Decision to fund mepolizumab (Nucala) for the treatment of patients with severe refractory eosinophilic asthma

12 March 2020

Medicines Decision

We are pleased to announce a decision to fund mepolizumab (Nucala) from 1 April 2020 for the treatment of severe refractory eosinophilic asthma, through an agreement with GlaxoSmithKline NZ Limited (GSK).

We estimate that about 500 patients will benefit from treatment.

The agreement with GSK also includes amendments to the contractual arrangements for warfarin sodium (Marevan) and for lamotrigine (Lamictal) 2 mg and 5 mg tablets. There will be no changes to the funding status of these products, but the price will change.

Any changes to the original proposal?

This decision was subject to a consultation letter dated 18 December 2019.

Following the consultation feedback, we have made some changes to the Special Authority criteria that were consulted on. The two main changes are that:

Clinical immunologists will be able to complete the Special Authority application form for mepolizumab; and
Patients currently receiving single combination ICS/LABA inhaler Maintenance and Reliever Therapy (SMART) will be able to receive mepolizumab if all other criteria are satisfied.

Who we think will be most interested

People with severe eosinophilic asthma and their whānau
Respiratory physicians, respiratory nurses, clinical immunologists, and other clinicians involved in the management of severe eosinophilic asthma.
Hospital pharmacists
Pharmaceutical suppliers

Details about this decision

Mepolizumab (Nucala) will be listed in Section B and in Part II of Section H of the Pharmaceutical Schedule from 1 April 2020 at the following price and subsidy (ex-manufacturer, excluding GST):

Chemical	Formulation	Brand	Pack size	Price and subsidy
Mepolizumab	Inj 100 mg vial	Nucala	1	$1,638.00

A prefilled syringe form and an autoinjector form of Nucala 100 mg will also be listed in the Pharmaceutical Schedule at the same price and subsidy as soon as possible following Medsafe approval.

A confidential rebate will apply to Nucala that will reduce the net price to the Funder and Nucala will have protection from delisting and subsidy reduction until 31 March 2023.

Mepolizumab will be listed in Section B of the Pharmaceutical Schedule subject to the following Special Authority criteria:

Special Authority for Subsidy

Initial application – (Severe eosinophilic asthma) only from a respiratory physician or clinical immunologist. Approvals valid for 12 months for applications meeting the following criteria:

All of the following

Patient must be aged 12 years or older; and
Patient must have a diagnosis of severe eosinophilic asthma documented by a respiratory physician or clinical immunologist; and
Conditions that mimic asthma eg. vocal cord dysfunction, central airway obstruction, bronchiolitis etc have been excluded; and
Patient has a blood eosinophil count of greater than 0.5 x 10^9 cells/L in the last 12 months; and
Patient must be adherent to optimised asthma therapy including inhaled corticosteroids (equivalent to at least 1000 mcg per day of fluticasone propionate) plus long acting beta-2 agonist, or budesonide/formoterol as part of the single maintenance and reliever therapy regimen, unless contraindicated or not tolerated; and
Either:

6.1. Patient has had at least 4 exacerbations needing systemic corticosteroids in the previous 12 months, where an exacerbation is defined as either documented use of oral corticosteroids for at least 3 days or parenteral steroids; or
6.2. Patient has received continuous oral corticosteroids of at least the equivalent of 10 mg per day over the previous 3 months; and

Patient has an Asthma Control Test (ACT) score of 10 or less. Baseline measurements of the patient’s asthma control using the ACT and oral corticosteroid dose must be made at the time of application, and again at around 52 weeks after the first dose to assess response to treatment.

Renewal – (Severe eosinophilic asthma) only from a respiratory physician or clinical immunologist. Approvals valid for 2 years for applications meeting the following criteria:

Both:

An increase in the Asthma Control Test (ACT) score of at least 5 from baseline; and
Either:

2.1. Exacerbations have been reduced from baseline by 50% as a result of treatment with mepolizumab; or
2.2. Reduction in continuous oral corticosteroid use by 50% or by 10 mg/day while maintaining or improving asthma control.

The same restrictions will apply in Part II of Section H of the Pharmaceutical Schedule (the Hospital Medicines List; HML).

Other changes associated with this decision

As part of this decision, protection from delisting and subsidy reduction until 31 March 2023 will also be provided for the following treatments that are currently supplied by GSK:

warfarin sodium (Marevan) 1 mg, 3 mg and 5 mg tablets
lamotrigine (Lamictal) 2 mg and 5 mg dispersible tablets

Marevan will continue to be listed in Section B and Part II of Section H of the Pharmaceutical Schedule with a change in price and subsidy from 1 April 2020 as follows (ex-manufacturer, excluding GST):

Chemical	Formulation	Brand	Pack size	Current price and subsidy	New price and subsidy
Warfarin sodium	Tab 1 mg	Marevan	100	$7.60	$6.46
Warfarin sodium	Tab 3 mg	Marevan	100	$11.80	$10.03
Warfarin sodium	Tab 5 mg	Marevan	100	$13.50	$11.48

Lamictal 2 mg and 5 mg dispersible tablets will continue to be listed in Section B and Part II of Section H of the Pharmaceutical Schedule with a change in price and subsidy from 1 September 2020 as follows (ex-manufacturer, excluding GST):

Chemical	Formulation	Brand	Pack size	Current price and subsidy	New price and subsidy
Lamotrigine	Tab dispersible 2 mg	Lamictal	30	$6.74	$55.00
Lamotrigine	Tab dispersible 5 mg	Lamictal	30	$9.64	$50.00

Our response to what you told us

We appreciate the time people took to respond to this consultation.

All consultation responses received were considered in their entirety in making the decision to fund mepolizumab for the treatment of severe refractory eosinophilic asthma.

Responses were generally supportive of the proposal. A summary of the main themes raised in feedback and our responses to the feedback are set out below:

Theme	Comment
Some responders considered that an ACT score should not be an initial or renewal criterion, as this is not aligned with the evidence which shows changes in oral corticosteroid use and exacerbations (as clinical outcomes related but separate to asthma control), where the purpose of mepolizumab is to reduce severe exacerbation risk, not improve asthma control.	The Respiratory Subcommittee of the Pharmacology and Therapeutics Advisory Committee (PTAC) discussed the ACT-related criteria in detail and recommended the ACT instrument as a validated instrument with good diagnostic accuracy for the self-reported assessment of controlled and poorly controlled asthma, and as easily accessible to patients and clinicians in New Zealand [PDF, 397 KB] ACT scores are used in the Special Authority criteria for omalizumab. However, PHARMAC intends to seek further clinical advice in future on the ACT criteria for mepolizumab.
Some responders suggested amending the Special Authority criterion to include patients using budesonide-formoterol as maintenance and reliever therapy (SMART regimen). They also suggested SMART be trialled before mepolizumab can be used, as there is very good evidence that SMART is appreciably more effective than combined ICS/LABA maintenance with SABA reliever therapy in reducing the risk of severe exacerbations. They also considered the eligibility criteria for optimal baseline treatment of very high dose ICS plus LABA require doses of ICS that are not evidence-based and are clinically inappropriate.	Following consultation, the Special Authority criteria have been amended to permit patients using SMART to receive mepolizumab if all other criteria are satisfied. SMART is currently a widely used treatment regimen for patients with asthma, and is the preferred ICS/LABA regimen for patients at risk of severe asthma exacerbations(external link) However, with respect to trialling the SMART regimen before mepolizumab: We are aware that national guidelines are increasingly urging the use of SMART for moderate to severe asthma, and use of lower doses of maintenance ICS (where what was considered ‘low’, ‘standard’ and ‘high’ ICS doses are now considered standard to very high). However, we consider that patients with severe eosinophilic asthma refractory to maximal fixed dose ICS with LABA maintenance treatments should remain eligible, noting that current national guidelines include the commonly-used fixed dose ICS plus LABA treatments as well as the devices used in SMART regimens. There may be a case for considering changing the high baseline ICS thresholds; PHARMAC intends to seek further clinical and sector feedback on the ICS-related entry criterion (thresholds and/or their removal or replacement with SMART) in future.
The Special Authority criterion of >500 cells/µl should be changed to ≥500 cells/µl, as NZ laboratories report eosinophils to the nearest 100 cells/µl (0.1x10^9 cells/L)	The intent of the Special Authority criterion is to include patients who have an eosinophil count of >500 cells/µl. The suggested amendment would result in patients with an eosinophil count >450 cells/µL being eligible for treatment. The units used in the Special Authority criteria have been altered to align with the expected laboratory format (0.5x10^9 cells/L).
Some responders considered that clinical immunologists should be able to complete the initial and renewal Special Authority for mepolizumab as they are also responsible for the care of patients with severe eosinophilic asthma.	As a result of this feedback, we have amended the Special Authority criteria to allow for both clinical immunologists and respiratory physicians to complete initial and renewal Special Authority applications for mepolizumab.
Various other changes to the criteria were suggested that would provide wider access to mepolizumab, including removal of the requirement for a high eosinophil count, reducing the eosinophil count (≥ 300cells/µL), including combined eosinophilic asthma and recurrent nasal polyp disease/sinusitis, and including eosinophilic granulomatosis with polyangiitis (EGPA).	The Special Authority criteria relating to these requests are in line with our clinical advice [PDF, 397 KB] We would welcome a funding application to widen access to people with an eosinophil count of ≥ 300cells/µL in the past 12 months if evidence becomes available that supports this change. We note that mepolizumab is not currently approved by Medsafe for combined eosinophilic asthma and nasal polyp disease/sinusitis, but would welcome a funding application for this group in the future if mepolizumab gains Medsafe approval for this condition.

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.