Zolgensma Treatment in England - FAQs

Page last updated: 7th December 2021

For the latest updates from England’s National Multidisciplinary Team (NMDT) about the roll-out of the programme, including which children are now being referred, please see this page.

Our thanks to:

  • Novartis and NHS England for answering the questions below in April and May 2021.
  • Prof Francesco Muntoni (Consultant Paediatric Neurologist, GOSH), Dr Anne-Marie Childs (Consultant Paediatric Neurologist, Leeds) and Fiona Marley (Head of Highly Specialised Commissioning, NHS England) took part in our webinar on 21st April - we have added some of what they said here as well. 

Q.1. If my child is eligible for treatment, what safety and screening tests will need to be done and when?

A.1. Novartis/NHS England: Once your child has had the genetic test confirming they have 5q SMA with a bi-allelic mutation in the SMN1 gene and that they have:

  • clinical diagnosis of SMA Type 1, or
  • 5q SMA with a bi-allelic mutation in the SMN1 gene and up to 3 copies of the SMN2 gene.

They will need to be assessed at one of the specialist paediatric neuromuscular centres. At the centre, your child will be weighed and will need to have a range of blood tests to make sure it is safe for your child to have gene therapy. These tests include: 

  • AAV9 antibody testing
  • liver function tests
  • full blood count
  • kidney function
  • cardiac enzymes

It should be possible to complete these tests and have the results within a few days. Genetic tests can take a few weeks.

A small number of children may have developed AAV
antibodies before they are tested. Depending on what is called the antibody titre level, the presence of these antibodies could mean that it’s not possible to administer Zolgensma. Recent evidence suggests that only a small number of children may become ineligible for this reason (around 5 in 100 children tested). If AAV9 antibody titres are reported to be above 1:50, your child may be re-tested. AAV9 antibody results are valid for 30 days.

If the results of the other tests (liver function, full blood count, kidney function, cardiac enzymes) are not clear, these may indicate it wouldn’t be safe to administer Zolgensma. Any such results would be discussed fully with you.

Q.2. What advice is there about how to keep children as well and healthy as possible to optimise their chance of accessing Zolgensma treatment?

A.2. Dr Anne-Marie Childs said: ‘The Standards of Care (SoC) that we work to for children and infants with SMA Type 1 are there to try and keep children as well as possible and to support them from some of the challenges that you face when you have SMA Type 1. That is making sure that you’re in a centre where you can have care for your appropriate ventilation support, thinking, if necessary, about effective management of infections, effective secretion clearance. It’s making sure that we have good nutritional support for children, that they’re able to safely get the nutrition they need. That might mean they need some kind of enteral feeding, potentially with a nasogastric tube or possibly with a gastrostomy, and that they’ve got attention to their postural care and management with appropriate physiotherapy, and that families are in a centre where they’ve got access to the expertise that they need and everybody’s working together in the best interests to deliver that SoC. So, it’s very difficult to say what an individual family should do or not do to prevent their child getting infection because children are born into families with other siblings and it’s about individual families working in a system that they feel comfortable with, that allows them the best possible quality of life. I think if we follow the SoC then we’re doing the best we can to keep children as well as possible until they can benefit from these therapies that we’re talking about’.

Prof Francesco Muntoni also added: ‘...time is the essence, and the good news is that there are drugs, even if it wasn’t immediately Zolgensma next week, but there are drugs that are effective that can be accessed rapidly. That I think is the priority, not to be fixated with one or the other or the third or fourth, but to start any of these effective treatments as soon as possible. That allows to get into a rational mode of keeping your child in the best possible health without being concerned that if he or she was on Spinraza, or on Risdiplam, will not be eligible for Zolgensma. That’s a concern you shouldn’t have.'

Q.3. Do we need to isolate for my child to have zolgensma therapy?

A.3. Novartis/NHS England: ‘It’s not necessary to isolate to receive gene therapy or because of treatment with gene therapy:

  • AAV9 antibody results are valid for 30 days.  
  • The AAVvector is not able to replicate so there are no risks to other people.

Isolation would only be necessary due, for example, to Covid 19 and Government guidance that affects you due to your personal circumstances.'

Q.4. How is the actual treatment delivered? How long does it take?

A.4. Novartis: ‘Zolgensma is administered in a specialist hospital as a one-time intravenous (IV) infusion. It takes over 60 minutes to deliver the treatment.'

Q.5. Does the treatment hurt?

A.5. Novartis: ‘There is a need to set up a drip (intravenous cannulation) for your child – which usually goes into the arm. This does involve the sensation of a sharp scratch, the infusion itself should not cause any pain.' 

Please also see the NMDT Updates and Zolgensma - Six Months On video.

Q.6. What if my child is too unwell for treatment on the day, or there is a problem with staffing or treatment delivery at the Centre?

A.6. Novartis: ‘If your child is unwell or there are other issues at the centre it may be necessary to temporarily delay treatment of your child. Your treating physician will make that decision.’ 

Q.7. Immediately after treatment what happens? How long do we need to stay at the Centre? When can we go home?

A.7. Novartis/NHS England: ‘Your child will normally need to be admitted at the infusion centre the day before the infusion to allow sufficient time for pre-infusion tests and to start oral prednisolone (a common steroid treatment) to reduce liver side effects). After receiving the infusion, your child will need to stay in hospital for monitoring. Depending on blood test results and as long as there are no complications, children may be able to go home within a few days but with supervision from the infusion centre. In some cases, children and families may need to stay in accommodation close to the infusion centre. The oral steroids will continue for at least two months.’

Please also see the NMDT Updates and Zolgensma - Six Months On video.

Q.8. What side effects or complications could there be that need to be watched for?

A.8. Novartis/NHS England: ‘Zolgensma has a manageable safety profile when initiated and administered in clinical centres and supervised by a physician experienced in the management of children with SMA.

The most common side effects (which may affect more than 1 in 10 people) are raised liver enzymes and vomiting. It is important that parents have a full discussion about these and other less common side effects with their treating clinician.

Information for parents/carers is available in the Child Information Leaflet at Zolgensma, INN-Zolgensma (medicines.org.uk)

Please also see the Zolgensma - Six Months On video.

Q.9. What care do we need to put in place when we get home?

A.9. Novartis: ‘The active substance in Zolgensma may temporarily be excreted through your child’s bodily waste. Careful hand hygiene and care with the disposal of any nappies for at least one month after infusion is recommended in their Package Information Leaflet.

The International Standards of Care for SMA are the guidelines for care for all children with SMA – whatever drug treatment they are receiving. A copy of the family friendly guide can be found here. Your child may need any usual supportive care advised by their clinical team to continue when they go home. They will also need to attend for regular periodic blood test results and follow up clinic appointments for some time following their infusion. These may be able to be carried out locally to your home. Your clinical team will advise you on this. How long this will need to carry on for will depend on your individual child’s needs and should be discussed with your treating clinician.’

Please also see the Zolgensma - Six Months On video.

Q.10. What help will we be given to get to the treatment Centre and with accommodation and food during all these stages?

A.10. Novartis/NHS England: As Zolgensma will only be available in a small number of highly-specialised infusion centres in the UK, this may mean that travel away from home is required. However, gene therapy is a one-time treatment and so the impact on families should be limited. It is expected that ongoing monitoring and clinic visits should be able to be done more locally to the family home.

In England, the four centres have confirmed what arrangements they will put in place for parents / carers to stay close to their child.

Travel costs will be met in line with standard NHS Healthcare Travel Costs SchemeYou will be responsible for arranging any time off work or childcare arrangements for other children. The cost of food will not usually be reimbursed. If you need help with organising or funding arrangements, please talk to the referring or treatment centre and / or the One Gene Therapy Family Liaison Nurse.

Q.11. What support is provided throughout and following treatment, including emotional and psychological?

A.11. All the gene therapy centres have facilities in place to support families holistically throughout the treatment period. 

Q.12. If my child is on another treatment at the moment and eligible to move to Zolgensma, what do I need to know?

A.12. Novartis/NHS England: ‘There are no clinical trials that have looked at treatment outcomes when Zolgensma has been given after other active treatment therapies. There is a growing body of real-world evidence where it has been used; treatment has been successful, and children have continued to attain milestones.

The NMDT will advise on how long the period should be between an eligible patient having treatment with nusinersen or risdiplam and having treatment with Zolgensma.

SMA UK: Please see NMDT Updates for information about which children who are already receiving another treatment are now being referred to the NMDT and the Zolgensma - Six Months On video.

Any supportive treatment that your child may be receiving to help control their SMA symptoms is likely to continue. If your child is currently receiving another active drug treatment for SMA, they will need to come off this to allow them to have Zolgensma. 

Q.13. Can my child resume the treatment they have stopped after they have had Zolgensma?

A.13. Novartis/NHS England: has told us: ‘Given that Zolgensma is designed to address the genetic root cause of SMA it is not anticipated there should be a need to receive other currently available active drug treatments.' For more information about how Zolgensma works, please go here.

SMA UK: NHSE&I have now issued their advice - see MAA Appendix A - that this is only possible if Zolgensma treatment is not successful. 

Q.14. Can my child have a further treatment later on – after having had Zolgensma?

A.14. Novartis/NHS England: 'Zolgensma is designed to address the genetic root cause of SMA and continue working into the long-term following a single dose. An immune response to the adeno-associated viral vector that delivers the therapeutic gene will occur after infusion of onasemnogene abeparvovec. Repeat Zolgensma therapy would provoke an immune response and therefore a repeat round of therapy cannot be given.' For more information about how Zolgensma works, please go here.

'As Zolgensma is designed to address the genetic root cause of SMA it’s not anticipated there should be a need to receive other currently available drug treatments after gene therapy. Clinicians will need to discuss any exceptional cases with NHS England or equivalent organisations in Scotland, Wales and Northern Ireland.'

19th November 2021: NHSE&I have now issued their advice - see MAA Appendix A - that this is only possible if Zolgensma treatment is not successful. 

Q.15. What information will be collected about my child’s treatment and outcomes?

A.15. Novartis/NHS England: ‘Any requirements for the collection of child information will be described in the NICE Final Guidance and will be developed in conjunction with the gene therapy centres, SMA REACH and the wider expert clinical community. Novartis Gene Therapies would hope that the clinical data of children treated with Zolgensma will be entered into the national SMA registry (SMA Reach) so that doctors can gain the best understanding of how the therapy is being used and how children are benefitting.

Data on your child’s developmental milestones, any need for support with feeding and breathing, quality of life measures and need for additional treatments will be part of the data collection. This data will be collected as part of the routine follow up of your child and will link into existing data collection processes with SMA REACH. The gene therapy centres will also use this data for audit and monitoring purposes.'

Q.16. Do children have to live in the UK to access this treatment?

A.16. NHS England: Hospital treatment is free of charge for people who are ordinarily resident in the UK. This does not depend on nationality, payment of UK taxes, National Insurance contributions, being registered with a GP, having an NHS number, or owning property in the UK. The legal duty to assess patients’ eligibility for hospital treatment lies with the NHS body providing treatment. Most hospitals have overseas visitors’ managers or their equivalents to do this assessment. They make their assessments in line with the charging regulations and based on evidence provided by the patient.

EU residents are able to access treatment in the UK with the explicit agreement of their home country. It is likely that prioritisation will be given in the first instance to treating all eligible UK patients. There is a mechanism for centres to be reimbursed for treatment for patients coming from the EU.

Q.17. What is a safe weight or maximum age for treatment with zolgensma?

A.17. In our 21st April webinar, questions were asked about this:

Dr Anne-Marie Childs said: ‘I think it’s really important we do our best to keep every individual infant and child as healthy as possible. Children need to have a weight that allows them to maintain their capacity to deal with infection, to grow and develop normally. So, one of the things I would be really concerned about would be is if we left families thinking they had to restrict the weight of their child to fulfil the criteria. Making decisions about who’s going to benefit from treatment, it’s not going to be about a single parameter – it’s not going to just revolve around your age or your weight – but it is going to be important that the child is able to tolerate the treatment and is as well as possible. I would encourage families to follow sensible advice and guidance and continue to work with their treatment centres to keep their child as well as possible.’ 

Prof Francesco Muntoni pointed out: ‘The treatment has been mostly at the moment trialled in children with SMA Type 1, with the exception that some of the pre-symptomatic children were eligible even if expected to develop Type 2 SMA and as you are aware it’s the copy number of SMN that determines the probability to develop Type 1 or more severe Type 2 SMA. There has not been treatment in others or older individuals, there was a clinical trial for individuals with Type 2 SMA who were older, but because there is an issue of the amount of virus that you can safely give to larger and bigger individuals, this particular clinical trial was done by giving the drug directly in the spinal fluid, but at the moment the clinical trial is on hold and the reason why this is on hold is because there is a theoretical possibility from animal models of some toxicity that has not been observed in the human but following maximum safety guidelines, that study has been re-evaluated in terms of the risk benefit. So, the point I’m making is that the experience really is internationally only with Type 1 children with the exception of the pre-symptomatic who may have otherwise been expected to develop Type 2 SMA so that already gives you a sense that that’s why the treatment at the moment won’t be available for adults or people with milder forms of SMA because they have never been studied using this particular route of administration.’

Dr Anne-Marie Childs added: ‘...like all treatments there’s an important responsibility to consider the risks and benefits of treatment and we’re still learning about that, I think. I think for all of the treatments that we now have available for SMA we understand that if they’re given as early as possible in the disease process before any irreversible damage has occurred to the nerves then that’s likely to yield the greatest benefits, and I think one of the challenges for Zolgensma is this increased risk as the children become heavier and need an increasingly large viral load to deliver an effective treatment and so that does mean the risks of this treatment are really important to consider because we know from experience of other clinical trials of gene therapy that there have been some really severe side effects and outcomes when we give that degree of viral load to a young child.'

Novartis has started a global clinical trial of Zolgensma with 24 patients weighing between 8 and 21 kgs. Details are here.

Q.18. What about treatment for children who have SMA Type 3?

A.18. In our webinar on 21st April:

Prof Francesco Muntoni commented: ‘There are several problems if a child with Type 3 was going to receive this: firstly, it’s outside, nobody has received that particular drug intravenously at that age and so on; secondly I think there are some concerns that the amount that you need to give intravenously to reach the brain may cause substantial adverse events, and also we don’t know how effective it would be given in the veins. So, the reality that this particular drug, and in this particular mode of administration, it would not really be possible to give it to individuals with Type 3 SMA. There is ongoing work the company is doing to try to assess how safe it would be to give a drug like this one to people, including people with Type 3 SMA, but if given directly via the spinal fluid.’

Q.19. Does the UK offer private access now?

A.19. Novartis/NHS England: ‘We are not aware of any treatment with Zolgensma that has taken place privately in England. It would be for the individual infusion centres to decide whether or not to offer private treatment and to decide on the eligibility criteria for these patients. The price charged for private patients or any other patient not eligible for treatment under the NHS is not subject to the agreement in place between Novartis and NHS England and would be subject to a separate commercial pricing agreement.

Zolgensma should be initiated and administered in clinical centres and supervised by a physician experienced in the management of children with SMA.'

In our webinar on 21st April:

Fiona Marley said: ‘So, I guess it will be down to the four centres to decide whether or not they want to offer a private service and I guess also clearly we’re very keen that all eligible patients on the NHS are the ones who are prioritised for treatment. And also, to say as you may have seen in the announcement from NHS England, we have been able to negotiate a special price with the company that’s just for NHS patients – so it would be for the company to decide what they charge for people who are accessing the treatment privately.’

Prof Francesco Muntoni commented: ‘I think an important concept is that while the treatment is a simple treatment to give because it is an intravenous injection, the infrastructure to be able to do this properly requires some thinking so is not something that could be given by any provider that can just access the vein of the child. Therefore, I think it’s important to consider the capacity to be able to deliver this in a multidisciplinary setting and doing it properly. So, I think that at this point in time, to make sure that things happen properly is probably more important than thinking, “what about patients outside the NHS?”.'