PegvaliasePALYNZIQ
Treatment of patients aged 16 years and older with hyperphenylalaninemia due to phenylketonuria (PKU) who have inadequate blood phenylalanine control despite prior management with available treatment options.
Decisions on record
- Meeting Mar 2026 Deferred Phenylketonuria (PKU)
- Meeting Jul 2022 Not recommended Phenylketonuria, hyperphenylalaninemia in patients aged 16 years and over not responsive to sapropterin
Access path
- TGA registered · PALYNZIQ
TGA label narrower than the PBS population
- Jul 2022Not recommended
vs phenylalanine-restricted diet alone
- Mar 2026Deferred
Comparator changed: phenylalanine-restricted diet alone → Phe-restricted diet alone
From the public summary
The PBAC did not recommend pegvaliase for the treatment of HPA due to PKU in patients aged 16 years and over who are not responsive to sapropterin. The PBAC considered there was a high clinical need in a small patient population, but that the sponsor’s proposal to restrict use to patients who are not responsive to sapropterin was inequitable and not clinically appropriate.PSD · Jul 2022
The PBAC acknowledged the meaningful consumer support and engagement with regards to the submissions for sapropterin and pegvaliase (Item 6.09, which was also considered at the July 2022 PBAC meeting), including a meeting with patient and health professional representatives held prior to the PBAC meeting.PSD · Jul 2022
The submission presented a cost-utility analysis using a micro-simulation model. This is consistent with the clinical claim.PSD · Jul 2022
The model structure, key inputs and rationale are presented in Table 13. 31PSD · Jul 2022
<360 µmol/L (and in improving ADHD-RS inattention subscale scores from baseline by ≤5) and is inferior in terms of safety.PSD · Jul 2022
The submission described pegvaliase plus a Phe-restricted diet as superior in terms of effectiveness compared with a Phe-restricted diet. The PSCR confirmed that the clinical claim was based on the composite outcome of: a blood-Phe < 360 µmol/L; and/or a ≥ 5-point change from baseline in the ADHD-RS inattention subscale score.PSD · Jul 2022
Representatives of the PBAC met with patient and health professional representatives prior to the PBAC meeting. The following is a summary of the perspectives presented:PSD · Jul 2022
• Diet management alone is extremely difficult and has an enormous impact on patients. Many patients struggle to lower or maintain their Phe levels using diet alone.PSD · Jul 2022
Cost-effectiveness
ICER redacted due to commercial sensitivity. The document states 'The PBAC considered the cost effectiveness was uncertain and the ICER was exceptionally high' with redacted pricing information.
The PBAC considered the cost effectiveness was uncertain and the ICER was exceptionally high at the price proposed. PBAC · 2026
Decision context
PopulationPatients aged 16 years and older with hyperphenylalaninemia due to PKU who have blood phenylalanine levels ≥600 µmol/L and are either not responsive to sapropterin or have daily protein tolerance of less than 15 grams per day.
Risk sharingRisk Sharing Arrangement (RSA) proposed in the resubmission; the document indicates considerable uncertainty regarding the estimated cost which was based on the implementation of the proposed RSA.
Why it was knocked back
- Inadequate clinical evidence demonstrating magnitude of incremental benefit, highly uncertain and uninformative economic model with extrapolations over 100-year time horizon magnifying limitations of clinical data, exceptional ICER relative to accepted comparators, response criteria remain unclear and potentially inconsistent with TGA-approved indication, absence of comparative clinical data for ADHD-RS inattention subscale superiority claim, proposed 24-month initial treatment phase remains inappropriately long, comparator selection does not adequately address sapropterin as a relevant comparator given the broadened patient population
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Mar 2026 | Deferred | Phe-restricted diet alone | — | Single-arm |
| Jul 2022 | Not recommended | phenylalanine-restricted diet alone | — | RCT · Surrogate |
Consumer voice
Patient and health professional representatives reported that diet management alone is extremely difficult with significant impact on patients' quality of life, and that reductions in phenylalanine levels can lead to meaningful improvements in depression, anxiety, working memory, and cognitive function.
Diet management alone is extremely difficult and has an enormous impact on patients. Consumer comments · PSD
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC restricts to sapropterin-failures with baseline phenylalanine ≥600 µmol/L and ≥30% reduction requirement; TGA label has no such criteria.