1.1 Onasemnogene abeparvovec is recommended as an option for treating 5q spinal muscular atrophy (SMA) with a bi-allelic mutation in the SMN1 gene and a clinical diagnosis of type 1 SMA in babies, only if:
they are aged 7 to 12 months, and their treatment is agreed by the national multidisciplinary team.
It is only recommended for these groups if:
permanent ventilation for more than 16 hours per day or a tracheostomy is not needed
the company provides it according to the commercial arrangement.
1.2 For babies aged 7 to 12 months, the national multidisciplinary team should develop auditable criteria to enable onasemnogene abeparvovec to be allocated to babies in whom treatment will give them at least a 70% chance of being able to sit independently.
1.3 Onasemnogene abeparvovec is recommended as an option for treating presymptomatic 5q SMA with a bi-allelic mutation in the SMN1 gene and up to 3 copies of the SMN2 gene in babies. It is recommended only if the conditions in the managed access agreement are followed.
Why the committee made these recommendations
SMA is a rare genetic condition. The most severe types affect babies and young children, and are fatal when treated with best supportive care. Survival is expected to be around 2 years. A few children can be diagnosed with SMA before symptoms appear if a sibling has been diagnosed with SMA. Presymptomatic diagnosis is done through genetic testing. Currently, children with presymptomatic or types 1, 2 or 3 SMA can have treatment with nusinersen within a managed access agreement. If nusinersen is not a treatment option, then children have best supportive care. Because nusinersen is not routinely commissioned for use in the NHS, it could not be considered as a comparator in this evaluation.
For babies with type 1 SMA who are 6 months or younger at the start of treatment, and who do not need permanent ventilation for more than 16 hours per day or a tracheostomy, evidence from clinical studies suggests that onasemnogene abeparvovec is effective. But the studies are small and do not compare onasemnogene abeparvovec with other treatments, so it is difficult to establish how well it works. Also, there is very limited evidence for babies with type 1 SMA who are older than 6 months at the start of treatment. However, clinical experts advise that some babies aged between 7 and 12 months would be expected to have similar benefit to those 6 months and younger. There is also a lack of long-term evidence, and no evidence in more progressed type 1 SMA.
Because of the uncertainty in the clinical data, the cost-effectiveness estimates for onasemnogene abeparvovec for treating type 1 SMA are uncertain. However, they are likely to be within the range that NICE considers an effective use of NHS resources for highly specialised technologies for:
babies 6 months and younger
babies aged 7 to 12 months if it is likely that they will have a similar benefit from treatment with onasemnogene abeparvovec as younger babies.
So, onasemnogene abeparvovec is recommended for use in the NHS for both these groups. Because of the limited trial data for babies aged 7 to 12 months, their treatment should be discussed by a national multidisciplinary team.
There is no evidence available for treatment with onasemnogene abeparvovec in babies with type 2 or 3 SMA with up to 3 copies of the SMN2 gene. Nor is there any evidence for its use in babies with type 1 SMA treated with nusinersen. Also, there are no ongoing clinical trials in these populations. Therefore, no recommendation can be made based on the clinical and cost effectiveness of onasemnogene abeparvovec treatment for these populations.
The evidence in babies with SMA with up to 3 copies of the SMN2 gene who have not yet developed symptoms is uncertain because it comes from a study that is still collecting data. However, some of the uncertainty will be resolved when more data have been collected. Also, the clinical experts expect the treatment to be effective in babies who do not have symptoms yet. The cost-effectiveness estimates are also uncertain. But onasemnogene abeparvovec could provide value for money within the context of a highly specialised service for this group. Therefore, it is recommended through a managed access agreement while further data are collected.