When can Risdiplam or Nusinersen be prescribed after treatment with onasemnogene abeparvovec (Zolgensma)?
When can Risdiplam or Nusinersen be prescribed after treatment with onasemnogene abeparvovec (Zolgensma)?
Page last checked 17th December 2024
These answers are from the 26th January 2022 NICE website >
Further advice was communicated to clinicians in April 2023. This has been added below.
N.B. We use the trade name Zolgensma for ease of reading rather than onasemnogene abeparvovec.
Q.1 What are the clinical circumstances under which it would be appropriate for an individual to continue to have treatment with risdiplam (or nusinersen) after treatment with Zolgensma or to be initiated on treatment with risdiplam (or nusinersen) after treatment with Zolgensma?
A.1. All individuals being considered for treatment with risdiplam (or nusinersen) must meet the Starting criteria and must not meet the Stopping criteria set out in the treatment’s managed access agreement. These criteria include that the individual must not have had successful treatment with Zolgensma.
- Starting criteria for risdiplam
- Stopping criteria for risdiplam
- Starting criteria for nusinersen
- Stopping criteria for nusinersen
The definition of non-successful treatment with Zolgensma is as follows:
(a) A reduction in motor ability, defined as:
Total worsening in scale score corroborated by two consecutive measurements from any two of the following three scales:
- more than 2 points on horizontal kick or 1 point on other HINE scores excluding voluntary grasp
- more than 4 points on the CHOP INTEND scale
- more than 3 points on the RHS scale
A scaled equivalent of these losses would apply if a domain was unmeasurable or not suitable. These scores are derived from the minimal clinical indicators of difference. For example, if a patient deteriorates on one scale (e.g. loses more than 3 points on the RHS scale) but maintains stability or demonstrates improvement on another scale that has been measured since baseline (e.g. RULM), the patient’s treatment with Zolgensma would be considered to be successful. A treating clinician must refer any case to the NHS England Clinical Panel for advice on non-success in respect of deterioration in scale scores.
AND/OR
(b) A deterioration in respiratory function, defined as an increasing requirement for respiratory support overnight and/or, for that patient, an uncharacteristic increase in respiratory infections requiring hospital treatment that cannot be accounted for by aspiration or intrinsic lung disease.
This should be a permanent respiratory deterioration, not one linked to a recurrent infection.
This guidance covers:
- Children who have had Zolgensma only and have not previously been treated with other disease-modifying medicines for SMA
- Children who have had Zolgensma and who have had previous treatment with other disease-modifying medicines for SMA
Children in these two groups can only access other medicines for SMA within the NHS if treatment with Zolgensma is not successful, as defined above AND following advice from the NHS England Clinical Panel. The NHS England Clinical Panel provides expert advice to treatment centres about individual patients in respect of the Starting and Stopping Criteria. Individual treatment centres take decisions about individual patients.
April 2023 Advice:
Having by then considered a number of referrals, NHS England further clarified this definition in a communication to clinicians. NHS England agreed it would be useful for the community to be aware of this and agreed to SMA UK publishing the following:
‘For Zolgensma™ to be agreed as having been unsuccessful, the clinician has to give evidence that the child’s respiratory function meets the criteria outlined below and / or the motor ability criteria, also outlined below.
Respiratory Function
The majority of cases that have been submitted have been put forward on the basis that there has been a deterioration in respiratory function.
The managed access agreement states that a deterioration in respiratory function is defined as:
‘… an increasing requirement for respiratory support overnight and/or, for that patient, an uncharacteristic increase in respiratory infections requiring hospital treatment that cannot be accounted for by aspiration or intrinsic lung disease.’
Following consideration of the cases, the Panel has considered information in detail and has shared the following guidance for clinicians submitting requests:
As set out in ‘A Guide to the 2017 International Standards of Care for SMA’, the use of a cough assist device is a recommended management technique for a child who has a weak cough and is not in itself an indication of deteriorating respiratory function.
As some children have had Zolgensma at an early age and may be in their first winter/year, it is not necessarily feasible to determine if a pattern of respiratory infections and any associated acute need for ventilation is uncharacteristic.
It is not unusual for children with SMA to require ADDITIONAL respiratory support during acute infections. This transient increase in support should be distinguished from cases where there is an enduring need for increased respiratory support.
Motor ability
A treating clinician may refer a child to the clinical panel for further advice if they have:
A total worsening in scale score demonstrated by two consecutive measurements from any two of the following three scales:
- More than 2 points on horizontal kick or 1 point on other HINE scores excluding voluntary grasp.
- More than 4 points on the CHOP INTEND scale.
- More than 3 points on the Revised Hammersmith Scale
A scaled equivalent of these losses would apply if a domain (one of the areas of ability to be measures) was unmeasurable, or not suitable.
These scores are derived from the minimal clinical indicators of difference. For example, if a child deteriorates on one scale (e.g. loses more than 3 points on the RHS scale) but maintains stability or demonstrates improvement on another scale that has been measured since baseline (usually at the start of treatment) – for example the Revised Upper Limb Module (RULM), the child’s treatment with Zolgensma would be considered to be successful. A treating clinician must refer any case to the NHS England Clinical Panel for advice on non- success in respect of deterioration in scale scores.
AND / OR
A deterioration in respiratory function, defined as an increasing requirement for respiratory support overnight and/or, for that patient, an uncharacteristic increase in respiratory infections requiring hospital treatment that cannot be accounted for by aspiration or intrinsic lung disease.’
Q.2. If a family has self-funded treatment with Zolgensma for their child abroad, can they have access to risdiplam (or nusinersen), regardless of their clinical situation?
A.2. The above criteria for access to risdiplam (or nusinersen) following treatment with Zolgensma is based on clinical criteria. It will not be relevant who paid for treatment with Zolgensma but rather how the patient responded to that treatment. This is important as it ensures that patients will not be disadvantaged (or advantaged) because of their economic circumstances and how previous treatment was funded, in line with the NHS constitution.