Decision to fund nusinersen (Spinraza) for spinal muscular atrophy

8 December 2022

Medicines Decision

What we're doing

We are pleased to announce that from 1 January 2023, Pharmac will fund nusinersen, branded as Spinraza, for New Zealanders with spinal muscular atrophy (SMA) who meet the eligibility criteria.

SMA is a rare genetic disorder which impacts infants through to adults and can cause disability and early death. Nusinersen will be the first funded treatment in New Zealand for people with SMA.

Through an agreement with the supplier of nusinersen, Biogen NZ Biopharma Ltd (Biogen), we will also be amending the pricing and exclusivity arrangements for three currently funded multiple sclerosis treatments. These products will remain funded with a change in the net price and protection from delisting and subsidy reduction until 30 June 2026.

Nusinersen for spinal muscular atrophy

What does this mean for people?

From 1 January 2023, people aged 18 years and under with pre-symptomatic SMA or symptomatic type I, II or IIIa SMA will be eligible to start funded treatment with nusinersen.

We estimate that in the first year, 30 to 50 people would be eligible for funded treatment with nusinersen. We expect that each year up to four people may be diagnosed with SMA and be eligible for treatment. As a result, the number of people receiving treatment is anticipated to increase over time.

Nusinersen is given as an intrathecal injection into the spinal canal and needs to be administered in hospital. We understand that Te Whatu Ora hospitals will need to establish or expand services to support the administration of nusinersen and this may take some time. Treatment is expected to be delivered through three main centres in New Zealand.

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

Any changes to the original proposal?

This decision was subject to a consultation letter dated 28 September 2022. You can read more about nusinersen and spinal muscular atrophy in the consultation letter.

We received lots of feedback which highlighted the great benefit this decision would have for people with SMA and their whānau. We’re really grateful to everyone who took the time to share their experiences with SMA, their support and for providing us with feedback.

We also received specific feedback about the access criteria and we have made some changes to the criteria to:

change the wording of the definition of SMA
change the pre-symptomatic criteria to include having three or less copies of the SMN2 gene, which means the criteria now include those people with pre-symptomatic SMA who have only one copy of the SMN2 gene
no longer refer in the renewal criteria to age-appropriate scales to assess motor milestone function, as this could create barriers to patient assessment
no longer refer in the renewal criteria to non-invasive permanent assisted ventilation
add clarification that nusinersen is not to be given in combination with other SMA disease modifying treatments or gene therapy, acknowledging that these non-funded treatments may be accessible to some people.

We also heard that people would like nusinersen funded for all people with SMA, including those who start treatment after 18 years old and other sub-types of SMA such as type IIIb. At this time, we have not extended access to nusinersen for these groups. We will be seeking further clinical advice for these additional groups in early 2023 once we have collected the relevant information. This decision does not mean we won’t make nusinersen available for more people in the future.

Detail about this decision

Nusinersen (Spinraza) will be listed in Section B and Part II of Section H of the Pharmaceutical Schedule from 1 January 2023, at the following prices and subsidies:

Chemical	Formulation	Brand	Pack size	Price and subsidy
Nusinersen	Inj 12 mg per 5 ml vial	Spinraza	1	$120,000.00

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

Nusinersen will be listed as a PCT-only pharmaceutical in Section B of the Pharmaceutical Schedule, meaning that only Te Whatu Ora hospitals will be able to make a subsidy claim.

Nusinersen will be listed in Section B and Part II of Section H subject to the following eligibility criteria (changes to the criteria following consultation are shown with additions in bold, deletions in strikethrough):

Special Authority for Subsidy/Hospital Indication restriction

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

All of the following:

Patient has genetic documentation of 5q SMA homozygous SMN1 gene deletion, homozygous SMN1 point mutation, or compound heterozygous mutation; and
Patient is 18 years of age or under; and
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 only two or three 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:

Both All of the following:

There has been demonstrated maintenance of motor milestone function (as assessed using age-appropriate scales) since treatment initiation; and
Patient does not require invasive permanent ventilation (≥ at least 16 hours per day), or non-invasive permanent (≥16 hours per day) assisted ventilation (breathing support administered via nasal cannula or face mask), in the absence of a potentially reversible cause while being treated with nusinersen; and
Nusinersen not to be administered in combination other SMA disease modifying treatments or gene therapy.

Changes to other pharmaceuticals associated with this decision

The supplier of nusinersen, Biogen, also supplies three treatments that are currently funded for people with relapsing remitting multiple sclerosis: natalizumab (Tysabri), dimethyl fumarate (Tecfidera) and interferon beta-1-alpha (Avonex).

As part of this proposal the net price for all three treatments will reduce by confidential rebate from 1 January 2023. They will all have protection from delisting and subsidy reduction until 30 June 2026.

There will be no changes to the current eligibility criteria or list price for natalizumab, dimethyl fumarate or interferon beta-1-alpha as part of this decision.

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 set out below.

Theme	Comment
*Support for the proposal to fund nusinersen*
Strong support for the proposal. In particular, we received supportive feedback regarding: Funding nusinersen would address an area of urgent unmet need The profound negative impacts of SMA on patients, whānau, and caregivers and the positive impact that nusinersen would have on their quality of life Funding nusinersen would give patients and their families hope Treatment with nusinersen would enable some parents and caregivers of those affected by SMA to remain employed and not have to provide around-the-clock care Nusinersen would enable families who were considering moving overseas for treatment to remain in New Zealand and retain their support networks, jobs, and stability	We are grateful to all the people who wrote in to tell us about their experiences or those of their whānau with SMA and what treatment would mean to them and their whānau. Pharmac is pleased to be progressing a proposal with the potential to improve the health outcomes of New Zealanders with SMA so substantially. This feedback is in line with the clinical advice we received and what we have heard from the wider health sector.
*Amendments to eligibility criteria*
Requests to remove/amend the age limits or types of SMA in the eligibility criteria, including: Expand access to those aged 19 years and over at the start of treatment Amend the criteria to include SMA types IIIb, IIIc, and those who become symptomatic after 3 years of age Remove the reference to ‘SMA type’ as it may disadvantage children who present late to health services	We understand there is a strong desire to have a treatment available for all people with SMA, including initiation of treatment in people over 18 years old, or different types of SMA that are excluded from the eligibility criteria. (More information about SMA types are explained in the consultation letter.) The eligibility criteria reflect the population requested in the funding application, the people identified by our clinical advisors as having the highest unmet health need and the most potential to benefit from treatment, and aligns with the clinical trial evidence that was considered by our clinical advisors. More information can be found in the Application Tracker record for nusinersen (for SMA types I II and III(external link) and pre-symptomatic SMA(external link)). We are not expanding access at this time as we need further clinical advice and analysis to understand the impacts of treatment in these groups and to the health sector. We welcome funding applications for the groups we haven’t yet considered, to help our future consideration of funding. Progression of this proposal does not mean that we won’t widen access in the future. We intend to seek further advice regarding starting nusinersen or risdiplam in people over 18 years old, or those diagnosed with other types of SMA, at our next Rare Disorders Advisory Committee meeting in March 2023. We understand that some individuals with SMA may experience delay in access to health services and diagnosis. For someone 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 three 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 any person with SMA that may have turned 19 years of age between the time of consultation in late September and the 1 January 2023 list date and is no longer eligible for treatment.
Requests that patients with one copy of the SMN2 gene should be included in the eligibility criteria. SMN2 copy number correlates with severity of disease, however it is not the only determinant of severity. If an infant with only one copy of SMN2 isn’t symptomatic at birth (ie. “pre-symptomatic”) it means they likely have less severe disease and could benefit from treatment.	We acknowledge that SMN2 copies are not a perfect prognostic biomarker, but it is the best phenotypic modifier of SMA identified to date. We agree that there may be some people with a single SMN2 copy that would develop type 1 or type 2 SMA, rather than type 0 (the most severe form) and would not be eligible for pre-symptomatic treatment under the criteria we consulted on. We have changed the criteria to include pre-symptomatic individuals with only one copy of SMN2.
Requests to restrict who can apply for the special authority for nusinersen to specialist neurologists who treat people with SMA. It was considered that this would not create unnecessary barriers and would be clinically appropriate.	We consider that restrictions within eligibility criteria should be used for funding purposes to help target treatment to patients based on clinical characteristics, rather than reflect the normal patient journey or provide clinical guidance. We expect that nusinersen will only be managed and prescribed by specialist neurologists in specific treatment centres that can administer treatment. However, we do not consider it is necessary to include this limitation in the nusinersen funding eligibility criteria.
Request to amend the definition of SMA in the eligibility criteria to “homozygous SMN1 gene deletion, homozygous SMN1 point mutation, or compound heterozygous mutation”	The criteria have been changed to reflect this wording.
Request to amend the renewal criterion 1 to remove the reference to how motor milestone function would be assessed (ie. scales), to reduce barriers to assessment.	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. We have removed the reference to ‘how’ motor milestone function should be assessed.
Request to amend renewal criterion 2, to align with the most recent Australia PBAC access criteria and to remove reference to non-invasive permanent ventilation. This was based on: the inclusion of non-invasive permanent ventilation as a stopping criterion for treatment does not align with clinical practice nusinersen has resulted in a change in the natural history of SMA disease, challenging clinicians to re-think thresholds for the use of respiratory support in SMA nusinersen-treated children with type 1 SMA may use many hours of non-invasive respiratory support, especially during infancy (related to increased hours of sleep), pre-school years, and over winter months with frequent intercurrent viral illnesses. These children continue to show good motor development, have good quality of life, and continue to derive clear benefits from nusinersen therapy	We appreciate the detailed feedback provided by experts who are treating people with SMA and acknowledge that Australia has amended its renewal criteria since we first assessed the application for nusinersen. We have changed the criteria to remove reference to non-invasive permanent ventilation. This means the NZ criteria regarding ventilation are the same as Australia’s. We do not consider this will materially change the appropriate use of nusinersen for those individuals who continue to benefit from treatment. We remain open to making further changes to the criteria as treatment and clinical practice evolves. We will also be sharing this feedback with our Rare Disorders Advisory Committee at their next meeting in March 2023.
Suggestion to review the criteria in three years in anticipation of increased international and Australian data on motor and respiratory outcomes.	We welcome this suggestion and are open to reviewing the eligibility criteria at any point based on updated evidence or a change in clinical practice.
Clear guidance is needed on whether a person can be treated with more than one disease modifying therapy for SMA. Whilst this proposal is about nusinersen, there are people in New Zealand on compassionate risdiplam therapy and there may be people moving to NZ from overseas after accessing other therapies. Suggest adding: “Nusinersen must not be administered in combination with gene therapy or risdiplam therapy”.	We welcome this feedback and have changed the criteria to include that nusinersen must not be administered in combination with gene therapy or risdiplam therapy. Although these treatments are not currently funded in New Zealand, it makes sense to include this as compassionate access is or may become available.
*Other agents - risdiplam*
Strong interest and requests that Pharmac consider funding risdiplam, an oral treatment for SMA. Risdiplam may be more suitable for some patients, such as when lumbar puncture is technically challenging Risdiplam may be more suitable for patients and families who have difficulty in travelling to or accessing the services required for nusinersen Treatment interruptions would be less likely with oral treatment A patient centred approach would enable patients to receive the correct treatment for their individual needs and circumstances. Oral treatment may be more acceptable to some populations. In other jurisdictions, approximately 1/4 to 1/3 of patients receiving nusinersen move to risdiplam when it is available.	We understand that risdiplam may be a more suitable treatment option for some people with SMA, particularly where there may be barriers to nusinersen treatment due to rural location, impact on whānau travelling, or clinical reasons that make intrathecal administration more challenging. An application for risdiplam for the treatment of symptomatic SMA has been assessed and is currently ranked on our Options for Investment List. An application for pre-symptomatic SMA was received in August 2022 and is under consideration. More information can be found on the Application Tracker(external link). Pharmac is in active discussions with the supplier of risdiplam, Roche, regarding the potential funding of risdiplam.
*Newborn screening*
Responses highlighted the need for a newborn screening programme for SMA but acknowledged that this is dependent on treatment being available, and that is unethical to screen without treatment options.	Pharmac has discussed the possibility of newborn screening programme with the National Screening Programme at Te Whatu Ora. We understand that for a screening programme to be rolled out, a funded treatment needs to be available. Pharmac continues to work with Te Whatu Ora to support the consideration of this service.

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.