UK Access Summary:
From Autumn 2016 - February 2019

1. What is it?

Nusinersen, which is marketed as SpinrazaTM, is the first (and currently, the only) potentially available disease-modifying treatment for 5q SMA, which includes SMA Type 1, 2, 3 and 4. 

In early clinical trials, significant numbers of individuals treated with nusinersen showed improvement, including:

  • achieving physical milestones that they would not have reached without treatment
  • maintaining physical milestones that they would not have maintained without treatment
  • surviving longer than expected considering the typical course of their condition

Nusinersen is delivered directly into the Cerebro Spinal Fluid (CSF) using a lumbar puncture (sometimes called intrathecal injections).

Injections are given as follows:

  • On the first day of treatment, day 0
  • Then around day 14, day 28 and day 63
  • Then once every 4 months

2. The global Expanded Access Programme

Autumn 2016, the ENDEAR clinical trial results for children with SMA Type 1 were sufficiently positive for Biogen to end the trial early and for all children in the trial to be transferred to the treatment. Biogen opened their global Expanded Access Programme (EAP) for children with SMA Type 1 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

By January 2017 the EAP had opened in many countries but was only beginning in the UK (at GOSH) as the NHS Trusts didn’t have the funds / capacity to cover the administration costs of delivering the treatment. Families had started to travel to Europe to access the treatment via the EAP at considerable cost to themselves and with all the stress and risks of travelling with a very sick child.

There was a huge amount of advocacy work from clinicians and patient groups with support from MPs (All Party Parliamentary Group 18th July) to open the EAP in the UK. It soon opened in Northern Ireland and Scotland but took until late July 2017 for NHS England to agree to fund the treatment and for the EAP to roll out to other Centres.

This programme closed to new infants on 1st November 2018. More than 80 children remain on the programme. Biogen advised this is the most for any country in the world and has reached the limit of their willingness to continue to support the NHS – due largely to their frustrations with the NICE process (see below).

3. NICE’s appraisal of the treatment for all with 5q SMA

NICE (The National Institute for Health and Care Excellence) is the regulatory body for England which reviews evidence from clinical trials, and the costs of providing the treatment. They then make evidence -based recommendations / issue guidelines. If NICE recommends the drug for use through the NHS, then NHS England is normally expected to fund the treatment within 90 days. 

Key issues with NICE’s approval of nusinersen have been:

  • the length of time this has taken (It’s our understanding that NICE is asked to publish guidance within six months of a product receiving its licence from the EMA though we are also aware that the full NICE approval process for the appraisal route NICE selected (including possible appeals) takes an absolute minimum of 43 weeks, and this process can be much longer. However, whatever is correct, the current 77 weeks since EMA’s licence (as at 25/11) is, we feel, unacceptable)
  • the appraisal process / route NICE set (see below)
  • that NICE’s system is not fit for purpose (see below)

23rd December 2016

The US Food and Drug Administration (FDA) approved nusinersen’s use for both children and adults with SMA Types 1, 2 or 3 SMA.

January 2017

Anticipating that the treatment could be licensed for use in Europe (which is the point at which the Secretary of State / NICE can start to consider a treatment for provision by the NHS), NICE undertook what is called a scoping exercise to gather information about the condition and the treatment and, whether if there were to be an appraisal, this should be as a:

  • Single Technology Appraisal (STA) used for common diseases or
  • Highly Specialised Treatment (HST) used for rare conditions – but with strict criteria limiting this possibility.

An STA has a much lower price threshold for approving a treatment than an HST. It was known that nusinersen has a high price, which Biogen argues is in line with similar products and reflects the research costs etc. and that it would be unlikely to meet the STA cost/benefit (ICER) price requirements

1st June 2017, the European Commission released its report (prepared by the European Medicine Agency (EMA)) approving nusinersen for marketing as a treatment for all with 5q SMA.

Biogen, clinicians and patient advocacy groups waited and waited for NICE to announce that it would be starting its appraisal. We had anticipated hearing this by September 2017 but heard nothing until:

18th January 2018 NICE announced the appraisal would be an STA. Clinicians, patient groups and Biogen made submissions and the first NICE committee meeting to look at all the evidence was in June 2018.

14th August 2018 NICE announced the devastating news that they had not recommended nusinersen for funding by the NHS. This was on the grounds that:

  • Its clinical effectiveness is not yet proven – the treatment hasn’t been trialled for long enough – we argue this is the same for many innovative treatments. NICE indicated that this though would not be a block to possible access via what is called a Managed Access Agreement (MAA). This would be a 3 – 5-year scheme agreed between Biogen, NICE and NHS
  • England (NHSE) that would enable access to treatment and the opportunity to collect further evidence of its clinical benefits and impact on quality of life. 
  • The price is too high. Biogen argues that the package/price they are offering NHS England is the best offer any country in Europe has had and that countries with a lower GDPR than the UK and Scotland (see below) have managed to afford it. Also, the budget /price threshold that Biogen is expected to meet is the one set by the STA process which is much lower than if had been assessed via an HST process (as we and Biogen believe should have been used) so, unless NICE and NHSE budge on this, price is going to continue to block access. Clinicians and patient groups are urging all sides to be flexible in their negotiations.

October 23rd, 2018 NICE held a second committee meeting to review all the responses to its consultation which followed the August decision. Patient and clinical ‘experts’ attended that meeting. A final decision was due by the originally announced date of 21st November 2018 but this date was taken down from NICE’s website.

March 6th 2019 is the date now set for NICE’s third committee meeting.

The key point we have been arguing all along is that the STA route for nusinersen was never going to work and is not fit for a condition like SMA or a treatment like nusinersen. We suggest NICE knows this and that this is why they took so long deciding which route it should follow. Nusinersen/SMA didn’t fit all the very strict HST criteria and there is nothing in between that route and the STA route. This aspect of the NICE appraisal system is not, we suggest fit for purpose. This is being argued at many levels by clinicians, pharmaceutical companies and charities* but is always refuted by the Ministry of Health, NHS England and NICE officials in their public response to letters about it.

4. Scotland

In the meantime, Scotland’s Scottish Medicines Consortium undertook its assessment quickly and efficiently.

On 7th May 2018, Scotland agreed to fund the treatment for those with SMA Type 1. 

On 8th October 2018 the Scottish Government announced their new pathway for ultra-orphan treatments which gave some hope for those with SMA Type 2 or 3. To be eligible for this pathway, a company needs to establish that:

  • The condition has a prevalence of 1 in 50,000 or less in Scotland
  • The medicine has an EMA orphan designation for the condition and this is maintained at time of marketing authorisation
  • The condition is chronic and severely disabling, and
  • The condition requires highly specialised management.

If then the Scottish Medicines Consortium (SMC) consider a treatment clinically effective, it will be made available on the NHS in Scotland for at least three years while further information on its effectiveness is gathered. Following this period, the SMC would then review the evidence and make a final decision on its availability on the NHS in Scotland. 

As of 13th February 2019, subject to successful sign off, nusinersen is expected to be routinely available in Scotland for those with SMA Types 1, 2 and 3 from April 2019.

Read more on this page.

5. Europe and the rest of the world

Canada, we understand, is the only other country with legislation and complex appraisal criteria similar to England. In early October 2018, they approved the use of nusinersen for all types of SMA, as they were able to identify an appraisal tool fit for purposes of SMA. This now left England as the only country in the West (and many of the East) in which nusinersen has not been given an appraisal route that is fit for purposes. You can see Biogen’s updates here.    

6. Finally

In contrast to what has happened to SMA / nusinersen there was quite a bitter irony when CAR-T therapy Kymriah got the “fast-track” recommendation from NICE/NHS England through the Cancer Drugs Fund on 5th September. It took 10 days and was announced on the day we submitted our consultation response to the first committee stage for nusinersen – 462 days after EMA’s marketing approval.

Additionally during this time the original scientists who worked on nusinersen won the 2019 Breakthrough prize (the “Oscars for science”). Biogen was also awarded the international Prix Galien award for Best Biotechnology Product for SPINRAZA (nusinersen), making this its seventh Prix Galien award (country recognitions in the U.S., Germany, Italy, Belgium-Luxembourg, the Netherlands and, ironically, the U.K).

We are very concerned that the NICE system and NHS funding levels are leading us to a place where England is unable to benefit from the very exciting innovations and breakthroughs in drug treatment that are happening all the time. Clinicians are hugely frustrated that they cannot offer their patients treatments they know are working in the rest of the world. We have heard several talk about leaving the NHS and England because of this. More treatments are on their way – families cannot go through the distress of the long wait they have had for this first treatment again. The system must change – click here to read more about this.


November 2018