1. SMA and Nusinersen (Spinraza) The Story So Far....
Jennifer Dunne
Neuromuscular Clinical Nurse Specialist – RHC - Glasgow

2. Aims: Basic genetics of SMA The history of Nusinersen and how it works
Clinical trials
The development and delivery of Nusinersen in RHC – Glasgow
Practical considerations as time goes on
Case study – 1 year on from Nusinersen

3. What is SMA?
SMA is a fault in the gene (SMN1) that codes for the Survival Motor Neurone (SMN)
We have two copies of SMN1, one from each parent.
The affected child is unable to make enough SMN protein as SMN1 is deleted or mutated
Leading to loss of functional motor skills.

4. SMA SMA is unique : second copy of the SMN gene, SMN2
Patients survive owing to the SMN2 gene.
The more SMN2 copies the more SMN protein produced
SMA Type
Onset
Features
Likely SMN2 copy number
Prenatal
Contractures, facial diplegia, respiratory failure 1
< 6 months
Poor tone, weakness, mild contractures, tongue fasciculations 2
6 - 18months
Low tone, absent reflexes, may sit independently
3-4 3
Childhood, > 18 months
Able to walk 25 metres, onset of falls ~ age 2-3 4
Adult onset
Weakness with onset in adulthood
4-8

5. Nusinersen and the SMN2 Gene
Nusinersen is an Antisense Oligonucleotide
small snippets of synthetic genetic material that bind to ribonucleic acid (RNA)

6. Basically Nusinersen
Improves expression of the SMN2 gene, converting it into SMN1 gene, thus increasing the level of SMN protein.

7. History of Nusinersen 2012 development began
2015 Biogen acquired exclusive license
2016 Nusinersen met its primary end point
2016 Biogen opened the Expanded Access Program – due to stop on Nov 2018
2018 (May) SMC approval of Nusinersen on the NHS for SMA 1 only – in Scotland
2018 (Aug) NICE did not approve it as a treatment for SMA – in England

8. Clinical Trails
ENDEAR Phase 3 – 2014 terminated early 2016 CHERISH Phase 3 – 2014 until 2017 (closed early) EMBRACE Phase 2 – 2015 until April 2019 NURTURE Phase 2 – 2015 until Jan 2022 SHINE Phase 3 – 2015 until 2022

9. Delivery of Nusinersen in RHC – Glasgow
2016 Biogen opened ‘Expanded Access Program’
2 patients 1st injection 8th Jun ‘17
3rd patient 1st injection 7th Dec ‘17
4th patient (SMA2) 1st injection 3rd Mar ‘18 - via NHS funding
SMC approval May 2018 – now all funded by NHS

10. Schedule of Treatment
Year 1
Year 2+

11. Practical Considerations
LP procedure is becoming more difficult
Development of scoliosis
The site is developing scar tissue
The patients are getting older and more aware of what we are doing
They are getting stronger - wriggling

12. Practical Considerations
We need to consider aesthetic procedure – midazolam unsuccessful
Need a specific theatre list not just emergency list
Protocol/Guidelines need developed
Implications for adult patients are huge

13. SMA type 1 treated with Nusinersen are not SMA type 2 patients
New Phenotype

14. Case Study – Sophia Diagnosed April 2017 aged 6 months 1 copy of SMN2
1st treatment on 8 June 2017 aged 8 months
Baseline CHOP was 37
After 6th injection 48 but more like 54
No respiratory issues
No feeding issues
Developing scoliosis – referred for lycra suit
Leg length discrepancy

15. At Diagnosis Aged 6 Months

16. Aged 1yr 6 mths – 6 Injections
Sophia
Aged 1yr 6 mths – 6 Injections

17. After 7th Injection – Year 2

18. Thank You Any Questions?