Decision on access criteria for tixagevimab with cilgavimab (Evusheld) for COVID-19

What we’re doing

We're pleased to confirm the access criteria for tixagevimab with cilgavimab, supplied under the brand name Evusheld, for the pre-exposure prophylaxis of COVID-19. Pre-exposure prophylaxis is when people who have not caught COVID-19 but are at severe risk, take medicine ahead of time to prevent COVID-19 infection. 

Tixagevimab with cilgavimab will initially be available through Te Whatu Ora – Health New Zealand hospitals for people who are severely immunocompromised and are not expected to mount an adequate immune response to COVID-19 vaccination or SARS-CoV-2 infection and are at risk of severe illness from COVID-19 infection. 

Medsafe has recently granted provisional approval(external link) to tixagevimab with cilgavimab for use in New Zealand and supply is now available. Access criteria will apply from 25 August 2022. 

We expect to extend access to primary care providers in the community from mid-September 2022, subject to the same access criteria. Further detail about how this will work will be provided closer to the time. 

In addition, from 25 August 2022 relevant COVID-19 treatments including tixagevimab with cilgavimab can be used in Te Whatu Ora hospitals for the treatment of people with persistent SARS-CoV-2 infection (unapproved indication), subject to access criteria.

Who we think will be most interested

  • People who are immunocompromised and their whānau
  • People who have persistent SARS-CoV-2 infection and their whānau
  • Healthcare professionals involved in the care of people with COVID-19 or at risk of severe illness from COVID-19
  • Pharmacies, Te Whatu Ora, Te Whatu Ora hospitals and pharmaceutical suppliers 

Tixagevimab with cilgavimab

What does this mean for people?

From 25 August 2022, people who are severely immunocompromised and are not expected to mount an adequate immune response to COVID-19 vaccination or SARS-CoV-2 infection at risk of severe illness from COVID-19, will be able to access tixagevimab with cilgavimab from Te Whatu Ora hospitals for the pre-exposure prophylaxis of COVID-19. 

What does this mean for Māori and Pacific peoples?

Available data for the COVID-19 pandemic in New Zealand tells us that people of Māori or Pacific ethnicity are at greater risk of severe illness and poor outcomes from COVID-19 infection. This means it is important for clinicians in Te Whatu Ora Hospitals to identify and provide treatment to eligible Māori and Pacific peoples. 

Any changes to the original proposal?

Possible change to recommended dose for tixagevimab with cilgavimab

This decision was subject to a consultation letter dated 14 June 2022. 

In the June 2022 consultation we indicated that Pharmac has secured supply of 20,000 courses of tixagevimab with cilgavimab (300mg) with an option to purchase an additional 20,000 courses if required. 

Following the June 2022 consultation we received information from the supplier of tixagevimab with cilgavimab (AstraZeneca) that it intended to increase the recommended dose for tixagevimab with cilgavimab in the pre-exposure prophylaxis of COVID-19 from 300 mg (150 mg tixagevimab with 150 mg cilgavimab) to 600 mg (300 mg tixagevimab with 300 mg cilgavimab), with repeat dosing at 600 mg every six months. This increased dosing is being implemented by Astra Zeneca globally based on emerging evidence that tixagevimab with cilgavimab is less effective against currently circulating Omicron subvariants, including BA.5 which is currently dominant in New Zealand. 

Tixagevimab with cilgavimab is given as two separate and sequential intramuscular injections of tixagevimab and cilgavimab, injected into the gluteal muscle (one medicine injected into each buttock). 

Medsafe recently granted provisional approval(external link) to tixagevimab with cilgavimab for pre-exposure prophylaxis of COVID-19 at the 300mg dose (150 mg of tixagevimab and 150 mg of cilgavimab). The 600 mg dose of tixagevimab with cilgavimab is not approved by Medsafe. We understand that an application for this dose has been submitted for review. Increasing the dose of tixagevimab with cilgavimab would increase the volume of the intramuscular injections. 

In response to consultation feedback and considering the impact that a potential increased dose of tixagevimab with cilgavimab could have on the implementation and the number of people who could be treated with the courses we have secured, we have changed the access criteria to target the most severely immunocompromised New Zealanders. This includes: 

  • adding heart transplant recipients (any time) alongside lung transplant recipients in the criteria
  • greater clarification of solid organ transplant and stem cell transplant recipients eligible for treatment, including people receiving induction immunosuppression, treatment with mycophenolate and people treated for graft rejection in the past 12 months
  • greater targeting of people with blood cancers at highest risk
  • including people receiving regular intravenous or subcutaneous immunoglobulin treatment
  • including people with a history of previous persistent SARS-CoV-2 infection.

The access criteria allow for a maximum funded single dose of 600mg IM (300mg tixagevimab and 300 mg cilgavimab) for clinicians who choose to treat their patients at the higher 600 mg dose. This dose is currently unapproved and means it would need to be to be prescribed and used in accordance with section 25 of the Medicines Act 1981. You can read more about section 25 of the Medicines Act 1981(external link) on Medsafe's website. 

We acknowledge that many respondents asked for wider access to this treatment. This included various timeframes for patients receiving immunosuppressive treatments or transplants be extended from the timeframes proposed. Following information from AstraZeneca that it intends to increase the recommended dose for tixagevimab with cilgavimab, we have decided that at this time these changes could not be accommodated with the courses we have available.

Detail about this decision

The following access criteria will apply to tixagevimab with cilgavimab in Te Whatu Ora hospitals from 25 August for the pre-exposure prophylaxis of COVID-19 for people who are severely immunocompromised and at risk of severe illness from COVID-19.

Indication – Pre-exposure prophylaxis

Access criteria - Any relevant practitioner. 

Approvals are valid for patients where the prescribing clinician confirms the patient meets the following criteria and has endorsed the prescription accordingly: 

All of the following: 

Notes:

* potent B-cell or T-cell depleting therapy such as rituximab, obinutuzumab, ocrelizumab, bendamustine, fludarabine, cladribine, alemtuzumab, anti-thymocyte globulin, CamPath antibody treatment, anti-B-cell bispecific antibody, CAR T-cells or BiTE antibody treatment. 

Funded dosing:

  • Medsafe has provisionally approved Evusheld for pre-exposure prophylaxis at a dose of 300mg IM (150mg tixagevimab and 150mg cilgavimab).
  • Maximum funded single dose of 600mg IM (300mg tixagevimab and 300 mg cilgavimab) permitted. This dose is not approved by Medsafe.
  • Repeat dosing is not currently funded.

Courses of tixagevimab with cilgavimab available

Pharmac has secured supply of 20,000 300 mg courses of tixagevimab with cilgavimab. The agreement between Pharmac and AstraZeneca allows for an additional 20,000 300 mg courses to be ordered if required. 

Based on the proposed increased dose of 600 mg, we estimate the courses secured would be enough to treat approximately 10,000 people. This is significantly less than the 20,000 people we anticipated when we consulted in June 2022. It will be important for clinicians to target treatment to the most severely immunocompromised people at risk of severe disease from COVID-19 infection eligible for treatment. 

We continue to assess if additional courses would be secured and used to treat a wider group of people or re-dose people to provide extended protection. Any decision to secure additional courses would consider any new evidence and advice from our COVID-19 Treatments Advisory Group and be subject to a separate consultation and decision process. 

The first shipments of tixagevimab with cilgavimab have arrived in New Zealand and are available for ordering by Te Whatu Ora hospitals directly from Healthcare Logistics. Of the 20,000 300 mg courses of tixagevimab with cilgavimab that Pharmac has secured, 13,500 courses have arrived in New Zealand. Of these, approximately 12,400 courses are available for ordering by Te Whatu Ora Hospitals. This stock has an expiry date of 31 December 2022. 

An additional 6,500 300 mg courses are scheduled for delivery from September 2022. We expect these 6,500 courses will have extended expiry dates compared to currently available stock. 

Accessing supply of tixagevimab with cilgavimab

Like other COVID-19 treatments funded by Pharmac, tixagevimab with cilgavimab will not be accessed via a standard Special Authority. Instead, prescriptions must be endorsed by the prescriber confirming that the patient meets the Access Criteria. The Access Criteria will be available on Pharmac’s website(external link) and linked to Health Pathways. This approach allows us to easily make changes to the criteria if required in a timely way. 

Te Whatu Ora Hospitals 

From Thursday 25 August 2022 supply of tixagevimab with cilgavimab will be available to order by Te Whatu Ora hospitals, directly from Healthcare Logistics. To ensure the limited number of courses secured are available as widely as possible, Pharmac expects that stock will be ordered as required to support planned appointments or clinics for eligible people and Te Whatu Ora hospitals will not hold significant volumes of stock. 

Community Supply 

Tixagevimab with cilgavimab will not be immediately available in the community. Pharmac is working with Te Whatu Ora to make tixagevimab with cilgavimab available in the community. We anticipate this will be in place from mid-September 2022. We will provide further information closer to the time. 

Listing of tixagevimab with cilgavimab on the Pharmaceutical Schedule 

Tixagevimab with cilgavimab is listed in Section B and Part II Section H of the Pharmaceutical Schedule, at a price of $0 as it has been purchased directly by Pharmac. COVID-19 treatments are funded from a dedicated budget allocated by the Government. That means COVID-19 treatment costs do not come from the annual budget for New Zealand’s medicines (the Combined Pharmaceutical Budget). 

For more information about distribution and stock availability, please visit our main COVID-19 web page

Where to get more information 

For the most up to date information regarding all COVID-19 treatments – please check our website (external link) 

Persistent SARS-CoV-2 infection

What does this mean for people?

From 25 August 2022, people with persistent SARS-CoV-2 infection will have access to a range of COVID-19 treatments from New Zealand’s portfolio. 

We have heard from clinicians involved in the treatment of people with COVID-19 that there is a small number of people who are extremely immunocompromised who have persistent SARS-CoV-2 infection, who are unable to clear the virus and who remain unwell. 

The access criteria will provide clinicians treating people with persistent COVID-19 with access to New Zealand’s portfolio of COVID-19 treatments to use as appropriate for individual patients, via Te Whatu Ora hospitals. 

Any changes to the original proposal?

This decision was subject to a consultation letter dated 14 June 2022. 

We consulted on applying criteria for persistent SARS-CoV-2 infection to a number of currently funded treatments including casirivimab with imdevimab (supplied under the brand name Ronapreve). 

Current evidence indicates that casirivimab with imdevimab is not effective against the Omicron variant of COVID-19, including its current subvariants. We have decided that casirivimab with imdevimab will not be included as a funded treatment for persistent SARS-CoV-2 infection at this time. We will continue to evaluate evidence as it emerges. 

There have been no changes to this proposal because of the consultation feedback we received. Consultation feedback received has been summarised at the end of this notification letter. 

Detail about this decision

The following access criteria for persistent SARS-CoV-2 infection will be applied to nirmatrelvir with ritonavir, molnupiravir, remdesivir, and tixagevimab with cilgavimab in Te Whatu Ora hospitals from 25 August 2022. Prescriptions must be endorsed by the prescriber confirming that the patient meets the following Access Criteria: 

Initial Application – Treatment of persistent SARS-CoV-2 infection*

Access criteria - Any relevant practitioner 

Approvals are valid for patients where the prescribing clinician confirms the patient meets the following criteria and has endorsed the prescription accordingly 

All of the following:

  1. Patient has laboratory confirmed diagnosis of persistent SARS-CoV-2 infection (≥20 days); and
  2. Patient is immunocompromised; and
  3. A multidisciplinary team (including an infectious disease physician) considers the treatment plan to be appropriate. 

Note: Indications marked with * are unapproved indications.

Accessing supply of treatments for persistent SARS-CoV-2 infection

Access to currently funded treatments for persistent SARS-CoV-2 infection will continue under current arrangements. 

The use of COVID-19 treatments for persistent SARS-CoV-2 Infection is an unapproved indication. This means that when they are being used for the treatment of persistent SARS-CoV-2 infection, these medicines will need to be to be prescribed and used in accordance with section 25 of the Medicines Act 1981. This allows authorised prescribers to prescribe any medicine (approved or unapproved) for a particular patient in their care. You can read more about section 25 of the Medicines Act 1981, including the definition of authorised prescribers, on the Medsafe website(external link)

Due to the complexity of these cases, it is expected that people with persistent SARS-CoV-2 Infection will be managed from within DHB Hospitals by specialist multidisciplinary teams. 

Sotrovimab update

The June 2022 consultation on Access Criteria also included proposed criteria for sotrovimab (supplied under the brand name Xevudy) to treat people with COVID-19. We understand that sotrovimab is not approved by Medsafe for use in New Zealand and an application is currently under review. We will notify any decision on access criteria for sotrovimab separately.

Our response to what you told us

We’re really grateful for the time people took to respond to this consultation. 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 available on our notification webpage.  

Theme

Pharmac Comment

Support

Support for treatments being made available for immunocompromised patients at risk of severe COVID-19 infection.  

We are pleased to secure these treatments and to confirm Access Criteria which would make treatments available to people who are severely immunocompromised at risk of severe illness from COVID-19 infection and at risk of inadequate immune response to SARS-CoV-2 vaccination or infection.

Querying access for individual patients 

Individuals requested access to tixagevimab with cilgavimab and for specific circumstances including solid organ transplant (3.5 years ago), chronic kidney disease, myasthenia gravis, psoriatic arthritis in combination with immunosuppression.

We appreciate the time that people have taken to provide us with feedback and share their personal stories with us. Depending on the immunosuppressive treatments being received, people with these conditions may be eligible for treatment with tixagevimab with cilgavimab. Anyone who considers they may be eligible for treatment with tixagevimab with cilgavimab should seek advice from their specialist clinician. 

We acknowledge that not everyone who might benefit from treatment with tixagevimab with cilgavimab would be able to access it. The access criteria have been designed to target available treatment courses to people most at risk of an inadequate immune response and severe illness following COVID-19 infection.

  

Tixagevimab with cilgavimab Access Criteria

A respondent noted that criteria 2.1.1, 2.1.2, 2.1.3, 2.1.5, and 2.1.10, as proposed/numbered in the June consultation letter, could be amended to more specifically target profoundly immunocompromised people and reflect the current treatments available in New Zealand.

 

We have proposed changes to criteria 2.1 to clarify the targeted patient groups, including people that have received potent B-cell or T-cell depleting therapy using a range of treatments.

Changes to the criteria to include people receiving venetoclax (currently funded by Pharmac) and Bruton tyrosine kinase inhibitors, which are not currently funded but are available in New Zealand.

In responses to concerns that the criteria may be too broad, the criteria have been amended to clarify the groups of people with blood cancers who would be eligible for treatment with tixagevimab with cilgavimab.

Respondents requested the timeframes for those who have received B-cell or T-cell depleting therapy or those who have been transplanted for access to tixagevimab with cilgavimab should be extended beyond 12 months or removed.

Respondents also requested that access to tixagevimab with cilgavimab for lung transplant recipients (any time period) should also include heart transplant recipients. 

Respondents requested time-unlimited access be extended to all solid organ transplant recipients, particularly for induction (not maintenance) immunosuppression or mycophenolate maintenance or treated for rejection within the last 12 months. 

Considering the feedback received and the availability of stock following proposed increases to the recommended dosing for tixagevimab with cilgavimab, we have not removed the timeframes in the criteria.  

Access Criteria have been amended to reflect the risk that may be faced by individuals receiving transplant induction immunosuppressant treatment and those receiving maintenance immunosuppressant treatment. This includes mycophenolate mofetil, or those being treated for graft rejection within the past 12 months. Change reflects that the risk of severe COVID-19 for transplant recipients is related to the treatments being received rather than the time period since receiving an organ transplant. Heart transplant patients are also included.

Tixagevimab-cilgavimab should be made available to people who have not received COVID-19 vaccination and who are at high risk of progression to severe COVID-19. 

Respondents noted that this may offer benefits for Māori and Pacific patients who may be over-represented in the unvaccinated high-risk population.

As a result of the limited courses available we have not expanded access to include unvaccinated people who have not received vaccination against COVID-19. We consider there are other treatment options including vaccination and antiviral treatments that may be more appropriate in the first instance. 

The access criteria for tixagevimab with cilgavimab allows access for people who are considered at high risk of severe illness as a result of COVID-19 infection and are unable to be vaccinated against COVID-19 due to medical contraindication.

Access to tixagevimab with cilgavimab be available for early treatment for high-risk groups with confirmed (or highly suspected) SARS-CoV-2 infection, who are unable to receive nirmatrelvir with ritonavir.

We have not extended use of tixagevimab with cilgavimab for the treatment of individuals with COVID-19 infection at this time. We understand that a submission regarding this is expected to be made to Medsafe by AstraZeneca shortly. Available data for this indication will be reviewed at the August 2022 meeting of Pharmac’s COVID-19 Treatments Advisory Group. 

Requested that access to tixagevimab with cilgavimab pre-exposure prophylaxis also include people with a history of persistent SARS-CoV-2 infection.

We have amended the criteria to include individuals with a history of persistent COVID-19. This change reflects the risk faced by these people from future COVID-19 infection.

Access to tixagevimab with cilgavimab to include immunocompromised patients with no spike antibodies.

Noting the lack of equitable availability of serology testing in New Zealand and challenges associated with is interpretation, we have not specifically included in the criteria patients with no spike antibodies measured, rather we have identified conditions and treatments that may cause an individual to be profoundly immunocompromised.

Some rheumatology patients with life-threatening autoimmune conditions (such as systemic lupus erythematosus, dermatomyositis) will be on similar medications to patients with recent solid organ transplants.

We acknowledge that there may be a range of people, not explicitly identified in the criteria who are immunocompromised and at risk from COVID-19 infection.

Noting the limited courses available, the access criteria have been designed to target access to the most profoundly immunocompromised people. Based on the advice and feedback we received, this includes transplant patients who have received immunosuppression with a combination of agents.

We continue to welcome feedback and review the criteria as tixagevimab with imedivimab is implemented in New Zealand.

Pharmac’s exceptional circumstances framework would remain available for people where suitable funded treatments are not available for them. 

Identification of eligible patients for tixagevimab with cilgavimab

Primary care is not appropriately resourced to identify eligible patients and administer tixagevimab with cilgavimab and this should be the responsibility of secondary care specialists.

Initially tixagevimab with cilgavimab for the pre-exposure prophylaxis of COVID-19 will be available in Te Whatu Ora hospitals only.

Pharmac is working with Te Whatu Ora’s COVID-19 Care in the Community Team to establish appropriate access for tixagevimab with cilgavimab in the community to meet the needs of eligible people who do not receive regular care from Te Whatu Ora Hospitals and need access to treatment in their community.

Pharmacists are well placed to provide equitable access to these treatments and reduce pressure on general practice and hospitals and should be appropriately reimbursed for these services.

We acknowledge that Pharmacists may be well placed to support the administration of COVID-19 treatments in community settings. 

Tixagevimab with cilgavimab has been listed in Part II Section H and Section B of the Pharmaceutical Schedule, which would allow it to be administered in the community and hospitals, including by community pharmacists if required. 

Pharmac is working closely with Te Whatu Ora’s COVID-19 Care in the Community Team to establish appropriate access for tixagevimab with cilgavimab in the community. 

Te Whatu Ora’s COVID-19 Care in the Community team is responsible for establishing the fees for providing these treatments to patients, we will share this feedback with them.

Use of serology testing to identify eligible patients

One respondent provided feedback that serology testing may be helpful for identifying eligible patients for pre-exposure prophylaxis. 

Other feedback acknowledged that serology testing may not be available nationally and that there is no standard for interpreting results and the use of serology testing may contribute to additional burden on laboratory services and may also be a further barrier to accessing treatment in the highest risk groups.

We acknowledge that serology testing may be useful for the identification of profoundly immunocompromised patients however, on balance of the feedback provided and advice from serology experts, the difficulty in interpreting results and its possible contribution to inequitable access to these treatments we have not included it in the access criteria at this time. 

We note the review of COVID-19 serology in New Zealand by McAuliffe & Blackmore NZ Med J 2020(external link).

General

Māori and Pacific peoples are over-represented in those experiencing COVID-19 and making more treatments available will contribute to approved outcomes for these groups.

We are pleased to be able to make more COVID-19 treatments available to people who need them. It will be important for clinicians at Te Whatu Ora hospitals to identify eligible Māori and Pacific peoples. 

We are working with the Te Whatu Ora’s COVID-19 Care in the Community Team to ensure these treatments are accessible in the community to eligible Māori and Pacific peoples.

Raised that tixagevimab with cilgavimab may be less effective against the BA.4 and BA.5 Omicron subvariants.

Evidence for the effectiveness of COVID-19 treatments against new variants of COVID-19, including BA.4 and BA.5 continues to emerge. As this evidence becomes available, we continue to seek regular advice from our COVID-19 Treatments Advisory Group and make changes to the access criteria as needed. 

Updated Information provided to us by the supplier (AstraZeneca) indicates that it intends to increase the recommended dose for tixagevimab with cilgavimab to 600 mg, in part due to emerging evidence of reduced efficacy against the BA.4 and BA.5 variants of COVID-19. Use at this increased dose would be unapproved as the application remains under review with Medsafe.

Queried the returns policy for tixagevimab with cilgavimab in order to avoid wastage and redistribute stock if required

Pharmac has secured supply of 20,000 (300 mg) treatment courses of tixagevimab with cilgavimab. The first deliveries have arrived in New Zealand and have an expiry of December 2022, the remainder of this stock would have an expiry date of October 2023. As this stock has been secured and paid for by Pharmac it would not be able to be returned to AstraZeneca.

We understand that the Medicines Act 1981, does not currently allow for stock of pharmaceuticals to be shared between pharmacies. Noting the limited number of treatment courses available (10,000 at 600 mg) and the intent is prophylaxis prior to infection, we expect treatment would be scheduled and supply ordered for known people in advance, rather than large volumes being held for opportunistic dispensing.

Concerns were raised about the current workload and ongoing capacity of primary care to provide currently available COVID-19 treatments.

Concerns were also raised about the ability of patients to access these treatments with COVID-19 and influenza continuing to circulate in the community

We acknowledge that workloads across the health sector remain high due to the ongoing COVID-19 pandemic. 

We expect the prescribing of tixagevimab with cilgavimab would be a collaborative effort between Secondary and Primary Care. It is expected that Secondary Care Clinicians would lead the identification of eligible patients with Primary Care could provide support to administer treatments as needed.

Tixagevimab with cilgavimab and sotrovimab are specialist medicines and training modules should be available to pharmacists.

The supplier of tixagevimab with cilgavimab has developed resources and information that would be available to support the implementation of these treatments. In addition, information will also be made available via Health Pathways and the Hospital Guidelines for COVID-19 Treatments. Given the relatively small numbers of people who would receive treatment and their similarities to other currently available treatments Pharmac has not commissioned training modules specifically for these treatments. We will continue to monitor information and training needs of the sector, working closely with Te Whatu Ora.

Persistent SARS-CoV-2 infection Access Criteria

Respondents considered the proposed Access Criteria for the treatment of Persistent SARS-CoV-2 infection were appropriate.

We are pleased that the proposed Access Criteria are supported and that treatments would be available to New Zealanders with persistent SARS-CoV-2 infection where a multidisciplinary team considers this to be appropriate.

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 660 050.