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FebuxostatAdenuric tablets

Not recommended RheumatologyAuthority RequiredSecond-line line

Treatment of chronic gout in patients with a contraindication to, or intolerant of treatment with allopurinol.

3
Submissions
2 resub
2014–17
On the record
ICER range
Not modelled
Cost basis
risk sharing

Decisions on record

3 decisions
  • Meeting Jul 2017 Not recommended Chronic gout
  • Meeting Mar 2015 Recommended Second-line treatment of chronic symptomatic gout
  • Meeting Mar 2014 Not recommended Adenuric® A.Menarini Australia Pty Ltd Gout To request Authority Required (STREAMLINED) General Schedule listing for the treatment of chronic gouty arthritis associated with hyperuricaemia. Sponsor Comment: Menarini is disappointed by the decision from the PBAC as there is a high clinical need and p

Access path

3 submissions · public record
  1. TGA registered · Adenuric tablets

    TGA label narrower than the PBS population

  2. Mar 2014
    Not recommended

    Clinical data did not demonstrate superior effectiveness to allopurinol for patient-relevant outcomes (reduction in…

  3. ↻ resubmitted
    Mar 2015
    Recommended · restricted

    Comparator changed: allopurinol → probenecid

  4. Jul 2017
    Not recommended

    paucity of evidence of efficacy and safety in allopurinol insufficient patients, risk of prescribing behaviour outside…

RecommendedDeferredNot recommended

From the public summary

Verbatim · PSD text · may span indications
PBAC outcome
5.1 The PBAC did not recommend amending the current Authority Required listing of febuxostat to Authority Required (STREAMLINED) for treatment of chronic gout.PSD · Jul 2017
5.2 The Sponsor presented the utilisation of febuxostat in the first 18 months of listing, and claimed that the number of scripts used was lower than anticipated. The sponsor assumed that the current lower than expected utilisation of the drug was due to the Authority Required restriction.PSD · Jul 2017
Economic analysis
6.19 The economic analysis presented was a cost-per-responder analysis (response defined as achievement of serum uric acid levels <357 µmol/l) of febuxostat compared with placebo and each of the three nominated comparators versus placebo.PSD · Mar 2015
6.20 The economic analysis was a simple decision tree analysis that considered drug treatment costs and the proportion of patients who reached sUA <357 µmol/L (responders). The table below summarises the model structure.PSD · Mar 2015
Clinical claim
6.18 The re-submission appropriately did not make a formal clinical claim regarding the comparative efficacy and safety of febuxostat versus the relevant comparators for any of the populations for whom listing was sought. The re-submission asserted that ≤25% of subjects on allopurinol either cannot tolerate dose titration or cannot achieve sUA ≤357 µmol/L with maximal doses.PSD · Mar 2015
For more detail on PBAC’s view, see section 7 “PBAC outcome”.PSD · Mar 2015
Financial management – risk sharing
6.33 The sponsor signalled its willingness to enter into a risk sharing agreement based on a patient cap and rebate.PSD · Mar 2015

Cost-effectiveness

Not modelled — minor submission requesting streamlined access to existing Authority Required listing; no new economic evaluation undertaken.

The PBAC considered that the advantage of a fast reduction in sUA did not translate into benefits over allopurinol for more clinically meaningful outcomes such as flare reduction, tophi resolution or health-related quality of life (HRQoL). PBAC · 2014
Surrogate endpoint

Decision context

PopulationAdults with chronic gout who have a contraindication to, or are intolerant of, allopurinol.

Risk sharingRisk Sharing Agreement in place to reduce risk of unexpected Commonwealth expenditure if febuxostat used beyond the recommended listing; expenditure cap based on conservative estimate of allopurinol-intolerant patients.

Why it was knocked back

  • paucity of evidence of efficacy and safety in allopurinol insufficient patients, risk of prescribing behaviour outside of current PBS restriction, Authority Required restriction considered appropriate as useful signal regarding appropriate prescribing

Submission history

3 entries
DecidedOutcomeComparatorICEREvidence
Jul 2017 Not recommended probenecid Not applicable
Mar 2015 Recommended · restricted probenecid RCT · Serum uric acid reduction
Mar 2014 Not recommended allopurinol RCT · Surrogate

Clinical evidence

Trials cited in the PSDs · ClinicalTrials.gov
TrialPhaseNPrimary outcomeStatus
APEX Ph 3 1,072 Percentage of Subjects Whose Last Three Serum Urate Levels Are <6.0 Milligram Per Decilite… completed
FACT Ph 3 760 Percentage of Subjects With the Last 3 Serum Urate Levels <6.0 Milligrams Per Deciliter (m… completed
EXCEL Ph 3 1,086 Percentage of Subjects Whose Serum Urate Level Decreases to < 6.0 mg/dL at Month 1. completed
CONFIRMS Ph 3 2,269 Percentage of Subjects Whose Serum Urate Level is <6.0 Milligrams Per Deciliter (mg/dL) at… completed
FOCUS Ph 2 116 Percentage of Subjects Whose Serum Urate Level Decreases to or is Maintained at <6.0 mg/dL… completed

Similar precedents

By decision profile

Regulatory · TGA

Label narrower than PBS population — PBAC restricts to allopurinol-intolerant/contraindicated patients; TGA label has no such treatment-history prerequisite.