UK nusinersen EAP for children with SMA Type 1 - Position statement from the North Star/ SMA-REACH UK Group

On 5th April 2017, the North Star / SMA-REACH UK group of seventy clinicians, physiotherapists, study coordinators, industry and advocacy groups’ representatives, including SMA Support UK, sent an open letter, signed on behalf of the group by Professor Francesco Muntoni, setting out their position and recommendations to the National Institute for Clinical Excellence (NICE), NHS England’s Care and Clinical Reference Groups (CRGs), NHS Trusts and Biogen.

You can read the letter and see the full list of the signatories here and read our explanation of the letter’s content below:

1. Current global status of nusinersen treatment for infants with Spinal Muscular Atrophy (SMA) Type 1  

For the first time, there is a treatment for this severe and extremely rapidly progressive disease. The group states clearly ‘we are no longer in a clinical equipoise position’ (‘equipoise’ is a state of genuine uncertainty on the part of the clinical investigator regarding the comparative therapeutic merits of each arm in a trial). In other words, clinicians are now certain of the merits of this treatment.

Nusinersen was licensed by the FDA in the USA on December 23rd 2016 for marketing as Spinraza for the treatment of SMA. A licensing decision from the European Medicines Authority (EMA) is imminent.  This will trigger whether the treatment will be referred and formally reviewed by NHS England and NICE.

In the meantime, Biogen’s EAP makes the nusinersen drug globally available free of charge to children with SMA Type 1, until such time as the drug is adopted by the local health systems.  

2. Current availability of the EAP in the UK compared to other European countries

After months of internal negotiations within their NHS Trusts, only 2 centres in England are able to offer the EAP (Newcastle and GOSH in London - the 2 centres originally involved in the Endear phase III clinical trial). Additional active UK Centres are: Belfast in Northern Ireland; Dundee in Scotland and Dublin in Eire. Together, these centres so far have treated 9 infants with SMA Type 1. This contrasts starkly with other EU countries such as Italy, where they are now close to treating 150 infants.

There is an increasing level of frustration from families, clinicians and the advocacy groups about the delays with the EAP in England.  Clinicians face the ethical dilemma of not being able to deliver a drug which is effective. They are seeing desperate families raising private funds and regularly travelling to France, Germany and Austria to access treatment promptly for their children. This is not acceptable and poses a significant risk to these fragile infants.

3. Obstacles to rapid and equitable access to nusinersen treatment via the EAP in the UK

3.1  The NHS England Clinical Reference Groups (CRGs)’s commissioning process and resource allocation

Nusinersen treatment is delivered by intrathecal (spinal) injection. This needs staff time, expertise and other resources. There is currently no clear mechanism for the national CRGs to commission (fund) these sorts of resources.  The system only allows resources to be allocated once a treatment has been formally reviewed by NHS England and NICE.  The timeline for this process can take years.

Centres that have been able to start the EAP with a small number of children, have had to identify internal resources to do this. Not surprisingly, due to the challenging financial situation of the NHS Trusts, this has been slow.

3.2  Prioritisation of local children

The lack of a clear national way to allocate resources for the programme has meant that Centres have had to use local criteria to decide which children should have priority. This has meant that only children in the care of the local hospital which has managed to activate the EAP have started treatment. This contrasts with the group’s desire to follow nationally agreed prioritisation criteria so that access to this effective drug is equitable and fair for all children in the UK.

3.3  Highly Specialised Technology (HST) assessment criteria by NICE

As SMA is a rare disease and numbers eligible to access the treatment will be relatively low, this group considers an HST assessment by NICE to be appropriate. However,  to be eligible for an HST assessment, treatment can usually be administered only in a small number of centres.  Although there is no specific number given, it is typically small, usually not more than a handful.

4. Seeking a way forward

Clinicians involved in the UK paediatric neuromuscular networks North Star and SMA REACH have, over the last few months, been talking with the individual NHS Trusts, the CRGS, NICE, Biogen and the advocacy groups to find ways to progress the EAP and open new sites.

4.1 Proposed national clinical guidelines for access

The group has now produced draft treatment guidelines on both inclusion and discontinuation criteria for the EAP. These are based on:

evidence from analysing the data from the Endear phase III trial
discussions with clinicians from other countries in which there is experience with the nusinersen EAP (US, Italy, Germany, Spain) about the criteria they are using
discussions with representatives of ethics committees both in the UK and overseas

These will potentially provide clinicians with guidelines that will lead to fair and equitable access to nusinersen across the country. 

4.2 Proposal for treatment delivery by all sites in the SMA-REACH UK clinical network

The group anticipates that, at the moment, some 100 infants would benefit from this drug.   However, due to capacity and lack of financial resources, it would be impossible for this treatment to be delivered by the  small number of centres required for an HST. Also it is not in the interests of a child’s health and well-being to travel when sick and weak. 

The group therefore considers it highly desirable that any centre involved in the clinical SMA-REACH UK clinical network that makes a request to deliver the EAP, should be able to do so for the children they care for. These are centres that have, with charity funding, worked as part of the network for more than ten years.  A similar and successful model is already working for children with Duchenne muscular dystrophy who receive the treatment Ataluren

The group strongly suggests that this development should not in any way prevent consideration of the treatment as an HST.

The group realises that this step will not immediately address the issue of national equity of access. Centres will inevitably be required to look after their local patients first. However, at the moment this is the only way to treat the largest number of children in the shortest period of time. Depriving children who can benefit from treatment only because a final national solution is complex and requires lengthy negotiations, seems unethical.

4.3 Proposal for a national priority registry

The group suggests that opening multiple sites would be a step towards the goal of setting up a national registry of children potentially eligible for treatment. The registry would be administered according to clinically set prioritisation criteria with central funding for locally delivered treatment. It would ultimately ensure fair and equitable access to the drug for children, no matter where they live in the UK.  

The advocacy groups support such a move and would be prepared to facilitate the setting up and administration of a national registry.

4.4 Proposed action for the CRGs

If the CRGs indicated now that such a national model would be the most likely future pathway for commissioning and resource allocation, they would provide a powerful tool that would help centres open swiftly, without months of internal Trust negotiations for resources.

Once the CRGs commissioning model has been finalised and they have given feedback, there could be a review of the number of treatment centres and the way the network is functioning.

5. Summary of the group’s request to NICE and the CRGs

The group realises that to achieve what is suggested above could take several months. With this position statement, it therefore asks for the following steps. That:

a. The NICE/ CRG assessment of the EAP and the allocation of resources to facilitate the opening of treatment sites is completed quickly
b. In the short term, centres that are part of the group’s clinical network and have expertise in dealing with children with SMA Type I should be able to offer the EAP
c. There should be no cap imposed on the number of treatment centres due to concern about the treatment’s eligibility for a potential HST assessment
d. The opening of multiple centres should not be used as a reason for declining the HST as an appropriate route for assessment
e. In the longer term, the group works with the CRGs and the advocacy groups to identify what system of networks / number of centres will best achieve equitable national access to this drug by children with SMA Type 1.


5th April 2017