Pharmaceutical Industry
Professor Geoff Strange Pulmonary Hypertension Society of Australia and New Zealand	Organisational representative	Pulmonary disease
Dr Charlotte Hespe Royal Australian College of General Practitioners	Organisational representative	General practice
Mr Garth Birdsey Society of Hospital Pharmacists	Organisational representative	Hospital pharmacy
Dr Jane Cook Dr Grant Pegg Therapeutic Goods Administration	Organisational representative	Regulation and safety of medicines
Dr Jeremy Wrobel Thoracic Society of Australia and New Zealand	Organisational representative	Pulmonary disease
Dr Christine Walker Consumers’ Health Forum	Organisational representative	Health consumer advocacy

Final Terms of Reference

The PBAC considered the draft Review Terms of Reference (ToR) and comments from stakeholders at the August 2016 PBAC special meeting. Following the August 2016 PBAC special meeting the then Minister for Health approved the final Terms of Reference for the Review:

Review recent clinical guidelines for the management of PAH and compare this to the PBS restrictions and Therapeutic Goods Administration (TGA) indications for the use of PAH medicines.
Review the utilisation of PAH medicines in Australia, including sources of data that can provide additional information on clinical use that is not available from PBS data.
Review the clinical outcomes that are most important or clinically relevant to patients with PAH, and the extent to which these outcomes are included in the evidence previously considered by PBAC.
Collate and evaluate evidence on the comparative effectiveness of PAH medicines, including combination use and use in the WHO functional class II patient populations.
Following ToR 1-4 consider reviewing the cost-effectiveness of existing PBS listings for PAH medicines, and in treatment of WHO functional class II and combination treatment in class III and class IV patients.

Public Submissions addressing the final Terms of Reference (closed)

The public submission process for the Pulmonary Arterial Hypertension (PAH) Medicines Review was open between 13 February 2017 and 27 March 2017. To view submissions please go to the Public Consultation page.

Consumer Session

A consumer session was held in Sydney on 14 October 2017 with members of the Pulmonary Hypertension Association Australia (PHAA). To view the Consumer Outcome Statement please go to the Public Consultation page.

Public Consultation on the Draft Review Report (closed)

Public Consultation on the draft Review Report was open between 21 May 2018 and 10 June 2018.

Post-market Review of PAH Medicines – Final Report to the PBAC

The Final Report is provided in ten parts in DOCX and PDF format. ‘Commercial-in-confidence information has been redacted.

PBAC Consideration of the Final Report

The PBAC considered the PMR of PAH Final Report in November 2018, including PBAC sub-committee advice and stakeholder comments. Parts of the PBAC Minutes have been redacted due to ‘Commercial-in-confidence’ information.

November 2018 PBAC Minutes (PDF 1136 KB) – (Word 85 KB)

PBAC Consideration of PBS PAH medicine restriction changes arising from the Post-market Review

Over several meetings between March 2019 and March 2022, the PBAC considered and recommended changes to PBS restrictions for PAH medicines to improve patient access and align PBS restrictions more closely with clinical guidelines.

Parts of the PBAC minutes have been redacted due to ‘Commercial-in-confidence’ information.

Plain Language Summary

A brief plain language summary (PDF 204 KB) – (Word 41 KB) of PMR outcomes for consumers is available.

Review Process

This Review followed the Post-market Review Framework available on the Reviews website. This process included public consultation on the draft Terms of Reference, an opportunity to provide submissions to the Review, and an opportunity to comment on the draft Review Report.

Further Information

Further information on post-market reviews is available on the Reviews website.

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