COVID-19 antivirals: Decision on the role of molnupiravir in New Zealand’s treatments portfolio

Medicines COVID-19 Decision

What we’re doing

We have made the decision to retain funded access to molnupiravir (Lagevrio) for a small group of people who are unable to receive the preferred antivirals for the treatment of COVID-19, nirmatrelvir with ritonavir (Paxlovid) or remdesivir (Veklury). This means from 15 August 2023 molnupiravir will be available subject to its own set of access criteria.

These access criteria will stay in place while current stock of molnupiravir remains available and is not expired. We have not secured additional stock of molnupiravir as part of this decision (see below for further details).

Any changes to the original proposal?

This decision was subject to a consultation letter dated 4 April 2023 which sought feedback to clarify the role of molnupiravir in New Zealand’s portfolio of funded COVID-19 treatments. Feedback was sought on two options:

  • Stop funding molnupiravir and delist molnupiravir from the Pharmaceutical Schedule, meaning that it would no longer be publicly funded for the treatment of COVID-19 in New Zealand.
  • Amend the eligibility criteria for molnupiravir to limit funded access to a smaller group of people who may still be expected to benefit from treatment.

Specific questions were provided in the consultation to help guide the feedback submitted.

A wide range of stakeholders shared their perspectives and additional information, which has helped inform our decision regarding the availability of funded molnupiravir.

Based on the feedback received, we have decided to retain access to molnupiravir for the small group of people who are unable to receive the preferred antivirals.

Further information regarding the detail of this proposal is provided below.

Who we think will be most interested

  • People involved in the care and treatment of people with COVID-19
  • People (and their whānau/carers) at higher risk of experiencing severe COVID-19, eg older people, non-vaccinated, unwell from other health conditions/comorbidities, Māori, Pacific people, people with disabilities
  • People taking many or particular medicines which may interact with other funded COVID-19 antivirals
  • People with kidney failure
  • Prescribers of antiviral treatments for COVID-19
  • Suppliers of COVID-19 treatments
  • Clinicians and researchers evaluating the benefits of COVID-19 treatments available in New Zealand
  • Pharmacists providing antiviral treatments for COVID-19
  • People who responded to the molnupiravir consultation

Detail about this decision

The Access Criteria 

The following Access Criteria will apply to molnupiravir (Lagevrio) from 15 August 2023. These criteria are based on the current antiviral access criteria, with some additional requirements to consider other preferred treatment options (see criterion 4 and 5 below). Prescriptions must be endorsed by the prescriber confirming that the person meets the Access Criteria.

Access criteria – from any relevant practitioner.

Approvals are valid for people where the prescriber confirms the person meets the following criteria and has endorsed the prescription accordingly:

All of the following:

  1. Patient has confirmed (or probable) symptomatic COVID-19, or has symptoms consistent with COVID-19 and is a household contact of a positive case;
    AND
  2. Patient’s symptoms started within the last 5 days;
    AND
  3. Patient does not require supplemental oxygen#;
    AND
  4. Nirmatrelvir with ritonavir has been considered for the patient, including but not limited to using the Liverpool COVID-19 Drug Interaction Tracker(external link), and is unable to be used for clinical reasons;
    AND
  5. Remdesivir is unable to be accessed;
    AND 
  6. ANY of the following:
    1. Patient is immunocompromised* and not expected to reliably mount an adequate immune response to COVID-19 vaccination or SARS-CoV-2 infection, regardless of vaccination status; or
    2. Patient has Down syndrome; or
    3. Patient has sickle cell disease; or
    4. Patient has had a previous admission to Critical Care or High Dependency care directly as a result of COVID-19; or
    5. Patient is aged 65 years or over; or
    6. Patient is Māori or Pacific ethnicity AND aged 50 years or over; or
    7. Patient is aged 50 years or over AND has not completed a primary course^ of COVID-19 vaccination; or 
    8. Patient has any combination of three or more high risk medical conditions for severe illness from COVID-19 identified by the Ministry of Health**;
      AND
  7. Not to be used with other COVID-19 antiviral treatments.

              Notes:

              * As per Ministry of Health criteria(external link) of ‘severe immunocompromise’ for third primary dose of COVID-19 vaccine

              ** People with high risk medical conditions identified by the Ministry of Health(external link)

              ^ ‘Primary Course’ defined as receiving at least two courses of vaccination against COVID-19

              # Supplemental oxygen to maintain oxygen saturation >93% or at or above baseline for patients with chronic resting hypoxia

              These Access Criteria will stay in place while stock of molnupiravir remains available.

              Nirmatrelvir with ritonavir (Paxlovid) and remdesivir (Veklury)

              There are no changes to the access criteria for nirmatrelvir with ritonavir or remdesivir or the way these treatments are accessed because of this decision.

              Pharmac will soon release a public consultation on proposed changes to the access criteria for all COVID-19 antiviral treatments including molnupiravir, nirmatrelvir with ritonavir and remdesivir. 

              Accessing supply of molnupiravir 

              Access to molnupiravir will continue under the current arrangements. Prescribers must endorse prescriptions, confirming that the person meets the access criteria.

              The access criteria will be available on Pharmac’s website and linked to Health Pathways.

              Molnupiravir is supplied to pharmacies and Te Whatu Ora - Health New Zealand hospitals at no cost, as stock has been purchased directly by Pharmac. Available supply of molnupiravir was purchased from the previously separate COVID-19 budget allocated by the Government. Funding for COVID-19 treatments and vaccines is now part of the Combined Pharmaceutical Budget (CPB).

              Molnupiravir will continue to be listed in Section B and Part II Section H of the Pharmaceutical Schedule. Molnupiravir is available to order by community pharmacies and Te Whatu Ora hospitals. This process is being managed by Te Whatu Ora. More information is available on the Te Whatu Ora website(external link).

              Supply to community pharmacies is managed through one wholesaler, ProPharma, and Te Whatu Ora hospitals can order from OneLink as required.

              The XPharm rule applies to these treatments in the community which means community pharmacies are not able to claim subsidy through usual claiming systems as Pharmac has purchased these medicines directly.

              Pharmacies will be reimbursed for their services by COVID-19 Care in the Community funding through Te Whatu Ora. Information regarding the claiming mechanism for this payment to pharmacies will be available from Te Whatu Ora. 

              Remaining stock of molnupiravir

              As of 24 July 2023, around 12,500 courses of molnupiravir remain available at the wholesaler and 8,800 courses in community pharmacies. This stock has expiry dates between January and May 2024.

              The Manatū Hauora COVID-19 Therapeutic Technical Advisory Group (CT-TAG) published a position statement on 28 February 2023 with its reasons why it recommended not to use molnupiravir as treatment in non-hospitalised patients with COVID-19.

              Clinical guidance from Te Whatu Ora for the treatment of COVID-19 was subsequently updated to reflect this position statement and also recommend against the use of molnupiravir in the treatment of COVID-19.

              Manatū Hauora COVID-19 (CT-TAG) Position statement on the use of molnupiravir(external link)

              We have also received advice from our COVID-19 Treatments Advisory Group regarding molnupiravir on a number of occasions. Most recently molnupiravir was discussed in February 2023 [PDF, 335 KB] and May 2023, where the Advisory Group recommended that, based on the evidence available, molnupiravir should not be funded for the treatment of COVID-19 in New Zealand. Advice from the COVID-19 Treatments Advisory Group regarding COVID-19 antivirals, including molnupiravir has recently been published on Pharmac’s website. The May 2023 records will be available soon.

              Since the release of the position statement, changes in clinical guidance, and advice from the COVID-19 Treatments Advisory Group, the use of molnupiravir has declined significantly to approximately 2% of oral antiviral dispensing in New Zealand.

              Based on data available to Pharmac, it appears that the people continuing to receive molnupiravir are elderly (aged over 80+ years) and the majority are New Zealand European. This group of people are likely to have a number of comorbidities and take multiple medicines, which means nirmatrelvir with ritonavir may be unsuitable and remdesivir may be impractical as it is not widely available in the community.

              We acknowledge the advice from our COVID-19 Treatments Advisory Group, the Manatū Hauora COVID-19 TAG Position statement and clinical guidance recommending against the use of molnupiravir. We also note the feedback received in response to the consultation supporting the availability of molnupiravir and that the currently available evidence for molnupiravir is inconclusive. On balance of this information, we consider it is appropriate that this small group of people at high-risk continues to be able to access molnupiravir while stock remains available and is not expired.

              Any decision to secure additional supply of molnupiravir would be a separate decision to be made by Pharmac.

              Our response to what you told us

              We’re grateful for the time people took to respond to the 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 below. 

              Theme

              Pharmac Comment

              Stop funding molnupiravir – lack of evidence of benefit

              Recommendations that the funding of molnupiravir be stopped based on recently published randomised controlled trials that raised questions about the efficacy of molnupiravir in the treatment of COVID-19.

              We acknowledge the efforts of the Manatū Hauora COVID-19 Therapeutic Technical Advisory Group and Te Whatu Ora in promoting the effective use of antiviral treatments and are pleased eligible people with COVID-19 are accessing treatments with the greatest evidence of benefit.

              We also note the February(external link) and May 2023 (currently unpublished) advice from Pharmac’s COVID-19 Treatment Advisory Group which supported the funding of molnupiravir being stopped based on the available evidence.

              Evidence for the use of molnupiravir continues to emerge and is not conclusive.

              We are aware of published evidence from the PANORAMIC trial (Butler et al; PANORAMIC Trial Collaborative Group. Lancet. 2023;401:281-93(external link)) in what was a largely vaccinated population during the Omicron variant era, which suggests that molnupiravir may not be effective in reducing the risk of hospitalisation or death as a result of COVID-19 infection.

              A number of observational studies, that include Australia (Van Heer & Majumdar. Lancet Preprint, 3 July 2023(external link)) and New Zealand, suggest that there may be benefit for some people from the use of molnupiravir.

              On balance, we consider it is appropriate to have molnupiravir available for a small group of people at high-risk. Pharmac is closely monitoring evidence for the efficacy of COVID-19 treatments and will continue to review the access criteria for molnupiravir as needed.

              Stop funding molnupiravir – risk of inappropriate prescribing

              Concern that the ongoing availability of molnupiravir could lead to increased inequities in access to appropriate medicines if it is seen as an easier option for people with complex health needs.

              Since the implementation of updated clinical guidance regarding the use of oral antiviral treatments, the use of molnupiravir has declined to approximately 2% of oral antiviral dispensing for COVID-19.

              The intention is not to increase the dispensing of molnupiravir; however, we acknowledge the concern that molnupiravir may be seen as an easier option for many people at high risk of severe illness or death as a result of COVID-19 infection.

              Based on the data that we have available it appears that the people who are receiving molnupiravir are generally a small group of older people aged 80 years and over of New Zealand European ethnicity. We will continue to monitor the use of molnupiravir for any changes.

              Continued funding of molnupiravir – high risk people

              Support for ongoing access to molnupiravir for the small group of people who cannot receive the other funded antivirals.

              We appreciate the information provided regarding people who would be expected to benefit from ongoing availability of molnupiravir. This feedback included observational evidence from NZ clinical practice.

              We note the concern raised that the delisting of molnupiravir could result in inequitable health outcomes for people who are not able to receive other treatments.

              We recognise the limitations of the PANORAMIC trial(external link) and its relevance to New Zealand, particularly the age of the study population. Clinical conditions that may mean other COVID-19 treatments are unsuitable increase with age, eg impaired kidneys or an increased number of medicines interactions. We note that PANORAMIC participants were much younger than users of molnupiravir in New Zealand (median age of 56.6 years, with 6% aged 75+ years. In New Zealand (to February 2023) the median age of people using molnupiravir was 71.2 years, with 45% aged 75+ years).

              The uncertainty regarding the efficacy of molnupiravir has been reflected in the access criteria. It is intended that the ongoing availability of molnupiravir is for high-risk people who are unable to receive nirmatrelvir with ritonavir for clinical reasons and where remdesivir is unable to be accessed.

              Continued funding of molnupiravir – inconclusive evidence

              Respondents supported the ongoing availability of molnupiravir in New Zealand and considered that the currently available evidence for the effectiveness of molnupiravir in the treatment of COVID-19 is conflicting.

              On balance of the available evidence and the feedback received in response to consultation, we consider there may be benefit in molnupiravir continuing to be available for a small group of high-risk people who are unable to receive other treatments for COVID-19.

              We will continue to review evidence regarding the efficacy of molnupiravir and its use in New Zealand to make changes to access as needed in future.

              Continued funding of molnupiravir – New Zealand specific data

              A preliminary retrospective observational analysis has been undertaken by Te Pou Hauora Tūmatanui - the Public Health Agency. Data suggest that molnupiravir may have a significantly protective effect against mortality in New Zealand, particularly for older people.

              Te Pou Hauora Tūmatanui’s preliminary analysis has been considered as part of Pharmac’s decision.

              Similarly, other recent retrospective observational analysis from Victoria, Australia (Van Heer & Majumdar. 2023(external link)) for people aged 70 years and over has indicated significant associations between treatment with molnupiravir and reductions hospitalisation or death. This was in a health setting similar to New Zealand’s, during the Omicron variant era in a largely vaccinated population, and the median age of molnupiravir users in the study was 77-78 years, broadly similar to New Zealand’s median age of 71.2 years. Treatment with molnupiravir was associated with a 55% (odds ratio (OR) 0.46, 95% confidence interval (CI) 0.39-0.53) reduction in the risk of COVID-19-associated death and 29% (OR 0.71, 95% CI 0.58-0.87) reduction in COVID-19-associated hospitalisation.

              Pharmac acknowledges however the limitations posed by many generic inherent biases common to observational analyses.

              Continued funding of molnupiravir – personal experience

              People shared their experiences of molnupiravir and the benefit it has provided them or the people they know.

              We would like to thank people for sharing their experiences with molnupiravir.

              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.