Decision to fund oncology, multiple sclerosis and respiratory treatments

Medicines

Decision

We’re pleased to announce a decision to approve funding for oncology, multiple sclerosis and respiratory treatments.

In summary, this will result in the following changes from 1 December 2019:

Any changes to the original proposal?

This decision was subject to a consultation letter dated 7 August 2019

The proposed terms of listing, including commercial terms and Special Authority criteria, were approved as consulted on without any changes except as a result of consultation feedback, the Special Authority criteria and restrictions for trastuzumab emtansine were amended to:

  • allow pre-treatment with trastuzumab and chemotherapy other than a taxane
  • remove the criterion for left ventricular ejection fraction (LVEF) (heart function)
  • clarify the intent regarding treatment of patients with brain metastases

This means that trastuzumab emtansine will be funded from 1 December 2019 for patients with HER-2 positive metastatic breast cancer who meet the following Special Authority criteria (differences from criteria consulted on shown by additions in bold and deletions in strikethrough):

Initial application - only from a relevant specialist or medical practitioner or on the recommendation of a relevant specialist. Approvals valid for 6 months for applications meeting the following criteria:

All of the following:

  1. Patient has metastatic breast cancer expressing HER-2 IHC 3+ or ISH+ (including FISH or other current technology); and
  2. Patient has previously received trastuzumab and a taxane chemotherapy, separately or in combination; and
  3. Either

3.1.    The patient has received prior therapy for metastatic disease*; or
3.2.    The patient developed disease recurrence during, or within six months of completing adjuvant therapy*; and

  1. Patient has a good performance status (ECOG 0-1); and
  2. Patient has left ventricular ejection fraction of 50% or more; and
  3. Patient does not have symptomatic brain metastases; and
  1. Either:

5.1.  Patient does not have symptomatic brain metastases; or
5.2.  Patient has brain metastases and has received prior local CNS therapy; and

  1. Treatment to be discontinued at disease progression.

Renewal – only from a relevant specialist or medical practitioner or on the recommendation of a relevant specialist. Approvals valid for 6 months for applications meeting the following criteria:

Both:

  1. The cancer has not progressed at any time point during the previous approval period whilst on trastuzumab emtansine; and
  2. Treatment to be discontinued at disease progression.

*Note: Prior or adjuvant therapy includes anthracycline, other chemotherapy, biological drugs, or endocrine therapy.

Who we think will be most interested

  • People who have or may develop lung cancer, breast cancer, multiple sclerosis or idioathic pulmonary fibrosis and their whānau

  • Oncologists, neurologists and respiratory clinicians

  • Community and hospital pharmacies

  • DHBs

  • Organisations with an interest in treatments for cancer, multiple sclerosis or respiratory diseases.

Our response to what you told us

We’re really grateful for the time people took to respond to this consultation. We had a large number of responses, most responses were really supportive of the proposal.

A summary of the main themes raised in feedback, our responses to the feedback received, and changes we have made after listening to you are set out below.

Feedback theme

Comment

Alectinib for ALK-positive advanced non-small cell lung cancer (NSCLC)

ALK testing

Clarification of the definition of an appropriate ALK test

It would be up to DHB services and clinicians to determine what an appropriate ALK test may be. The Lung Oncology Special Interest Group (LOSIG) supports the phrasing of the funding criteria. It considers the establishment of affordable and equitable access to testing is a DHB decision; and indicated it would help to develop a consistent national approach.

Concern regarding the costs associated with and availability of ALK-testing.

PHARMAC does consider the cost of testing in its assessment of impacts to the health sector, however notes that DHBs are responsible for the provision and funding of testing services.

Wider access

A request for amendment to the renewal criteria to remove the requirement to use RECIST criteria to measure response to treatment.

We note that the criteria are in line with clinical advice.

No changes have been made to the criteria consulted on for alectinib.

We consider that RECIST criteria provide an objective measure of response and disease progression which is well understood in the oncology community.

Trastuzumab emtansine for HER2-positive metastatic breast cancer

Wider access

Requests for amendment to the criteria to allow patients previously treated with vinorelbine rather than a taxane to be eligible.

 

The intent of the proposed criteria is to provide a second-line or beyond treatment option for all previously-treated HER2-positive advanced breast cancer patients.

Clinical advice from members of CaTSoP indicated that this would be an appropriate amendment. The criteria for trastuzumab emtansine have been amended to reflect this.

 

Requests for amendment to the proposed criteria regarding cardiac function to reduce to 40% or remove the requirement for left ventricular ejection fraction (LVEF) of 50% or more.

 

Our clinical advisors considered it is reasonable to remove this requirement from the Special Authority criteria.

The criteria have been amended to reflect this.

 

Requests for amendment to the proposed criteria to remove of the criteria which requires patients not to have symptomatic brain metastases.

 

Clinical advice from members of CaTSoP recommended clarifying the proposed criteria to detail that if brain metastases are present then these should be previously treated and at least stable prior to accessing trastuzumab emtansine.

The criteria have been amended to reflect this.

System and resource impacts

Feedback about resource impacts in terms of:

  • infusion and imaging services,
  • need for assessment of LVEF function,
  • health professional time to manage patients
  • support services time to update protocols and patient information

 

PHARMAC assesses and considers all additional costs to the health sector, however notes that DHBs are responsible for the provision and funding of services.

We note that the requirement for cardiac function assessment via LVEF measurement has been removed from the criteria based on consultation feedback.

 

Request for clarification of how patient numbers were estimated.

 

The eligible population of second-line HER2 positive advanced breast cancer of 60 patients per year was estimated based on:

  • the total number of patients seeking a second-line treatment following pertuzumab/trastuzumab in a first line setting, using rates from the trial evidence; and
  • the expected prevalent population of patients who would not have received pertuzumab (as were pre-treated prior to its listing for treatment naïve patients) and would be seeking additional treatment.

Request for clarification of the frequency of response assessment.

 

The frequency of assessment is a matter for clinical decision-making and should ensure the clinically appropriate management and monitoring of patients.

Ocrelizumab for relapsing remitting multiple sclerosis

Wider access

Respondents raised a number of aspects relating to entry and exit criteria. Requests for wider access included:

  • The stopping criteria be expanded to EDSS 6.0 or 6.5 irrespective of starting points
  • The gradient scale be removed from the stopping criteria
  • The starting criteria of EDSS 0-4 be removed
  • The starting criteria allow for treatment of those with clinically isolated syndrome (CIS) who meet the McDonald 2017 diagnostic criteria for RRMS

 

Funding applications for MS treatments have undergone extensive review by PTAC. PTAC considered that these treatments should be targeted to the patients likely to benefit most from such treatments. The entry and exit criteria are based on PTAC’s advice; that treatment should be targeted to patients with clinically definite RRMS with active inflammatory disease. Should new evidence become available we would be happy to seek further advice from PTAC.

With regards to the stopping criteria; we are currently working on analysis, to determine what the cost-effectiveness and budget impacts would be of amending the stopping criteria to 4.5, 5.5 and 6.0 for all patients. We are aiming to have this considered by PTAC at its November 2019 meeting.

Further details on the clinical advice we have received to date on this are available from the application tracker.

With regards to the removing the starting criteria; should new evidence become available we would be happy to seek further advice from PTAC.

We note that PTAC has recommended that funding be declined for earlier disease such as those with clinically isolated syndrome (CIS). Should new evidence become available we would be happy to seek further advice from PTAC.

Further details on the clinical advice we have received are available from the application tracker.(external link)

Ocrelizumab should also be funded for people with primary progressive multiple sclerosis (PPMS), and requests that PTAC re-visit its recommendation to decline.

PTAC considered ocrelizumab for the treatment of PPMS at its February 2018 meeting, and recommended that the application for this indication be declined. The reason for this was primarily around the lack of data to establish both the safety and efficacy of ocrelizumab for people with PPMS. The Committee noted that there are more studies that are ongoing which may address some of these concerns.

Full details of the minutes are available from the application tracker.(external link)

Given there is no new evidence provided with this submission we will not be asking PTAC to re-review its recommendation at this stage. We would be happy to seek further advice from PTAC should new studies, once published, address PTACs concerns.

Request that PTAC review MSNZ’s June 2018 submission, regarding wider access, in full at its November 2019 meeting.

PTAC reviewed an earlier submission from MSNZ (November 2017) and referred an update to the submission (the MSNZ June 2018 submission) to the Neurological Subcommittee (SC), so that it could be considered by experts in the treatment area. The SC considered the MSNZ submission at its July 2018 meeting. The SC minutes provided to PTAC were an extensive summary of the discussion on the submission.

Considered that both the Neurological Subcommittee and MSTAC were supportive of the submission to wider access but that PTAC declined without seeing the submission.

We are aiming for PTAC to look at MS Treatments at its November 2019 meeting and will attach a full copy of the MSNZ’s June submission for PTAC’s information.

The current access criteria are based around physical mobility. The ability to mobilise /walk is only one aspect that affects people with MS; the criteria (utilising EDSS) should be reviewed to cater for the whole person and not just one aspect of the disease.

Amending access criteria to include an additional measurement scale has been considered by the Neurological SC and PTAC, most recently in November 2018, and the proposed access criteria change was recommended for decline. In summary the clinical advice we have received is that measurement scales other than EDSS are impractical and would likely lead to patients stopping treatment earlier, as they are potentially more sensitive to disease progression at higher EDSS states.

Full details of the minutes are available from the application tracker.(external link)

Funding to start earlier than 1 December

People who are JCV positive would like to be able to access treatment earlier than 1 December. Noted 1 December is a Sunday, so it is impractical to receive an infusion on this day.

We understand the desire for patients to access treatment as early as possible, however the implementation date balances the steps required to appropriately undertake public consultation, consider responses and make a decision as well as the need to allow sufficient time for DHBs to put in place the systems and services to deliver these new treatments.

We understand that Roche has put in place a free-stock program via DHBs to provide access to treatment for patients who meet the access criteria detailed in the consultation document, ahead of the decision or listing date.

Other

NZers who are self-funding or who are receiving funded treatment with ocrelizumab overseas would be able to receive publicly funded treatment in NZ

Patients who are self-funding their treatment, or receiving treatment overseas, would be assessed on a case by case basis to determine their eligibility for funded treatment, including with reference to the entry criteria that were met (or not) when the patient was initiated on treatment, and whether or not the stopping criteria are met.

Any applications should be submitted via the MS treatments application process.

Disappointment in the length of time it has taken to fund ocrelizumab. Ocrelizumab was approved by Medsafe in Dec 2017 and was recommended for funding by PTAC in November 2018. It then took 8 months for the cost-negotiation process to begin.

Ocrelizumab has been funded in other OECD countries for much longer:

  • USA – March 2017
  • Europe – Jan 2018
  • Australia – Feb 2018
  • UK – June 2018

PTAC advised that ocrelizumab is likely to have similar, but not superior, efficacy to the ‘newer’ multiple sclerosis treatments and that it should only be funded if cost-neutral to the other newer MS treatments.

PHARMAC has actively worked on the funding application for ocrelizumab during the time period since November 2018. We focus our resources on medicines that offer the best health outcomes; including those considered a higher priority and where there are no funded alternatives.

Would like PHARMAC to provide evidence that supports the current access criteria.

As noted above funding applications for MS treatments have undergone extensive review by PTAC; the entry and exit criteria are based on PTAC’s advice.

Details of the evidence reviewed by PTAC and its Subcommittees are available in the relevant minutes linked to the application tracker. (external link)

PHARMAC should be more proactive with treatments that have been proven to have a success rate internationally and offer these to patients with MS. Especially those treatments that are available in the UK and Australia.

PHARMAC works within a fixed budget that will never enable every available pharmaceutical to be funded. Our role is to make choices in order to get the best health outcomes for NZers we can from the money available. To do this we seek advice from our own clinical experts and then assess each medicine and compare it against all other options.

Neurologists shouldn’t have to fill out forms to access funding for MS treatments, they should be trusted to prescribe within the guidelines set by PHARMAC.

MS treatments are very expensive and so funding is restricted to those people who will benefit most from treatment. PHARMAC manages a panel of expert neurologists (MSTAC) to assess whether a patient meets the Special Authority criteria and is eligible for funding. This is necessary due to the complexities of the disease; the panel ensures nationally consistent and equitable access.

Pirfenidone for idiopathic pulmonary fibrosis

Criteria should be amended to remove the requirement to stop pirfenidone if Forced Vital Capacity (FVC) declines by >10% over 1 year or if FVC falls below 50% predicted as both these patient groups do better if they remain on therapy.

The criteria are in line with advice from our clinical advisors and match those for nintedanib. For patients who do not experience disease progression, defined as a less than 10% decline in predicted FVC, then patients remain eligible for ongoing subsidised treatment.

We welcome a funding application with supporting evidence for widened access to pirfenidone (and/or nintedanib).

General responses

One responder considered that PHARMAC needs to review its processes to ensure treatments which are supported by evidence of benefit are made available sooner.

We are committed to making our funding application assessment and decision-making processes faster, clearer and simpler. A number of activities are currently underway.

One responder noted the importance of considering wider system impacts for DHBs particularly radiology. Considered that the proposal would result in increased imaging requirements which the DHBs may struggle to provide in a timely and equitable way due to demand capacity mismatch.

We acknowledge the impact of our decisions on the DHBs, which are responsible for the provision and funding of testing services. We do consider the costs the wider health sector, including for imaging requirements, and we have been actively engaging with DHBs to ensure that we are accurately capturing and quantifying this impact.

Three responders requested funding for pharmaceuticals or indications not included in the proposal:

  1. crizotinib for ROS-1 NSCLC
  2. immunotherapy treatments for NSCLC without mutations
  3. a CDK4/6 inhibitor for the treatment of breast cancer
  1. We welcome a funding application for crizotinib for the treatment of ROS-1 NSCLC patients
  2. We plan to issue an RFP for immunotherapy treatments (including pembrolizumab, nivolumab and atezolizumab) for use in both first and second-line settings for the treatment of NSCLC later in 2019.
  3. A RFP has recently been issued for CDK4/6 inhibitors for the treatment of advanced breast cancer. This could result in funding of one of these agents by early 2020.

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.