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Onasemnogene AbeparvovecZolgensma

Recommended Rare diseaseAuthority RequiredFirst-line line 💬 consumer voice

Pre-symptomatic treatment of babies with spinal muscular atrophy (SMA) and 3 copies of the Survival Motor Neuron 2 (SMN2) gene.

5
Submissions
3 resub
2020–23
On the record
—
ICER range
Cost-min
Cost basis
risk sharing

Decisions on record

6 decisions
  • Meeting Nov 2025 Recommended Spinal muscular atrophy – symptomatic Type I-IIIa and pre-symptomatic SMA with 1-3 SMN2 copies, weighing up to 21 kg no PSD
  • Meeting Jul 2023 Recommended Pre-symptomatic spinal muscular atrophy (SMA)
  • Meeting Nov 2022 Not recommended Spinal muscular atrophy with 3 SMN2 copies (presymptomatic)
  • Meeting Sep 2021 Recommended Spinal muscular atrophy (SMA) Type 1 in paediatric patients aged less than 9 months no PSD
  • Meeting May 2021 Deferred Spinal muscular atrophy Type 1 in paediatric patients no PSD
  • Meeting Nov 2020 Deferred Spinal muscular atrophy (SMA)

Access path

5 submissions · public record
  1. TGA registered · Zolgensma

    TGA label narrower than the PBS population

  2. Nov 2020
    Deferred

    vs nusinersen and best supportive care

  3. May 2021
    Deferred
  4. Sep 2021
    Deferred
  5. Nov 2022
    Not recommended

    Requested substantially higher price not adequately justified given uncertain benefit in population with potentially…

  6. ↻ resubmitted
    Jul 2023
    Recommended

    Comparator changed: usual care / watchful waiting and treat as symptoms appear →…

  7. PBS listing · Authority Required
RecommendedDeferredNot recommended

From the public summary

Verbatim · PSD text · may span indications
PBAC outcome
The PBAC recommended the amendment to the current listing of ONA to include the pre-symptomatic treatment in patients aged up to 9 months, genetically diagnosed SMA, who have a SMN2 gene copy number of 3. The PBAC considered that pre- symptomatic treatment with ONA in patients with 3 copies of SMN2 would provide an additional benefit for some patients compared with initiation of treatment upon development of symptoms.PSD · Jul 2023
The PBAC acknowledged that the current requirement for symptoms to develop prior to accessing subsidised treatment for SMA could have a significant burden on the 27PSD · Jul 2023
Economic analysis
The resubmission presented a cost-minimisation approach which compared ONA for pre-symptomatic patients with 3 copies of SMN2 (the proposed population) with ONA for pre-symptomatic patients with 1-2 copies of SMN2 (as currently listed on the PBS) over a time horizon of two years based on the follow up of SPR1NT (see Table 10).PSD · Jul 2023
The ESC considered the cost minimisation approach presented may not be appropriate as the claim of comparable benefit was not supported by the evidence presented, and given the PBAC has previously considered the incremental benefit of pre-symptomatic treatment with ONA compared to symptomatic treatment with disease modifying therapies for patients with 3 SMN2 copies would be less than that for patients with 1-2 SMN2 copies (paragraph 7.6, ONA PSD, …PSD · Jul 2023
Clinical claim
abeparvovec is non-inferior to the pre-symptomatic treatment of babies with 2 copies of the SMN2 gene with respect to developmental milestones and safety. Source: Table 1.1, p27 of the resubmission.PSD · Jul 2023
ONA= Onasemnogene abeparvovec; SMA=spinal muscular atrophy; SMN=survival motor neuron The resubmission’s clinical claim was that pre-symptomatic treatment of patients with spinal muscular atrophy (SMA) with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene and 3 copies of the SMN2 gene with onasemnogene abeparvovec is non-inferior to the pre-symptomatic treatment of babies with 2 copies of the SMN2 gene with respect to developmental …PSD · Jul 2023
Consumer comments
The PBAC noted that consumer comments on the previous submission emphasised the importance of early intervention in the treatment of SMA in order to prevent irreversible motor neuron loss. The comments noted that while the side effect profile of ONA was not yet completely understood, the treatment demonstrated a favourable safety profile in clinical trials.PSD · Jul 2023
The PBAC noted advice from Spinal Muscular Atrophy Australia on the previous submission strongly supported expanding the current PBS listing of ONA to include the pre-symptomatic treatment of patients genetically diagnosed with SMA who have 3 SMN2 copies.PSD · Jul 2023

Cost-effectiveness

Cost-minimisation analysis presented; no ICER calculated as the submission used a cost-minimisation approach comparing ONA in 3 SMN2 copy patients versus ONA in 2 SMN2 copy patients.

The PBAC agreed with the ESC that as the proportion of patients who would benefit and the magnitude of any benefit are unknown based on the evidence presented, the price requested was not adequately justified. PBAC · 2022
ICER / price too highEconomic model disputed

Decision context

PopulationPaediatric patients less than 9 months of age with spinal muscular atrophy (SMA) with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene and 3 copies of the SMN2 gene.

Risk sharingOutcomes-based Risk Sharing Agreement (RSA) was mentioned in context of the previous September 2021 recommendation for the 1-2 SMN2 copy population.

Why it was knocked back

  • Unclear incremental clinical benefit for patients with 3 SMN2 copies compared to symptomatic treatment with disease-modifying therapies; limited clinical data; cost-minimisation comparison against ONA in 2 SMN2 copy patients was inconsistent with PBAC's previous view; lack of long-term follow-up data; uncertainty regarding subsequent therapy requirements; assumed zero need for follow-on treatment not adequately supported.

Submission history

5 entries
DecidedOutcomeComparatorICEREvidence
Jul 2023 Recommended onasemnogene abeparvovec in patients with 1-2 copies of SMN2 gene — Single-arm · Surrogate
Nov 2022 Not recommended usual care / watchful waiting and treat as symptoms appear — Cost-utility analysis · Milestone developments (standing and walking)
Sep 2021 Deferred nusinersen and best supportive care — Single-arm
May 2021 Deferred nusinersen and best supportive care — Single-arm
Nov 2020 Deferred nusinersen and best supportive care — Single-arm · OS

Clinical evidence

Trials cited in the PSDs · ClinicalTrials.gov
TrialPhaseNPrimary outcomeStatus
SPR1NT Ph 3 30 Cohort 1: Number of Participants Who Achieved Sitting Alone for at Least 30 Seconds completed
STR1VE-US Ph 3 22 Achievement of Independent Sitting for at Least 30 Seconds completed

Consumer voice

Jul 2023

Consumer input emphasized the efficacy of early treatment with ONA in preventing irreversible motor neuron loss and permanent negative outcomes, noting significant benefits for children treated pre-symptomatically including remaining asymptomatic and meeting normal developmental milestones, as well as reduced parental anguish.

Input from consumers noted the efficacy of early treatment with ONA and the negative, permanent impact on outcomes for babies who do not have access to pre-symptomatic treatment. Consumer comments · PSD
early intervention benefitunmet needquality of lifeirreversible motor neuron loss preventiondevelopmental outcomesparental burden

Similar precedents

By decision profile
Nusinersen78%Risdiplam69%Nabiximols62%Asfotase Alfa Rch61%Olipudase Alfa60%Everolimus60%Denosumab59%Omalizumab59%

Regulatory · TGA

Label narrower than PBS population — PBAC restricts to 3 SMN2 copies only; TGA label includes 1-3 copies, encompassing broader genetic eligibility.

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