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Alglucosidase AlfaMyozyme

Not recommended MetabolicNot applicableNot applicable line

Treatment of late-onset Pompe disease in patients with confirmed diagnosis based on enzymology or mutational analysis and clinical features of juvenile or late-onset disease.

8
Submissions
7 resub
2008–13
On the record
$15k–75k
ICER range
5 sourced ICERs · 2008–2013
ICER stated
Cost basis
risk sharing

Decisions on record

6 decisions
  • Meeting Nov 2012 Not recommended Long-term treatment of patients with a confirmed diagnosis of Pompe disease (acid alfa-glucosidase deficiency).
  • Meeting Jul 2011 Deferred Pompe disease
  • Meeting Nov 2010 Not recommended Long-term treatment of patients with a confirmed diagnosis of Pompe disease (acid alfa-glucosidase deficiency).
  • Meeting Nov 2009 Not recommended Long-term treatment of patients with a confirmed diagnosis of Pompe disease (acid alfa-glucosidase deficiency).
  • Meeting Mar 2009 Not recommended Long-term treatment of patients with a confirmed diagnosis of Pompe disease (acid alfa-glucosidase deficiency).
  • Meeting Jul 2008 Not recommended Pompe disease

Access path

8 submissions · public record
  1. TGA registered · Myozyme

    TGA label narrower than the PBS population

  2. Jul 2008
    Not recommended

    Not rejected for PBS Highly Specialised Drug listing; rejected on basis of unacceptably high cost effectiveness.…

  3. Mar 2009
    Not recommended

    unacceptably high cost effectiveness, uncertainty in extrapolating short-term surrogate outcomes (6MWT, FVC) to…

  4. ↻ resubmitted
    Nov 2009
    Recommended
  5. Nov 2010
    Not recommended

    Highly uncertain link between short-term surrogate outcomes (FVC, 6MWT) and patient survival; non-significant…

  6. Jul 2011
    Deferred

    Evidence: RCT, observational studies → RCT | Other (case series, observational study)

  7. Nov 2012
    Recommended

    Evidence: RCT | Other (case series, observational study) → Registry

  8. Nov 2012
    Recommended

    Evidence: RCT | Other (case series, observational study) → Registry

  9. Mar 2013
    Recommended

    Evidence: Registry → Single-arm

  10. PBS listing · Not applicable
RecommendedDeferredNot recommended

From the public summary

Verbatim · PSD text · may span indications
Comparative effectiveness
For PBAC’s views, see Recommendations and Reasons. 10. Economic Analysis The submission presented a trial based economic evaluation in the form of a cost- effectiveness analysis, which was considered valid. The analysis only included Pompe disease in patients less than 26 weeks of age and no economic data for late-onset Pompe disease were presented. Quality of life was not considered.PSD · Jul 2008
The analysis used a time horizon of 52 weeks (date of birth to 52 weeks) i.e 52 weeks of treatment from the first infusion.PSD · Jul 2008

Cost-effectiveness

5 sourced ICERs · 2008–2013

PBAC calculated that at the price proposed, the incremental cost per one life-year gained assuming one year of life extension for four years of treatment was substantially greater than $500,000; if one year gained for eight years of treatment, the incremental cost more than doubled. No formal economic evaluation was presented.

At the price proposed in the submission, based on EMC/IPA survey data, the incremental cost per one life-year gained assuming one year of life extension is gained for four years of treatment was substantially greater than $500, 000. PSD · 2013
ICER uncertain ×2ICER / price too high ×3Economic model disputed ×2Immature survival dataSurrogate endpoint ×2No head-to-head trialIndirect comparison

Decision context

PopulationPatients with a confirmed diagnosis of late-onset Pompe disease based on enzymology or mutational analysis meeting treatment initiation criteria including impaired respiratory function or significant muscular weakness, excluding those who are invasive ventilator dependent, current smokers, or with other severe life-threatening diseases.

Risk sharingPBAC noted that dose escalation circumstances could be managed through a risk-sharing arrangement.

Why it was knocked back

  • unacceptably high incremental cost-effectiveness ratio, insufficient certainty that drug substantially extends lifespan in late-onset Pompe disease, non-randomised observational data subject to residual confounding and unmeasured confounders, heterogeneous late-onset population, modest survival differences compared to infantile-onset disease, price unjustifiably high relative to outcomes

Submission history

8 entries
DecidedOutcomeComparatorICEREvidence
Mar 2013 Recommended standard (palliative) therapy including intensive respiratory support, cardiac care, dietary therapy and rehabilitative $500k Single-arm · OS
Nov 2012 Recommended standard (palliative) therapy including intensive respiratory support, cardiac care, dietary therapy and rehabilitative Registry · OS
Nov 2012 Recommended standard (palliative) therapy including intensive respiratory support, cardiac care, dietary therapy and rehabilitative Registry · OS
Jul 2011 Deferred standard (palliative) therapy including intensive respiratory support, cardiac care, dietary therapy and rehabilitative RCT | Other (case series, observational study) · Other (survival benefit based on FVC and 6MWT improvement, survival data from non-randomised comparison of treated vs untreated patients in the EMC/IPA survey population)
Nov 2010 Not recommended standard (palliative) therapy including intensive respiratory support, cardiac care, dietary therapy and rehabilitative $15k–45k RCT, observational studies · OS | PFS | DFS | ORR | QoL | Surrogate
Nov 2009 Recommended standard (palliative) therapy including intensive respiratory support, cardiac care, dietary therapy and rehabilitative $15k–45k RCT
Mar 2009 Not recommended standard (palliative) therapy including intensive respiratory support, cardiac care, dietary therapy and rehabilitative $15k–45k RCT · 6-minute walk test, percent predicted forced vital capacity
Jul 2008 Not recommended standard (palliative) care $45k–75k RCT, historical control · OS, invasive ventilator-free survival

Similar precedents

By decision profile

Regulatory · TGA

Label narrower than PBS population — PBAC restricted to late-onset disease with specific treatment initiation criteria; TGA label includes all Pompe disease without phenotype or clinical severity restrictions.