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
7.1 The PBAC deferred making a recommendation regarding pegvaliase for the treatment of patients with phenylketonuria (PKU) who have inadequate blood phenylalanine (Phe) control despite prior management with available treatment options including a Phe restricted diet and sapropterin. The PBAC was satisfied that pegvaliase provides, for some patients, a significant improvement in efficacy over a Phe-restricted diet alone.PSD · Mar 2026
7.2 The PBAC welcomed input from individuals and the Metabolic Dietary Disorders Association. The input described the challenges of living with PKU including the severe and lifelong burden of dietary restrictions. The input also outlined the cognitive impacts of high Phe levels including difficulty concentrating, reduced mental clarity, anxiety and fatigue. The input described current treatments as often 57 OFFICIALPSD · Mar 2026
6.44 The resubmission presented a stepped cost-utility analysis using a micro-simulation model to compare pegvaliase with a Phe restricted diet versus a Phe-restricted diet.PSD · Mar 2026
While this was consistent with the clinical claim, the model did not incorporate the proposed population of patients with PKU aged 16 years and over who are responders to sapropterin and have a daily protein tolerance of less than 15 grams.PSD · Mar 2026
6.37 The evaluation considered that the following key issues, which were raised for the previous submission, remain applicable to the resubmission:PSD · Mar 2026
• The ESC previously considered that it was not possible to quantify the magnitude of the incremental benefit based on the evidence provided given the limitations in the methodology of both comparisons and the poor quality of the evidence underpinning these comparisons (e.g., the high risk of bias in the studies and the lack of detailed information about the flow of patients through PKUDOS). (paragraph 6.52, pegvaliase PSD, July 2022 PBAC meeting).PSD · Mar 2026
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 | $655k–755k | 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.