Nusinersen had been tested with infants with SMA Type 1 in the clinical trial called ENDEAR. Newcastle and Great Ormond Street (GOSH) were UK clinical trial sites.

By Autumn 2016: the ENDEAR study results hadn’t been fully analysed and there was only limited knowledge about the efficacy of nusinersen across the full spectrum of infants and children with SMA Type 1. However, results had been sufficiently positive for Biogen to transition all children from the ENDEAR trial so that they could to continue to access nusinersen via extension studies.

This global Expanded Access Programme (EAP) was for children with SMA Type 1. Biogen would be providing the drug free of charge while countries assessed the drug and arranged for ‘reimbursement’ of the cost of the drug to Biogen to come from their own health care system. This was quite unprecedented.

The programme took a long time to set up in the UK which was why a significant number of families sought treatment in Europe due to the delays with getting the EAP up and running in the UK. The travel, financial commitment and general stress was enormous.

The reasons for the delays were due to NHS England’s Specialised Services not considering the evidence of the clinical effectiveness of the treatment to be sufficient, NHS Trusts not having funds to cover administration costs and NHS England’s concerns about providing these funds. Despite this, the programme started to roll out with the first children treated via the EAP in Spring 2017.

There was a huge amount of advocacy work by clinicians and Patient Groups throughout this time. As a result, on 4th July 2017 NHS England announced an interim policy that provided funds for administration costs for some children, but it took until 9th March 2018 to gain equitable access for all diagnosed with SMA Type 1 who could potentially benefit.

Anyone enrolled in the programme by November was assured of continued treatment unless the family and their clinician consider it appropriate to stop.

The programme closed in Scotland in May 2018 following the decision there for the Scottish NHS to fund treatment for infants with SMA Type 1.

Biogen closed the programme to new infants in England, Northern Ireland and Wales on 1st November 2018 despite the fact that NICE (England’s National Institute for Health and Care Excellence) was still engaged in appraising the treatment and had not made a final decision whether it would recommend it for funding by the NHS. Biogen representatives travelled to our office in Stratford to explain their positions. We made it clear that we considered it unethical to place children and families in this position strongly urged them not to use children and families take this step and following this, continued to advocate for an extension of the programme or a ‘bridging solution’ until such time as NICE made its final decision.

More than 80 children in the UK remained on the programme. Biogen advised this was the most for any country in the world and that they had reached the limit of their willingness to continue to support the NHS – due largely to their frustrations with the NICE appraisal process.

Biogen’s decision left infants newly diagnosed with SMA Type 1 with no access to treatment between November 2018 and May 2019 and families in the most devastating position.

Following the NICE access decision on 15th May 2019, Biogen committed to re-open the EAP for infants newly diagnosed with SMA Type 1 in England, Wales and Northern Ireland until the new guidance was finally published with NHS England then starting to take over funding completely from July 2019.

2016

14th December: Patient Groups (PAGs) SMA UK (Then SMA Support UK and The SMA Trust) and MDUK started regular meetings with Biogen to advocate for UK access. SMA UK’s report to the community included contact details for the coordinators at the potential EAP sites at GOSH and Newcastle.

16th September: GOSH and Newcastle informed the SMA Community that Biogen needed to ensure that the proposed EAP could take place in the UK according to UK laws and regulations. It was anticipated that the approval process would be likely to take several months. Because of the two Centres experience in administering Nusinersen clinical trials, initially only they sites could potentially be able to participate in the proposed EAP. However, the expectation was that other sites could also be opened in the future.

It was clear that there was an urgent need to agree how to prioritise the requests of families with infants with SMA Type 1 whose child could potentially be enrolled in the EAP for Nusinersen. With this in mind, the two Centres were in discussion with other European and US sites to agree on the most rational and equitable approach.

2017

30th October: Further letter from the clinical / PAG network to NHSE raising that the interim policy, which excluded children with SMA Type 1 who have 1 or 3 copy number of SMN2, raised both practical and significant ethical issues that clinicians on the ground face when delivering the optimal care for children.

29th September: NHSE responded to the appeal in a letter which talked about the possibility of making a further application to NHS England’s specialised commissioning clinical panel. However, it also said ‘NHS England tries to avoid duplication of work with NICE where the timings are suitable’. It confirmed NICE was working to decide whether to appraise nusinersen via its technology appraisal system but there were no clear timelines for a decision on this yet.

23rd August: Clinicians and PAGS appeal NHS interim commissioning policy for Nusinersen treatment for infants / children with spinal muscular atrophy Type 1 under the expanded access programme. The inclusion criteria restrict access only for those infants aged 7 months or under at entry, and only for those with 2 copies of the SMN2 gene.

4th August: NHS England announced an interim policy that provided new funding to cover all hospital costs for administering nusinersen to children with SMA Type 1 who were under 7 months of age and had 2 SMN2 copies.

18th July: At the All Party Parliamentary Group (APPG) organised by MDUK, representatives from NHS England, Biogen, GOSH, leading neuromuscular consultants, families and PAGs shared their experiences and views on the current provision of nusinersen in a Q&A discussion. Main points to come out were:

• NHS England were now considering the clinical evidence from the European Medicines Agency (EMA) Assessment Report and funding implications to see if there was any possibility of their supporting the EAP for eligible children with SMA Type 1 until such time as it is closed by Biogen.
• Biogen had given the green light to any centre that had applied to them to be part of the EAP.
• There were now some 25 children receiving treatment, with another 20 who wished to take part waiting to hear what their position was.
• A referral from the Health Minister for NICE to begin to assess nusinersen’s longer term / wider availability was expected in the next few weeks.

13th July: Following our request, Biogen updated the community to say that although nusinersen had been approved by EMA and countries were therefore beginning to agree to fund it themselves:

"…children enrolled in the Biogen UK EAP would remain in the free of charge programme until local reimbursement and access is established. In the event of a negative reimbursement decision or where a patient falls outside of the reimbursement criteria, Biogen is committed to ensuring the patients still have access to nusinersen. Biogen remains supportive of the ongoing efforts of members of the clinical and advocacy community who are actively addressing the EAP challenges already identified within individual hospitals. To this end, Biogen continues to receive and assess EAP applications from individual hospitals within the process already established. As of July 11th 2017, the EAP is active in 7 sites in England, 2 in Scotland and 1 in Northern Ireland. Additional sites have been approved but are not yet active."

6th June: NHS England called lead clinicians and centre service managers together. SMA UK’s Support Team Manager was also invited. Due to the election ‘purdah’ and the NHS England (NHSE) communications approval process, no one at the meeting was able to discuss what went on until 5th July 2017.

Many issues with which families were all too familiar were raised, actions were planned and, by July, underway. This included:

• a plan to address the access issues facing individual children who had been identified as potentially eligible for the EAP by services and SMA Support UK.
• completing work started to establish clinical prioritisation criteria for access to the programme. This would be based on criteria that had been developed and was being used in other countries.

It was reported that James Palmer (Specialised Services Medical Director) had indicated that when the European Public Assessment Report (EPR) became available, a further submission for funding the additional costs would be made to the NHSE Clinical Panel. This suggested the peer review requirement might no longer be necessary. The EPR was released on 26th June.

SMA UK advised the community they would:

• continue to make every effort to work jointly with the other PAGs (which now also included Treat SMA), clinicians and NHSE to progress access to the EAP.
• continue to support any family trying to access the EAP in the UK by writing on their behalf to the CEOs of NHS Trusts and NHSE. This included any families currently travelling to Europe who would need access in the UK as soon as this option closes.
• try to collect information about all children waiting to access the UK EAP, so that we could discuss the national picture with clinicians and NHS funding bodies. A form to register this information was made available.

At this time our Support Team Manager joined a small confidential NHSE working party to address access including individual family / child needs and requests. This work could not be reported to the community.

15th May: Following our request, Biogen responded to James Palmer’s comments. They advised that they had, at the request of NHSE, provided documentation to support the business case for NHSE supporting the additional aspects of care required to administer treatment:

“This involved the provision of publicly available data outlining the clinical evidence base for nusinersen as well as estimates of additional funding that might be required by the NHS to support children receiving the drug.”

They advised that,

“the request by NHSE to view the clinical data in a peer-reviewed journal is something we are actively pursuing and plans to publish the full results of the Phase III studies are in development. In the interim, Phase III data has been presented at international scientific congresses as is normal prior to full publication. However, it is important to note that the Phase II data has already been published in a peer-reviewed journal, The Lancet.”

“The preparation of data for submission to a peer-reviewed journal requires a number of months for consolidation, analysis and preparation. Biogen’s timelines for this are in line with the standard process for publication of pivotal clinical trial data. Under usual embargo conditions, a manuscript submitted to a medical journal for publication must not be disclosed until the publication date. Biogen is optimistic that publication can be confirmed in the summer.”

NHS England had asked Biogen to fund ancillary costs:

“It is fundamental that in partnership with the NHS, Biogen understands specifically how any additional funding would be applied at each existing and potential EAP site to resolve its infrastructure challenges. Biogen has offered to work with individual hospitals to assess this. Biogen remains committed to continue these discussions and to review what is possible.”

24th April: SMA UK, Muscular Dystrophy UK, GOSH clinicians and Biogen representatives met with the Clinical Director of Specialised Commissioning at NHS England, James Palmer, for urgent talks on the EAP reporting on this to the community on 10th May.

Despite the best efforts of doctors, only a small number of infants were being treated due to limited capacity at specialist hospitals.

James Palmer told the group that though he understood the urgency for families, NHS England was not yet able to confirm any support for the EAP. This was because of a rule which required companies to have their trial results published in a peer review journal before they could qualify for NHS England support. As soon as this happened NHSE would review the possibility again.

Representatives pointed out that this rule was totally at odds with the severely life-limiting nature of SMA Type 1 and the urgency facing babies and their families. This requirement was not even insisted on by major regulators such as the European Medicines Agency and the FDA in the United States (both of whom had now approved Spinraza), nor for decision makers at NICE.

Additionally, NHS England said they had no power to speed up the NICE process in any way. NHS England suggested that Biogen could consider making a decision to include treatment costs as part of their commitment to the EAP.

We asked the community to write to the CEO of NHS England, Simon Stevens, urging fast action on Spinraza.

5th April: 70 people – North Star clinicians, SMA REACH UK and SMA UK send open letter to NICE and NHS England asking NHS England to urgently speed up access to the EAP fund the administration costs of the programme.

7th March: Following SMA UK’s request, Biogen updated the community and advised that discussions were taking place with NHS England and members of the SMA clinical community to ensure that the UK EAP is put on a more sustainable footing in order to minimise piecemeal and ad hoc access, not only then but in the future. They outlined that Trusts had to undertake feasibility checks to determine that all required ancillary resources were available; e.g. appropriately trained personnel, clinic time and space and costs and time associated with supportive care and management. For sites that were up and running, patient numbers had been necessarily limited as a result of infrastructure and service set up resulting in the need for treating physicians to clinically prioritise accordingly.

The concept of having a number of administering centres to operate as ‘hub sites’ to accommodate patients from a larger geographical area, from referring ‘spoke’ sites, was under discussion with clinicians, NHS England and PAGs as well as the criteria to define the highest clinical need and necessary prioritisation.

20th January: The PAGs report from their further meeting with Biogen that other UK Centres had also approached the company. Though Biogen may have agreed and given the ‘green light’ to provide the drug to that Centre, there had to also be local NHS Trust agreement to provide resources to administer the treatment and agree local inclusion criteria.

2018

November 2018 – May 2019: Biogen’s decision left infants in England, Wales and Northern Ireland newly diagnosed with SMA Type 1 with no access to treatment during this time and families in the most devastating position.

1st November: Biogen closed the programme to new infants in England, Northern Ireland and Wales despite NICE still not having made a final decision whether it would recommend nusinersen for funding by the NHS. We strongly urged Biogen not to take this step and, following this, continued to advocate for an extension of the programme or a ‘bridging solution’ until such time as NICE made its final decision.

More than 80 children in the UK remained on the EAP. Biogen advised this was the most for any country in the world and that they had reached the limit of their willingness to, as they put it, ‘continue to support the NHS’ – due largely to their frustrations with the NICE process.

May: Following Scotland’s decision for the NHS to fund access for children with SMA Type 1, the EAP closed there.

Following advocacy by clinicians and patient groups, NHSE announced revised policy that provided new funding to cover all hospital costs for administering nusinersen to all children diagnosed by age 7 months, no matter what their SMN2 copy number. Additionally, children with SMA Type 1 who were diagnosed before 4th August 2017, who were older than this and were not already on the EAP, were also eligible for treatment if their medical team agreed it could potentially be beneficial.

2019

15th May: Following the NICE recommendation for NHS funding of nusinersen, Biogen committed to reopen the EAP for infants newly diagnosed with SMA Type 1 in England, Wales and Northern Ireland until the new guidance was finally published with NHS England then starting to take over funding completely from July 2019.