PHARMAC decision on the funding of haemophilia treatments

Lack of transparency regarding magnitude of savings and details of RFP bids to allow others to weigh up this proposal over other possible funding scenarios for these haemophilia treatments.

The majority of the savings obtained in this proposal are via confidential rebates, so PHARMAC is unable to provide further detail on the magnitude of savings involved. Although PHARMAC prefers transparent pricing, the ability for suppliers to provide confidential rebates does enable PHARMAC to obtain better net pricing for products.

Due to the commercial sensitivity of the RFP process, it is difficult to involve all stakeholders in the RFP evaluation process. PHARMAC however sought the expert advice of haemophilia treaters on the Haematology Subcommittee of PTAC as part of this process. Relevant medical and commercial information were disclosed to them to enable them to provide a recommendation to PHARMAC.

PHARMAC should be able to negotiate these prices without a need to switch a large number of patients. New patients could be started on the preferred brand and existing patients be given an option to switch.

PHARMAC notes that lowest prices are offered by suppliers when there is greater certainty of market share. This is observed through PHARMAC’s competitive procurement processes, including this RFP for haemophilia treatments where the greater the market share, the lower the prices that were offered. Given that there are only a small number of new haemophilia patients beginning treatment each year, it would not be possible to achieve the market share required to obtain the most cost-effective prices without a brand switch. We note that brand switches involving large patient numbers have occurred in Australia and the UK to obtain the pricing of treatments there.

The proposal essentially restricts routine rFVIII use to one brand. This leaves the New Zealand haemophilia population vulnerable to the impact of severe unplanned shortages of the Preferred Brand for example in the event of a product recall due to quality issues. A 50:50 market split would be safer. It would be very difficult to source alternative product for such a large number of patients within such a short time.

In 2001, there was a worldwide shortage with Kogenate FS due to quality issues requiring patients to be switched back to plasma-derived products.

For many life-saving essential medicines in New Zealand, only one brand is funded, often following a competitive process. Drawing from the experience of supply security for these other medicines, PHARMAC considers that having multiple brands of a product in a market does not improve security of supply.  When there are limited or only one supplier, forecasting of stock requirements is more accurate which helps prevent out-of-stock situations.

Further, in exchange for market exclusivity, the supply contracts we have in place for these haemophilia treatments require suppliers to agree to rigorous conditions to prevent and manage potential out-of-stocks. This includes significant stock-holding, frequent stock reporting to PHARMAC and a commitment to source a suitable alternative to prevent a potential out-of-stock occurring.

PHARMAC notes that there are now significantly more alternative brands of rFVIII (PHARMAC is aware of 4 others besides Xyntha) available when compared to the shortage that occurred in 2001.

There is currently uncertainty in what proportion of patients would seek funding to remain on Kogenate FS or Advate after 1 March 2016. PHARMAC will monitor the brand switch and work with clinicians and relevant suppliers to ensure the risk of an out-of-stock situation with Xyntha, Kogenate FS and Advate is mitigated as much as possible.

There was feedback supporting the establishment of the Haemophilia Treatments Panel and also against it.

If the Panel was established, its role should be limited to the administration of funding for the rFVIII products only as a result of the RFP. It should not take over the role of the Haemophilia Treaters Group (HTG).

Some felt that there is no need to establish another Panel to manage the funding for Kogenate FS and Advate as this role could be carried out by the HTG.

Some patients also questioned whether it would be possible to have a patient representative on the Panel.

The role of the Panel will be limited to administering access to two specific brands of rFVIII, Kogenate FS and Advate, based on criteria approved by PHARMAC.

To preserve the integrity and objectivity of the Panel, its determinations will be made by consensus and Panel members will not participate in assessing applications involving patients in their care or from their treatment centres. The Chair of the Panel will be a senior clinician from another specialty which will help facilitate discussions.

Although the HTG could potentially coordinate such a change, due to the 6 month transition period PHARMAC considers that a representative smaller group of clinicians will be more agile and easier to administer. Because funding for patients will need to be considered on a case-by-case basis, funding decisions made by a Panel will enhance national consistency and enable greater objectivity in decision-making.

Because the Panel will be determining funded access based on clinical criteria, it is appropriate that its membership is comprised of clinicians. A patient representative on the group would make it difficult to discuss individual patients’ medical histories.

The proposed list of clinical situations, where a switch to Xyntha may not be clinically appropriate, is not exhaustive and consideration should be given to patients with other clinical situations which may make a switch to Xyntha difficult or clinically inappropriate.

We note that the list in the consultation letter is not exhaustive. PHARMAC will have discretion to consider funding Kogenate FS and Advate for patients in other clinical situations on an individual basis and it will take advice from the Haemophilia Treatments Panel in such cases.

There are some haemophilia patients with gene mutations which increase their risk of inhibitor development, even beyond 50 exposure days. This proposal could potentially put them at risk of inhibitor development.

Kogenate FS and Advate will be able to be accessed by patients who are unable to switch to Xyntha for clinical reasons.

Applications for funding of Kogenate FS or Advate for these patients can be made to the Haemophilia Treatments Panel.

There has been recent published information suggesting that the risk of inhibitor development is increased with Kogenate FS use.

This issue was reviewed by the Medicines Adverse Reactions Committee (MARC) at Medsafe during its March 2015 meeting. MARC considered that there was insufficient evidence to support a difference in the risk of inhibitor development when patients are treated with different factor VIII products.

Has there been adequate consideration of the possibility of increased inhibitor risk with B-domain deleted molecules like Xyntha when compared to full length molecules like Advate?

PHARMAC’s Haematology Subcommittee advised that there was no clinical reason not to award Preferred Brand Status to Xyntha when it evaluated the RFP bids. The Haemophilia Treaters Group also did not raise clinical concerns about Xyntha when it was consulted by PHARMAC at various times when developing the RFP. Xyntha is registered for use in New Zealand by Medsafe with similar indications to Advate and Kogenate FS.

It is unclear from the consultation letter if there will be adequate monitoring of inhibitor levels in patients during the brand switch and will the required treatment be provided for patients who do develop inhibitors as a result of this brand switch?

Patients would need to be closely monitored for inhibitors during the brand switch.

The clinical advice we have received indicates that patients would have about four additional blood tests to monitor for inhibitors.

Our clinical advice is that, based on experience overseas, the risk of developing inhibitors as a result of a brand switch is very low. However, if patients do develop inhibitors, they would be provided with the required treatment.

Can there be special consideration for funding of Advate or Kogenate FS for patients under the age of 18 to minimise the risk of this brand switch to them, and provide them with the best chance of a normal life in adulthood?

The Haemophilia Treatments Panel and PHARMAC will have discretion to consider funding of Kogenate FS and Advate for patients where it is demonstrated that a brand switch would jeopardise appropriate clinical care.

A six-month transition would be adequate to coordinate a brand switch for most patients.

There would need to be consideration of additional support for patients who live further away from their treatment centres and need to travel to attend clinics for counselling through the brand switch.

There should be allowance of a longer transition period for patients who need longer to adjust. This could be for clinical or psychosocial reasons.

PHARMAC will work closely with haemophilia treatment centres and the Haemophilia Foundation of New Zealand to help ensure that patients receive the support they need as they undergo this change.

This proposal is against the long-held patient principle of product choice.

Sole brand medicine funding is commonplace in New Zealand. There are multiple examples in the Pharmaceutical Schedule were only one brand of a medicine is subsidised. In such circumstances patients could choose to use a different brand, although that brand would not be funded unless there was a clinical reason why the funded brand could not be used.

This decision provides sufficient treatment choice to meet clinical need, as funding for Kogenate FS and Advate is available for patients whose treatment would be compromised if switched to Xyntha. In addition, the savings that will result from this decision will enable better health outcomes to be achieved for all New Zealanders by releasing funding that will be spent on other pharmaceuticals.

The savings obtained from this proposal should be used to fund additional haemophilia services (physiotherapy, specialist nurses, IVF pre-implantation diagnosis) and more or new haemophilia treatments (tolerisation of more patients or prophylaxis with bypassing agents for patients with inhibitors) instead of being channeled to the Combined Pharmaceutical Budget (CPB).

Previously the NHMG was able to do this and it resulted in an efficient system which was world-leading. There is good evidence that adequate physiotherapy reduces requirement for treatment and reduces long-term complications from haemophilia.

There is a risk that this proposal would diminish the role of the NHMG, resulting in it being inadequately funded and unable to provide comprehensive care to patients.

In 2013, in consultation with DHBs, PHARMAC decided that rFVIII, rFIX, rFVIIa and FEIBA would be funded from within the CPB, because it was in line with PHARMAC’s role in managing the funding of medicines in New Zealand. It is not within PHARMAC’s remit to fund haemophilia services from the CPB.

The funding of plasma-derived products and haemophilia services continues to be managed by the NHMG.

Whilst the inclusion of the recombinant products within the CPB means the NHMG cannot reinvest savings from this decision into haemophilia services; it does mean that additional funding requests to DHBs are not required when a patient requires large amounts of rFVIII for surgery or to manage an acute bleed.

Whilst tolerisation can and is being funded from the CPB, prophylaxis with rFVIIa and FEIBA is a significant change from current clinical practice in New Zealand. PHARMAC has not formally assessed the risk and benefits of changing clinical practice in this way and would be willing to consider a funding application for this use.

Other than the establishment of the Haemophilia Treatments Panel to administer funded access to rFVIII, there will be no changes to the role of the NHMG as a result of this decision.

This proposal would result in pharmaceutical suppliers withdrawing their product and their funding of haemophilia services from New Zealand.

It also reduces the incentive for these suppliers to continue to fund research in this therapeutic area.

PHARMAC considers that it would be unlikely that suppliers would withdraw from the New Zealand market as a result of this decision, given the significant value of the market for haemophilia treatments (even following the savings achieved via this decision).

Pfizer has advised that it will provide educational resources to support patients who are switched to Xyntha. PHARMAC will work alongside suppliers and other stakeholders (including the Haemophilia Foundation) to ensure patients and clinicians are well supported.

Some clinicians considered that PHARMAC did not consult early and widely enough on this proposal. Detailed discussions should have involved a wider group of clinicians, not just a select group of clinicians from the Haematology Subcommittee.

PHARMAC took steps to consult with the NHMG and HTG early on in the process, beginning in November 2014, and prior to PHARMAC issuing the RFP in February 2015. We continued to provide regular updates on our progress and thinking at the quarterly NHMG and HTG meetings, seeking and considering the views of these groups when developing the proposal.

Due to the commercial sensitivity of certain aspects of the RFP, PHARMAC was only able to involve members of the Haematology Subcommittee in the evaluation of RFP bids received. Those members who were involved in the detail of the proposal are senior clinicians who treat haemophilia.

They have been endorsed by their relevant professional body to provide clinical advice to PHARMAC on haematology issues, including haemophilia.

Some patients felt that the consultation period was too short for a change of this magnitude.

PHARMAC extended the consultation period for patients following this feedback.

Patients will understandably be nervous about such a change, especially given that some of them would have had previous negative experiences with the New Zealand health system where they contracted hepatitis C or HIV from contaminated blood products. There will also be a fear of developing inhibitors as a result of the brand switch which is a very significant side-effect and which has long-term consequences for a patient’s health.

Adequate resources need to be provided to support patients through this change including additional counselling time with clinicians, nurses, and social workers. Educational resources like patient leaflets, videos and product workshops would be helpful. There also needs to be consideration of additional funding for parties helping with this brand switch.

Noted. This feedback has been taken into consideration in PHARMAC’s implementation planning. Resources include:

• clinician information sheet
• patient information sheet
• a demonstration video for Xyntha administration, and
• information about Xyntha.

PHARMAC and Pfizer will work with clinicians to ensure that they have the information and resources they need to support patients who are changing brands.

PHARMAC will work closely with haemophilia treatment centres and the Haemophilia Foundation of New Zealand to help ensure that patients receive the support they need as they undergo this change.