Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Risdiplam shows moderate benefit over current care, particularly in improving motor function in SMA types 1 to 3. The evidence from the SUNFISH and FIREFISH trials indicates significant improvements in motor function scores, although the long-term benefits remain uncertain due to the lack of Phase 3 evidence. The committee noted that while there is some evidence suggesting improved survival for type 1 SMA, the absence of direct comparative evidence against usual care limits the strength of the claim.
Cost effectiveness
The cost-effectiveness estimates for risdiplam are above the thresholds typically considered acceptable by NICE, particularly for type 1 SMA where the ICER exceeds £50,000 per QALY. Although the company proposed a managed access agreement to collect further data, the current economic model does not sufficiently justify the high costs associated with the treatment.
Quality of life
The evidence indicates modest improvements in HRQoL for patients using risdiplam, particularly in motor function and independence. Patient experts reported that even small improvements in motor skills significantly enhance quality of life. However, the evidence is primarily derived from indirect measures and lacks robust HRQoL data directly linked to risdiplam.
Supporting Domains
Safety and Adverse Effects
Risdiplam has a very good safety profile with mostly mild to moderate adverse events reported. Serious adverse events are rare, and the overall tolerability is acceptable. The committee noted that the safety data from the clinical trials supports its use, although ongoing monitoring is necessary.
Comparator Selection
The primary comparator for risdiplam is best supportive care, which is appropriate given the context of SMA treatment. However, the lack of direct evidence comparing risdiplam with other disease-modifying treatments like nusinersen limits the robustness of the evidence. The committee acknowledged that while best supportive care is commonly used, the absence of direct comparisons is a notable gap.
Patient Population and Subgroups
The trial populations for risdiplam are broadly representative of the SMA patient population in the Healthcare, covering types 1 to 3. The committee noted that while there are some limitations in subgroup analyses, the overall population included in the studies reflects the intended use of the treatment.
Care Pathway Integration
Risdiplam can be integrated into existing care pathways with minor adjustments, as it is an oral treatment that does not require invasive procedures like lumbar punctures. The committee recognized that this ease of administration is a significant advantage over existing treatments.
Resource Use and Cost Implications
The resource implications of adopting risdiplam are notable, with concerns about the overall budget impact on the Healthcare. The committee highlighted that while the managed access agreement may mitigate some financial risks, the high costs associated with the treatment raise concerns about sustainability.
Evidence Quality and Robustness
The evidence base for risdiplam includes data from Phase 2 trials, which, while informative, do not provide the same level of robustness as Phase 3 trials. The committee noted gaps in evidence and potential biases, particularly regarding long-term outcomes and indirect comparisons.
Uncertainty, Sensitivity, and Broader Impacts
There is significant uncertainty regarding the long-term benefits of risdiplam, particularly for type 1 SMA. The committee acknowledged that while there is a managed access agreement in place to collect further data, the current uncertainties may limit the treatment’s broader acceptance and use.
