Spinal muscular atrophy (SMA) is a devastating condition which, in the most severe cases, leaves babies with a life expectancy of rarely more than two years. Spinraza (also known as nusinersen) has been developed by pharmaceutical company Biogen and is the first and only treatment for people with SMA. It was approved by the European Medicines Agency (EMA) in June 2017. Clinical trials showed the treatment led to a significant improvement in children’s motor function, allowing them to achieve, or maintain, physical milestones that they would never reach without treatment, and to survive longer than expected considering the typical course of the condition. Some children who would never have sat independently have been able to and some have also been able to crawl and even walk.
For more information, please contact Clare Lucas on firstname.lastname@example.org or call 020 7803 4838.
Questions and answers
Spinal muscular atrophy (SMA) is a rare inherited neuromuscular condition where the loss of motor neurons cause muscles to waste away, resulting in progressive muscular weakness and loss of movement. It can affect crawling and walking ability, arm, hand, head and neck movement, breathing and swallowing.
There are four types of SMA:
- SMA Type 1: Symptoms appear within the first few months of life, sometimes before birth. Children are never able to sit unaided and rarely survive their second birthday without treatment.
- SMA Type 2: Symptoms usually appear between 7-18 months of age. Children are never able to stand unaided. Although the condition may shorten life expectancy, improvements in care standards mean that the majority of people can live long and fulfilling lives.
- SMA Type 3: Symptoms appear after 18 months of age. Children are able to stand and walk, but will become less able to walk over time. Life expectancy is normal and most people can live long independent lives.
- SMA Type 4 (also known as adult onset SMA): Symptoms appear in adulthood. It is not a life-threatening condition.
There are estimated to be up to 1,300 children and adults living with SMA in the UK. In 2015, approximately 78 babies were born with SMA and, of these, 43 had SMA Type 1 – the most aggressive type of SMA.
Spinraza is the first and only treatment for SMA. Developed by pharmaceutical company Biogen, clinical trials have shown significant improvement in children’s motor function; for the first time, we have seen children with SMA Type 1 crawl and even walk. Families of children who have received the drug often report noticeable improvements from the start of treatment. The drug proved so effective in clinical trials with children with SMA Type 1 that in August 2016 they were stopped early so all the children could access the drug.
The drug also has promise for the other types of SMA; motor function for children with SMA Type 2 and 3 was significantly improved in trials. In April 2019, a three-year study of 28 children aged between two and 15, which was published in the scientific journal Neurology, highlighted meaningful improvements that extended over time. Some of these improvements were remarkably different to the natural progression of the condition when left untreated. In particular, a two-year-old child with SMA Type 2 gained the ability to walk independently after receiving Spinraza, while two children with SMA Type 3 who had lost the ability to walk before taking the drug regained it during the study.
While the drug was highly effective in most treated children, there were some who did not respond to the treatment. Some patients may also be too weak to receive the intrathecal injection via a lumbar puncture.
England, Wales and Northern Ireland: Biogen set up an Expanded Access Programme (EAP) in 2016 following successful clinical trials. This provides the drug for free while assessments into its provision are made. However, on 22 August 2018 it was announced that the scheme would close to new entrants in November 2018.
Now that NICE, Biogen and NHS England have come to an arrangement on a Managed Access Agreement, children and adults with SMA Types 1, 2 and 3 are set to access the treatment in England, providing they were diagnosed before the age of 18. Muscular Dystrophy UK will be pushing for this to be implemented as quickly as possible.
Scotland: The Scottish Medicines Consortium (SMC), the Scottish equivalent of NICE, approved Spinraza for use on the NHS for children with SMA Type 1 in May, replacing the EAP.
In February, it was announced that – subject to sign-off – the treatment would be made available for people with SMA Type 2 and Type 3 through a new ultra-orphan pathway introduced by the government. While this is still awaiting final sign-off, patients are considered on a case-by-case basis and some have received treatment already.
Spinraza was appraised by NICE through its Single Technology Appraisal (STA) process, which is traditionally used for treatments for more common conditions. This process started in January 2018, meaning patients have faced a lengthy 16-month wait up until this point.
NICE gave the drug a negative opinion in an appraisal consultation document published on 14 August 2018. It had been due to make a final recommendation in November 2018.
Part of the delay has been because of the unsuitability of NICE’s appraisal routes. There are only two: the STA route, through which Spinraza would typically be too expensive; and a specialist treatment route, unsuitable for Spinraza as it can benefit too many people. This is not the first time that a treatment to help people with muscle-wasting conditions has been heavily delayed. We need to see an overhaul of these routes to ensure rare disease drugs aren’t held up in future.
Having reached an agreement with Biogen and NHS England, NICE is set to recommend the treatment for children and adults with SMA Type 1, 2 and 3, providing they were diagnosed before the age of 18. This will be provided through a temporary scheme, known as a managed access agreement (MAA).
See the timeline at the end of this page for further details.
A managed access agreement (MAA) is an interim scheme that will allow patients with SMA to access Spinraza, so that data can be gathered on the treatment’s effectiveness while ensuring access. The aim of an MAA is to temporarily deliver a treatment through the NHS while a longer-term agreement to provide it is agreed. The length of time a MAA is implemented can vary, but three to five years is typical.
NICE is now expected to formally recommend Spinraza and Wales and Northern Ireland usually follow NICE guidance. Muscular Dystrophy UK will be seeking assurances that they will be doing so in this case. This will mean that the treatment can be accessed UK-wide.
Muscular Dystrophy UK has worked closely with other SMA charities in fighting for access and is delighted for families and patients. This would not have been possible without the support and hard work of clinicians, SMA charities, MPs, and, above all, families and people with the condition. Thanks to their tireless campaigning, families should face a brighter future.
We’re delighted that people with SMA Types 1, 2 and 3 will be able to access Spinraza. We have heard from families already receiving the treatment that children are reaching milestones never thought possible and are living longer. But it never should have taken this long to reach a decision.
We need to ensure this is implemented as soon as possible, and made available UK-wide. We will also be pushing for guidance and support to be made available to patients and families about the administration of the drug.
The lengthy, frustrating delays which we have seen throughout this process must not be allowed to happen again. Muscular Dystrophy UK will continue to call for changes to the appraisal system for new treatments for rare diseases to make it fit for purpose for future treatments for rare conditions.
MDUK will liaise with Biogen and NHS England to ensure that information and support for patients about the treatment process and side effects is put in place.
Before individual European countries examine a treatment, they are first of all licensed by the European Medicines Agency (EMA). Spinraza was recommended in April 2017 by the EMA to be licensed as a treatment for SMA Types 1, 2, 3, 4. In June 2017, the European Commission finalised the recommendation.
Spinraza is available for children and some adults with all types of SMA in 24 European countries. Negotiations are under way in other countries. More widely, Spinraza was approved in the United States in December 2016, and has gained additional approvals in Korea, Canada, Japan, Brazil and Australia since then.
Patients with SMA lack a protein called ‘survival motor neuron’ (SMN) protein, which is essential for motor neurons to survive and function normally. The SMN protein is made from two genes, SMN1 and SMN2. Patients with SMA lack the SMN1 gene but have the SMN2 gene, which mostly produces a short SMN protein that does not work as well as a full-length protein.
Spinraza is a synthetic anti-sense oligonucleotide (a type of genetic material) that enables the SMN2 gene to produce full length protein, which is able to work normally. This replaces the missing protein, thereby relieving the symptoms of the disease.
Spinraza is administered through an injection into the spinal canal in an established procedure known as an intrathecal injection. This delivers medication through the lower back via a lumbar puncture and directly into the central nervous system. This procedure is performed under the direction of healthcare providers experienced in administering lumbar punctures and requires special precautions – either sedation or general anaesthetic.
The list price of Spinraza is £75,000 per vial (excluding VAT; British National Formulary, accessed June 2018). This would mean the total annual treatment cost is £450,000 for the first year and £225,000 for subsequent years.
Biogen only presented evidence for SMA Types 1, 2 and 3, and the consensus is that Spinraza has greatest impact on people with those types. NICE can provide more information on its website.
You may come across different acronyms when hearing people talk about Spinraza. Below is a guide to what these mean.
AAP: Accelerated Access Programme. A government scheme to fast-track breakthrough treatments announced in November 2017. We are waiting to hear if rare disease drugs will be eligible for it.
EAP: Expanded Access Programme. A special scheme currently providing access to Spinraza for those with SMA Type 1 from the pharmaceutical company Biogen. This was closed on 1 November 2018.
EMA: European Medicines Agency. Pharmaceutical treatments typically need to get a licence for marketing a drug from the EMA before they are assessed by NICE. The EMA approved Spinraza in 2017.
HST: Highly Specialised Technology route. One of the two routes, along with STA, through which NICE assess treatments in England.
MAA: Managed Access Agreement. This is an agreement to provide treatment on the NHS while more data is gathered on its efficacy, and we want to see one put in place for Spinraza in England, Wales and Northern Ireland.
NICE: National Institute for Health and Care Excellence. NICE is in charge of recommending whether treatments should be funded on the NHS.
PACE: Patient and Clinical Experts. A special meeting held by the SMC to garner views.
SMA: Spinal muscular atrophy.
SMC: Scottish Medicines Consortium. The SMC is in charge of recommending treatments for provision on the NHS in Scotland.
STA: Single Technology Appraisal route. The main route through which NICE assesses treatments in England, including Spinraza.
August 2016: The drug proves so effective in clinical trials with children with SMA Type 1 that they are stopped early so that all the children can access the drug. Biogen then opens its Expanded Access Programme (EAP) for Spinraza, offering the drug free to all children with SMA Type 1 who showed signs of SMA before six months of age in the UK.
21 April 2017: The drug is recommended by the European Medicines Agency (EMA) to be licensed as a treatment for SMA Types 1, 2, 3, 4.
1 June 2017: The European Commission finalises the recommendation by the European Medicines Agency (EMA).
August 2017: NHS England agrees to support delivery costs for Spinraza, but only for children with two copies of the SMN2 gene (around 80% of children), as these were the only children involved in the clinical trials.
November 2017: The Department of Health announces a new, fast-track route into the NHS for ‘breakthrough’ medicines and technologies, known as the Accelerated Access Pathway (AAP). Five drugs a year will benefit – but no criteria is given and the scope of the scheme is unclear.
November 2017: The Scottish Medicines Consortium (SMC) starts its appraisal of Spinraza.
January 2018: NICE announces it will begin its appraisal of Spinraza for SMA Types 1, 2, 3 and 4 through its Single Technology Appraisal (STA) route. Discussions of an interim scheme, known as a managed access agreement (MAA), also get under way between manufacturers Biogen, NHS England, and NICE.
13 March 2018: Families and charities make submissions and give evidence on the benefits of Spinraza at a Patient and Clinical Experts (PACE) meeting held by the Scottish Medicines Consortium (SMC).
3 April 2018: The Scottish Medicines Consortium (SMC) holds a second meeting for final submissions from charities and families on why Spinraza should be approved in Scotland.
7 May 2018: The Scottish Medicines Consortium (SMC)’s appraisal of Spinraza is published. It recommends it for use on the NHS in Scotland for children with Type 1 SMA – but not Types 2 and 3.
14 August 2018: NICE publishes its appraisal consultation document for Spinraza, setting out provisional recommendations for not approving the treatment for use on the NHS in England. This was originally expected to be released in June.
22 August 2018: Biogen announces it will be stopping the Expanded Access Programme from 1 November for all babies who are diagnosed after this date. Biogen says babies and children currently on this scheme will not be affected.
8 October 2018: The Scottish Government launches the ultra-orphan pathway for rare treatments.
1 November 2018: Biogen’s Expanded Access Programme is closed to new patients.
13 February 2019: Announcement is made that Spinraza is due to be made available on the NHS in Scotland for children and adults with SMA Types 1, 2 and 3, having been assessed through an ultra-orphan pathway.
6 March 2019: NICE holds a third committee meeting to discuss Spinraza.
8 May 2019: A fourth NICE committee meeting, held in private, is held to discuss Spinraza.
15 May 2019: NICE and NHS England announce they have negotiated a deal with Biogen to make Spinraza available in the NHS for children and adults with SMA Types 1, 2 and 3, through a managed access agreement. This paves the way for NICE to formally recommend the treatment.