Nusinersen
Initial treatment of pre-symptomatic spinal muscular atrophy (SMA) in individuals with SMN1 deletion or mutation and 3 copies of the SMN2 gene, aged less than 18 years.
Decisions on record
- Meeting Dec 2025 Recommended Spinal muscular atrophy (SMA) no PSD
- Meeting Jul 2023 Recommended Pre-symptomatic spinal muscular atrophy (SMA)
- Meeting Mar 2022 Recommended Spinal muscular atrophy
- Meeting Jul 2021 Not recommended Spinal muscular atrophy
- Meeting Jul 2021 Recommended Type IIIb paediatric spinal muscular atrophy
- Meeting Nov 2020 Not recommended Nusinersen is indicated for the treatment of 5q Spinal Muscular Atrophy (SMA)
- Meeting Jul 2020 Recommended Spinal muscular atrophy (SMA)
- Meeting Nov 2019 Not recommended Spinal muscular atrophy (SMA) no PSD
3 earlier decisions
- Jul 2019 Deferred Spinal muscular atrophy (SMA)
- Mar 2018 Recommended Treatment of infantile- onset (Type I) spinal muscular atrophy (SMA)
- Nov 2017 Not recommended Spinal muscular atrophy (SMA)
Access path
- Nov 2017Not recommended
vs placebo and continuation of standard care
- ↻ resubmittedMar 2018Recommended · restricted
Comparator changed: placebo and continuation of standard care → standard of care
- Jul 2018Recommended · restricted
Evidence: RCT → Other
- Jul 2019Not recommended
clinical claim not supported by data presented (non-randomised, non-controlled trial with no comparator arm; unreliable…
- Jul 2019Deferred
Evidence: Other → Single-arm
- Jul 2020Recommended · restricted
Comparator changed: symptomatic treatment with nusinersen (standard of care) →…
- Nov 2020Not recommended
Comparator changed: symptomatic initiation of treatment with nusinersen → standard of…
- ↻ resubmittedJul 2021Recommended · restricted
Comparator changed: standard of care (natural history of SMA with standard of care) →…
- Mar 2022Recommended · restricted
Comparator changed: standard of care (for no treatment) → standard of care (natural…
- Jul 2023Recommended · restricted
Comparator changed: standard of care (natural history of SMA with standard of care) →…
- PBS listing · Authority Required
From the public summary
The PBAC recommended the amendment to the current listing of nusinersen to include the pre-symptomatic initiation of nusinersen in patients aged less than 36 months, genetically diagnosed with spinal muscular atrophy (SMA), who have a survival motor neuron 2 (SMN2) gene copy number of 3.PSD · Jul 2023
The PBAC did not recommend expanding the listing for pre-symptomatic initiation of nusinersen to patients aged from 36 months to under 18 years of age. The PBAC noted no evidence was provided to support expansion of the pre-symptomatic listing to patients in this age group and considered there is likely to be few, if any, genetically diagnosed pre-symptomatic patients aged > 36 months.PSD · Jul 2023
The resubmission presented a modelled cost-utility analysis that was largely based assumptions made by the sponsor. No data from the clinical evaluation was included in the model.PSD · Jul 2023
Table 12 provides a summary the key components of the economic evaluation.PSD · Jul 2023
The resubmission concluded that in individuals with pre-symptomatic SMA withPSD · Jul 2023
3 SMN2 copies, nusinersen is clinically superior in terms of comparative effectiveness and no worse in terms of comparative safety, compared to treatment with nusinersen upon symptom onset in the same population.PSD · Jul 2023
These comments were consistent with the clinician’s comments provided in the sponsor hearing. The report made the following recommendations:PSD · Mar 2022
• Treatment effectiveness should be determined using information from a combination of validated physical assessments, patient reported outcome measures and consultation between the adult living with SMA and the neuromuscular specialist. Effectiveness can be defined as improvement, stabilisation or minimal decline in symptoms over 2 years.PSD · Mar 2022
Cost-effectiveness
ICER values are redacted (commercial-in-confidence). The PSD states the economic model was updated but does not publish numeric ICER figures in the public document.
The model was considered overly simplistic and likely to be unfit for purpose as there were no health states considered and no changes in QALYs over time (except for discounting at 5%). PSD · 2019
Decision context
PopulationPre-symptomatic individuals with genetically confirmed 5q SMA (SMN1 deletion or mutation) with 3 copies of the SMN2 gene, aged less than 18 years, untreated with gene therapy.
Risk sharingA rebate was proposed for individuals with pre-symptomatic SMA with 3 SMN2 copies, aligned with the special pricing arrangement (SPA) currently applied in the symptomatic setting.
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Jul 2023 | Recommended · restricted | nusinersen upon symptom onset (symptomatic treatment) | — | Single-arm · Time to death or respiratory intervention |
| Mar 2022 | Recommended · restricted | standard of care (natural history of SMA with standard of care) | — | Registry · Other |
| Jul 2021 | Recommended · restricted | standard of care (for no treatment) | — | Single-arm · Motor function (HFMSE, RULM, 6MWT) and respiratory function (FVC, peak cough flow) |
| Nov 2020 | Not recommended | standard of care (natural history of SMA with standard of care) | — | Single-arm · Change from baseline in HFMSE score |
| Jul 2020 | Recommended · restricted | symptomatic initiation of treatment with nusinersen | — | RCT · Time to death or respiratory intervention |
| Jul 2019 | Not recommended | symptomatic treatment with nusinersen (standard of care) | — | Single-arm · Time to death or respiratory intervention; Survival and Motor function |
| Jul 2019 | Deferred | symptomatic treatment with nusinersen (standard of care) | — | Single-arm |
| Jul 2018 | Recommended · restricted | — | — | Other |
| Mar 2018 | Recommended · restricted | standard of care | — | RCT · EFS |
| Nov 2017 | Not recommended | placebo and continuation of standard care | — | RCT · Event-free survival (Type I); HFMSE change from baseline (Type II) |
Clinical evidence
| Trial | Phase | N | Primary outcome | Status |
|---|---|---|---|---|
| NURTURE | Ph 2 | 25 | Time to Death or Respiratory Intervention | completed |
| ENDEAR | Ph 3 | 122 | Percentage of Motor Milestones Responders | terminated |
| CHERISH | Ph 3 | 126 | Change From Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE) Score at Mon… | completed |
| SHINE | Ph 3 | 292 | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Ev… | completed |
Codependent tests
| Service | Biomarker | MSAC outcome | Year |
|---|---|---|---|
| SMN2 copy number testing for spinal muscular atrophy severity prediction in pre-symptomatic patients | SMN2 copy number | supported with conditions | 2019 |
Consumer voice
Consumer input emphasized the importance of early diagnosis and treatment of SMA, with the National Paediatric Medicines Forum supporting PBS listing of nusinersen for patients with 3 SMN2 copies to improve equitable access, reduce family anguish, and prevent irreversible motor neuron degeneration in newly diagnosed infants.
The comments emphasised the importance of early diagnosis and treatment of SMA, including the potential for improved motor function in children with SMA who undergo early intervention. Consumer comments · PSD
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC restricts to pre-symptomatic, age <18, SMN2=3 copies, untreated; TGA label covers all 5q SMA regardless of stage or prior treatment.