Decision to fund risdiplam (Evrysdi) for spinal muscular atrophy

Medicines Decision

Pharmac will fund risdiplam for New Zealanders with spinal muscular atrophy (SMA) who meet eligibility criteria

What we’re doing

We're pleased to announce that from 1 May 2023, Pharmac will fund risdiplam, branded as Evrysdi, for New Zealanders with spinal muscular atrophy (SMA) who meet eligibility criteria. 

This means that there will be two funded options for the treatment of SMA in New Zealand with the same access criteria for symptomatic and pre-symptomatic SMA, providing a choice for people with SMA, their whānau or caregiver and treating clinician to determine the best treatment option:

  • Risdiplam is an oral treatment option that can be given or taken daily at home
  • Nusinersen, which has been funded since 1 January 2023, is given in hospital as an intrathecal injection into the spinal canal.

SMA is a rare disorder. We estimate that in the first year, 30 to 50 people will be eligible for funded treatment with either nusinersen or risdiplam. We expect that each year up to four additional people may be diagnosed with SMA and be eligible for treatment.

Risdiplam will be managed via a direct delivery programme managed by the supplier, Roche. Please see more details below.

Any changes to the original proposal?

This decision was subject to a consultation letter dated 19 January 2023.

No changes have been made to the access criteria for people with symptomatic SMA.

When we originally consulted, it was proposed that Pharmac would widen access to risdiplam to include pre-symptomatic use provided risdiplam was granted Medsafe approval for this use and Pharmac received a positive funding recommendation from our clinical advisors.

We are pleased to confirm that these requirements have been met and risdiplam will be funded for pre-symptomatic use from 1 May 2023, with the same funding criteria as nusinersen.

We have heard that people would like wider access to SMA treatments, including for those who are aged over 18 years at the time they start treatment. We are currently assessing the use of SMA treatments in wider population groups and sought expert clinical advice from the Rare Disorders and Neurological Advisory Committees in March 2023.

The full record of the discussion will be available in the coming months and will be available on our Application Tracker.(external link)

The next step will involve assessing and ranking a proposal to widen access to SMA treatments.

Who we think will be most interested

  • People with SMA, their whānau, friends, and caregivers
  • Healthcare professionals involved in the care of people with SMA
  • Te Whatu Ora – Health New Zealand hospitals and other organisations who deliver services and support for people, and their whānau who are affected by SMA
  • People or groups with an interest in treatments for rare disorders
  • Pharmacies and wholesalers
  • Pharmaceutical suppliers

Detail about this decision

Risdiplam will be listed in Section B and Part II of Section H of the Pharmaceutical Schedule from 1 May 2023 as follows:

Chemical

Formulation

Brand

Pack size

Price and subsidy

Risdiplam

Powder for oral soln, 750 mcg per ml, 60 mg per bottle

Evrysdi

80 ml OP

$14,100.00

A confidential rebate will apply that will reduce the net price of risdiplam. The Evrysdi brand will have protection from delisting and subsidy reduction until 30 June 2026.

Risdiplam will be funded subject to the following Special Authority criteria (the same as nusinersen):

Special Authority for Subsidy

Initial application – (spinal muscular atrophy (SMA)) from any relevant practitioner. Approvals valid for 12 months for applications meeting the following criteria:

All of the following:

  1. Patient has genetic documentation of homozygous SMN1 gene deletion, homozygous SMN1 point mutation, or compound heterozygous mutation; and
  2. Patient is 18 years of age or under; and
  3. Either:
    1. Patient has experienced the defined signs and symptoms of SMA type I, II or IIIa prior to three years of age; or
    2. Both:
      1. Patient is pre-symptomatic; and
      2. Patient has three or less copies of SMN2

Renewal – (spinal muscular atrophy (SMA)) from any relevant practitioner. Approvals valid for 12 months for applications meeting the following criteria:

All of the following:

  1. There has been demonstrated maintenance of motor milestone function since treatment initiation; and
  2. Patient does not require invasive permanent ventilation (at least 16 hours per day) in the absence of a potentially reversible cause while being treated with risdiplam; and

Risdiplam not to be administered in combination other SMA disease modifying treatments or gene therapy.

Similar restrictions will apply in Part II of Section H of the Pharmaceutical Schedule.

Risdiplam will be listed with the “Xpharm” restriction. More detail on this is provided below.

Direct delivery of risdiplam

People taking risdiplam will be able to access their medicine at an agreed nominated collection point – this could be a community pharmacy, a Te Whatu Ora hospital or, if necessary, an alternative location that has a refrigerator and can safely store the medicine. In some cases, direct delivery may be possible to a person’s home after dispensing. You will be able to confirm your risdiplam collection point with the dispensing pharmacy.

Roche, the supplier of risdiplam, will be responsible for managing a direct delivery programme of risdiplam. We have agreed this approach with the supplier to help remove access barriers for people with SMA and their whānau, to help manage the supply of a small volume product that requires some additional precautions to prepare, and to reduce the financial impact, risks and costs for community pharmacies and through the distribution chain.

The direct delivery process will include the following steps:

  • there will be one or more central dispensing pharmacies that will manage the supply for all eligible people across the country
  • the central dispensing pharmacy will dispense supply monthly and reconstitute the medicine into a liquid so it is ready to use
  • prescribers will send prescriptions to a central dispensing pharmacy for processing
  • the pharmacy will then contact the person/caregiver to confirm the delivery location if this has not yet been arranged
  • once dispensed, supply will be delivered to the nominated collection point each month for the person or a caregiver or someone from their whānau to collect
  • the medicine should be stored in a refrigerator at the location where the person will receive their daily medicine
  • Roche will manage service payments to the central dispensing pharmacies and the nominated collection points.

Risdiplam will be listed in the schedule with the “Xpharm” restriction. An Xpharm listing means that community pharmacies cannot claim subsidy because Pharmac has made alternate distribution arrangements. A note in the schedule listing will refer to where you can find more information.

Note: the supply of risdiplam is via Pharmac’s approved direct distribution supply.
Further details can be found on the Risdiplam page.

Information will be available  from 1 May 2023 at the link above to guide prescribers and pharmacies how to access risdiplam supplies. 

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, are available in the table below. 

Theme

Comment

Support to fund risdiplam

Strong support for the funding of risdiplam, including:

  • Risdiplam is a highly effective treatment, considered equivalent in efficacy to nusinersen
  • It has the key advantage of oral delivery, which can be taken at home. This overcomes barriers to access posed by geographical location, cultural beliefs, and medical comorbidities such as significant respiratory disease or scoliosis which can make intrathecal administration difficult
  • Provides families/ whānau choice based on their needs
  • Great to have an alternative treatment that is less invasive
  • Reduced costs from administration of nusinersen to the healthcare system
  • Provides the option for families who moved overseas to access risdiplam to come back to New Zealand
  • Access to a self-administered medicine is important, further emphasised by recent natural disasters and isolation of many communities around New Zealand.

We are grateful to everyone who shared their experiences and those of their whānau with SMA and what treatment would mean to them. This feedback is in line with the clinical advice we have received and what we have heard from the health sector.

Pharmac is pleased to be progressing another proposal with the potential to substantially improve the health outcomes of New Zealanders with SMA.

Support for access to risdiplam in the pre-symptomatic setting. Noted that the FDA includes use in infants under two months of age. There is strong evidence that early and pre-symptomatic treatment, prior to motor neuron loss, achieves the best clinical outcomes.

We agree that treatment in the pre-symptomatic setting offers the best outcomes for people with SMA and are pleased we have been able to come to this decision now.

Since we consulted, we made changes to the proposal to include the funding of risdiplam in the pre-symptomatic setting from 1 May 2023.

Medsafe has recently approved risdiplam use in infants under 2 months of age, enabling the use of risdiplam in the pre-symptomatic setting. We expect this to be updated in the manufacturer’s datasheet before 1 May 2023.

Risdiplam in the pre-symptomatic setting was considered at a joint meeting by the Rare Disorders Advisory Committee and the Neurological Advisory Committee in March 2023. The Committees recommended funding of risdiplam in the pre-symptomatic setting with the same criteria as nusinersen with a high priority.

The record of this meeting will be available in the coming months on the Application Tracker.(external link)

Amendments to eligibility criteria

Requests to extend the criteria to include children with type 3b SMA or remove reference to SMA type. Responders noted:

  • The definition of type 3a vs 3b is somewhat arbitrary, and not used widely around the world. It is not always possible to precisely define onset of symptoms. 
  • Geographic, ethnic, and socio-economic factors could result in delayed recognition of symptoms and pose barriers to early diagnosis
  • There are only a very small number of children diagnosed with SMA3b
  • In the future, with a pre-symptomatic treatment programme, SMN2 copy number will not reliably distinguish SMA 3a from SMA 3b at the time of pre-symptomatic diagnosis
  • Children who present late to health services may do so – not just because their SMA is less severe - but also if they have restricted access to healthcare. This criterion will disadvantage children from rural areas and (as has recently been shown in the role out of COVID vaccine) Māori and Pacific children. This criterion, will widen the health inequity experienced by Māori.

We understand there is a strong desire to have a treatment available for all people with SMA, including starting treatment for people with different types of SMA that are currently excluded from the proposed criteria.

Progression of this proposal does not mean that we won’t widen access in the future. We have not expanded access at this time as we need to complete our assessment of wider access to SMA treatments to understand the impacts of treatment in these groups and to the health sector.

We sought further advice regarding initiation of nusinersen and risdiplam in people over 18 years old, or those diagnosed with other types of SMA at our recent joint Rare Disorders and Neurological Advisory Committees meeting in March 2023. Records of this advice will be available in the coming months and available on the Application Tracker. The next steps will involve assessing and ranking a proposal to widen access to SMA treatments.

We acknowledge that some individuals with SMA may experience delay in access to health services and diagnosis. For an individual that the treating clinician considers has experienced a delay in diagnosis or access to health care (for example someone is not identified as symptomatic prior to the age of 3 years as required in the criteria) and would meet the intent of the eligible population, we would be happy to consider a Special Authority waiver application, as meeting the intent of the access criteria.

Details on how to submit a Special Authority waiver application are available on our website.

We will also consider a Special Authority waiver application for nusinersen or risdiplam for any person with SMA that may have turned 19 years of age between the time of consultation on the nusinersen proposal in late September and the 1 January 2023 list date and is no longer eligible for treatment.

Consider funding SMA treatments for people initiating treatment as adults

  • Considered that it was discriminatory to not fund treatment for people initiating as adults
  • It would substantially benefit whānau and the wider community as people could continue to be involved in society and care for whānau etc
  • There is a cost to the system for adults with SMA, eg. cost of carers and treatment for falls etc
  • Suggestion that the number of adults with SMA is low
  • Described the impact of SMA as an adult on the individual and their whānau
  • No one with SMA should be left behind
  • Pharmac should seek advice from those with lived experience with SMA and relevant clinicians who treat adults with SMA
  • Unmet needs and challenges for adults with SMA differ to children, but are no less important
  • Adults with SMA have a long-term need for ongoing health support, eg. with a physiotherapist. These needs are currently not being met as specialist care has extremely long wait lists and the Primary Healthcare system has very few General Practitioners or Physiotherapists who have knowledge of the disease
  • It should be a priority to keep adults mobile or as mobile as possible this can only be happen with treatment

We understand there is a strong desire to have a treatment available for all people with SMA, including starting treatment in people who are over 18 years old that are currently excluded from the proposed criteria.

Progression of this proposal does not mean that we won’t widen access in the future. We have not expanded access at this time as we need to complete our assessment of wider access to SMA treatments to understand the impacts of treatment in these groups and to the health sector.

We have now sought further advice regarding starting nusinersen and risdiplam in people over 18 years old, or those diagnosed with other types of SMA at our recent joint Rare Disorders and Neurological Advisory Committees meeting in March 2023. As part of this meeting, a person with SMA and a treating clinician shared their lived experience of SMA in adulthood with our advisors to help inform the discussion.

The record of this meeting will be available in the coming months and will be available on our website here. 

 

Applications for initial Special Authority should be made by, or on discussion with, a neurologist. Given the high cost of SMA medicines, specialist knowledge required to determine which medication is best suited to any child, and to ensure that children access multidisciplinary specialist supports to ensure the best clinical outcomes. It was noted that this suggestion was also made for the nusinersen criteria, however was not adopted.   

We consider that restrictions within eligibility criteria should be used for funding purposes to help target treatment to people based on clinical characteristics rather than to provide clinical guidance.

As was the case for nusinersen, we expect that risdiplam would only be managed and prescribed by specialist neurologists. We do not consider it is necessary to include this limitation in the risdiplam funding eligibility criteria.

A response requested the renewal criteria be changed to remove the first renewal criterion as it is problematic due to interpretation, access to specialist physiotherapists to carry out the necessary motor function measures, ambiguity in the interpretation of such measures, and an international lack of consensus of meaningful measures, especially in older patients.

The responder considered that the second renewal criterion is reasonable and should be the only criteria for renewal.

We made changes to the renewal criteria as part of the nusinersen decision. The criteria for risdiplam align with these.

We appreciate this feedback and support removing any barriers that could occur as a result of the renewal criteria for the ongoing assessment of people with SMA receiving nusinersen or risdiplam. Recent clinical advice for the use of risdiplam for SMA removed the specific tests previously recommended and suggested more general wording to avoid access issues. We consider it is appropriate to retain some assessment of clinical benefit and the renewal criteria remain appropriate and enable clinician discretion. No further changes have been made.

Direct delivery programme

Support for direct delivery programme as it will help to overcome barriers to access and removes risk for community pharmacies handling high-cost medicine.

We appreciate this feedback and support removing any barriers that may negatively impact a person’s access to treatment.

Different preferences for delivery location were expressed:

  • Delivery at a nominated collection point is likely safer than delivery to a home address where cold chain could be broken if someone is not at home to receive the delivery
  • It would be preferable to have delivery options depending on personal circumstance – either direct to home or a local location
  • Process needs to be supportive, flexible and responsive to the needs of the person and their whānau
  • Need to provide face to face caregiver education regarding administration and storage, especially on first dispensing and when dose changes
  • Te Whatu Ora hospital pharmacy dispensing must also be possible and claimable to ensure continued supply for inpatients
  • Some responses considered community pharmacy dispensing is preferable for patients and health professionals, patient’s benefit from having the dispensing close to home, HPs benefit from visible dispensing records (shared electronic patient records)
  • In Australia, prescriptions can be dispensed from community pharmacy and this is easy, considered that it would also be appropriate to pick up from a local hospital.

Roche, the supplier of risdiplam, will be responsible for managing the direct delivery programme. We have provided this feedback to Roche to inform the development of the programme and supporting resources.

The direct delivery programme will include a process for a person or whānau to nominate their delivery location – being a community pharmacy, hospital pharmacy or if necessary an alternative location that has a fridge and can safely store the medicine until collection.  In some cases, direct delivery may be possible to a person’s home after dispensing.

We have been advised that caregiver education by a pharmacist regarding administration and storage is part of Roche’s direct delivery programme and will be coordinated by the central dispensing pharmacies.

Information will be available on the Pharmac website to guide prescribers and pharmacies how to access risdiplam supplies.  

Pharmac staff are working with Roche and treating clinicians to finalise the approach before the 1 May 2023 start date.

Some concerns were raised regarding the protective facilities and equipment that may be needed to prepare the oral solution based on the instructions in the Manufacturer’s datasheet. Recommend gloves, mask, eye goggles and good air flow/ space for preparing this medicine. It is unclear if this has been considered for implementation. Some pharmacies potentially won’t be able to do this and it would create a risk to their employees.

We have shared this feedback with the supplier, Roche, who will confirm expectations about the precautions necessary to prepare this medicine directly with any pharmacies involved in its direct delivery programme.

The confirmed distribution approach removes the need for community pharmacies to use protective equipment and facilities required to safely prepare the liquid as per the manufacturer’s instructions. We understand that most community pharmacies and some hospital pharmacies do not have access to facilities to prepare products requiring additional protective precautions.

A suggestion that reminders to whānau and prescribers would be helpful to maintain regular supply and valid prescription.

We have shared this feedback with the supplier, Roche, and understand that reminders will form part of the direct delivery programme and will be coordinated by the central dispensing pharmacies.

There needs to be a robust remuneration pathway for pharmacies in place for risdiplam, similar to the provisions to the COVID-19 care in the community agreements for the dispensing of oral antivirals before distribution begins. 

Welcome provisions for information and reference material that pharmacists can pass onto patients or practitioners.

 

The COVID-19 Care in the Community national funding was provided by Te Whatu Ora to support providing COVID-19 treatments to a potentially large number of people impacted by COVID-19. We do not expect this to be available for the supply of risdiplam.

We have shared this feedback with the supplier, Roche, so it is considered in the design of the direct delivery programme. Roche has confirmed there will be a payment mechanism to the nominated location to provide reimbursement for activities required such as receiving and storing the dispensed product, organising collection and providing face to face counselling with the first prescription. Roche will manage this directly with the pharmacies involved.

National screening

In addition to being supportive of newborn screening for SMA, pre-conception screening should be available for severe recessive disorders including SMA in New Zealand.

We have shared this feedback with our colleagues in Te Whatu Ora National Screening team.

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.