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Sodium PhenylbutyratePHEBURANE

Recommended MetabolicAuthority RequiredFirst-line line 💬 consumer voice

Chronic treatment of patients with urea cycle disorders (UCD) presenting with elevated ammonia levels not controlled with diet alone and other adjunct care alone.

4
Submissions
3 resub
2017–19
On the record
ICER range
Cost-min
Cost basis

Decisions on record

5 decisions
  • Meeting Jul 2019 Recommended Urea cycle disorder (UCD)
  • Meeting Mar 2019 Not recommended SODIUM PHENYLBUTYRATE is indicated for the management of hyperammonaemia associated with urea cycle disorders (UCD).
  • Meeting Mar 2019 Not recommended Indication not stated
  • Meeting Mar 2018 Not recommended Indicated for the management of hyperammonaemia associated with urea cycle disorders. Pheburane® should be used with dietary protein restriction and, in some cases, dietary supplements (e.g. essential amino acids, arginine, citrulline, and protein-free calorie supplements)
  • Meeting Nov 2017 Not recommended Urea cycle disorder (UCD)

Access path

4 submissions · public record
  1. TGA registered · PHEBURANE

    TGA label narrower than the PBS population

  2. Nov 2017
    Recommended · restricted

    vs Standard care comprising uncoated sodium phenylbutyrate…

  3. Mar 2018
    Not recommended

    Comparator changed: Standard care comprising uncoated sodium phenylbutyrate and/or sodium…

  4. Mar 2019
    Not recommended

    Comparator changed: uncoated sodium phenylbutyrate powder compounded into oral suspension…

  5. ↻ resubmitted
    Jul 2019
    Recommended · restricted

    Comparator changed: uncoated sodium phenylbutyrate (compounded into oral suspension or…

  6. PBS listing · Authority Required
RecommendedDeferredNot recommended

From the public summary

Verbatim · PSD text · may span indications
PBAC outcome
7.1 The PBAC recommended the Authority Required (STREAMLINED) listing of a sugar- coated granule formulation of sodium phenylbutyrate (referred to as coated NaPb) for the chronic treatment of patients with urea cycle disorders (UCD).PSD · Jul 2019
7.2 The PBAC noted that the resubmission had proposed a revised maximum quantity of three bottles per prescription and considered this appropriate for providing sufficient supply for a month for most patients.PSD · Jul 2019
Economic analysis
6.4 No formal cost-minimisation analysis was presented. The proposed price was consistent with the PBAC’s previous advice that the NaPb price should be “no higher than $''''''' per 84 g bottle of coated NaPb” (March 2019 PBAC Minutes, paragraph 7.10).PSD · Jul 2019
Clinical claim
6.10 The resubmission claimed coated NaPb was non-inferior in terms of efficacy and safety compared to uncoated NaPb (for patients who were intolerant to or inadequately controlled by NaBz or requiring combination therapy).PSD · Mar 2019
6.11 The evaluation and the ESC considered that the non-inferiority claim of coated NaPb compared with uncoated NaPb was reasonable when the line of therapy was not specified, since the PBAC has previously accepted the claim based on similar evidence.PSD · Mar 2019
Consumer comments
6.2 The PBAC noted and welcomed the input from a paediatrician via the Consumer Comments facility on the PBS website. The comment outlined that, in current clinical practice, NaBz is used as first line treatment for urea cycle disorders, with the addition of NaPb if required. The clinician considered that NaPb would not replace NaBz.PSD · Mar 2019

Cost-effectiveness

Cost-minimisation analysis; no numeric ICER calculated. The submission was cost-minimisation based, comparing against compounded sodium benzoate.

Economic model disputed ×2Surrogate endpointNo head-to-head trial

Decision context

PopulationPatients with urea cycle disorders requiring ammonia scavenger therapy, with elevated ammonia levels not controlled with diet alone and other adjunct care alone.

Submission history

4 entries
DecidedOutcomeComparatorICEREvidence
Jul 2019 Recommended · restricted sodium benzoate (NaBz) Cost-minimisation · Cost-minimisation
Mar 2019 Not recommended uncoated sodium phenylbutyrate (compounded into oral suspension or capsules) Single-arm · Surrogate
Mar 2018 Not recommended uncoated sodium phenylbutyrate powder compounded into oral suspension or capsules by a compounding pharmacy Cost-minimisation · Cost-minimisation
Nov 2017 Recommended · restricted Standard care comprising uncoated sodium phenylbutyrate and/or sodium benzoate; natural history (no ammonia scavengers) Single-arm · Hyperammonemic episodes, neurocognitive outcomes, survival

Consumer voice

Mar 2019

A paediatrician and the Metabolic Dietary Disorders Association provided input emphasizing that NaPb is used alongside NaBz (not as replacement) in urea cycle disorder treatment, and highlighted significant palatability issues with uncoated formulations that affect patient compliance, with coated preparations offering improvement.

NaPb would not replace NaBz. Consumer comments · PSD
treatment burdenpatient compliancepalatabilityunmet need

Similar precedents

By decision profile

Regulatory · TGA

Label narrower than PBS population — PBAC restricts to elevated ammonia not controlled with diet and adjunct care alone; TGA label does not specify this treatment-failure criterion.