Sapropterin
Extension of current PBS listing for hyperphenylalaninemia (HPA) due to phenylketonuria (PKU) to allow adults aged ≥18 years to be eligible for sapropterin responsiveness testing and continuing treatment for those who are sapropterin responsive.
Decisions on record
- Meeting Jul 2022 Recommended Phenylketonuria, hyperphenylalaninemia in adult patients
- Meeting Dec 2020 Recommended Maternal phenylketonuria (MPKU) no PSD
- Meeting Nov 2020 Deferred Maternal phenylketonuria (MPKU)
- Meeting Jul 2019 Recommended Hyperphenylalaninaemia (HPA)
- Meeting Nov 2018 Recommended Hyperphenylalaninemia (HPA)
- Meeting Mar 2018 Deferred Hyperphenylalaninaemia (HPA)
- Meeting Nov 2012 Recommended Hyperphenylalaninaemia
- Meeting Jul 2012 Not recommended Treatment of hyperphenylalaninaemia (HPA) in sapropterin-responsive adult and paediatric patients with phenylketonuria (PKU) or tetrahydrobiopterin (BH4) deficiency.
1 earlier decision
- Nov 2011 Not recommended Treatment of elevated phenylalanine blood levels (rare metabolic disorder)
Access path
- Jul 2012Recommended
Comparator changed: prior treatment with sapropterin → prior treatment with sapropterin…
- Jul 2012Noted
Comparator changed: prior treatment with sapropterin → prior treatment with sapropterin…
- Nov 2012Not recommended
uncertain benefit in adult and elderly patients, low-quality and limited clinical evidence, uncertain…
- Mar 2018Deferred
Comparator changed: prior treatment with sapropterin → Placebo plus relaxed/abandoned…
- Nov 2018Recommended · restricted
Comparator changed: Placebo plus relaxed/abandoned phenylalanine-restricted diet (poorly…
- Jul 2019Recommended · restricted
Evidence: RCT → Other
- Dec 2020Recommended · restricted
- Jul 2022Recommended
Comparator changed: Phenylalanine-restricted diet → phenylalanine (Phe)-restricted diet
- PBS listing · Restricted
From the public summary
The PBAC recommended the listing of sapropterin for initiation in adult patients with HPA due to PKU. The PBAC was satisfied that sapropterin provides, for some patients, a significant improvement in efficacy over a Phe-restricted diet alone. The PBAC considered there was a high clinical need in a small patient population.PSD · Jul 2022
The PBAC acknowledged the meaningful consumer support and engagement with regards to the submissions for sapropterin and pegvaliase (Item 5.09, which was also considered at the July 2022 PBAC meeting), including a meeting with patient and 33PSD · Jul 2022
(paras 7.12-13, March 2018 PSD) Financials/ Revised RSA was required based on updated Updated Financials and RSA financial estimates. (para 7.17, March 2018 PSD) RSA Source: Sapropterin March 2018 PSD and Sapropterin November 2018 PSD The maternal PKU November 2020 PSD also included PBAC considerations relevant to the current submission. These are presented in Table 3. 3PSD · Jul 2022
The PBAC considered the clinical benefits of reductions in maternal Phe levels are potentially greater than for the overall PKU population, and more closely In the MPKU population, resemble the benefits achieved for patients aged under 18 years.PSD · Jul 2022
Sapropterin has non-inferior safety compared with a Phe-restricted diet alone. Source: Table 1.1-1, p5 of the submission. 1PSD · Jul 2022
The submission described sapropterin as superior in terms of effectiveness compared with a Phe-restricted diet alone and non-inferior in terms of safety compared to a Phe-restricted diet alone.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 previously estimated at >$200,000/QALY in March 2018 submission for patients aged ≥18 years, considered unacceptably high. Current submission's economic model outcome not explicitly stated in the PSD text provided.
The PBAC noted that sapropterin is currently subject to separate RSAs encompassing subsidisation caps for each indication (HPA due to BH4 deficiency and HPA due to PKU). PBAC · 2019
Decision context
PopulationAdults aged ≥18 years with hyperphenylalaninemia (HPA) due to phenylketonuria (PKU) who are sapropterin responsive, with baseline blood phenylalanine level >600 micromole per L.
Risk sharingSpecial pricing arrangements apply to sapropterin listing as noted in the requested listing table.
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Jul 2022 | Recommended | phenylalanine (Phe)-restricted diet | — | RCT · Reduction in blood phenylalanine levels by >30% from sapropterin-naïve baseline |
| Dec 2020 | Recommended · restricted | Phenylalanine-restricted diet | — | Other · Surrogate |
| Jul 2019 | Recommended · restricted | — | — | Other |
| Nov 2018 | Recommended · restricted | strict / relaxed / abandoned phenylalanine (Phe)-restricted diet and Phe-free supplements | — | RCT · Surrogate |
| Mar 2018 | Deferred | Placebo plus relaxed/abandoned phenylalanine-restricted diet (poorly controlled Phe levels); strict phenylalanine-restri | — | RCT · Change in blood phenylalanine levels (poorly controlled); change in dietary restrictions/phenylalanine intake (well controlled) |
| Nov 2012 | Not recommended | prior treatment with sapropterin | $45k–75k | Registry |
| Jul 2012 | Recommended | prior treatment with sapropterin | $45k–75k | case studies |
| Jul 2012 | Noted | prior treatment with sapropterin; synthetic BH4 | $45k–75k | Single-arm |
Clinical evidence
| Trial | Phase | N | Primary outcome | Status |
|---|---|---|---|---|
| PKU-001 | NA | — | Neuroimaging biomarkers | withdrawn |
| PKU-006 | Ph 3 | 111 | Tabulation of the Incidence and Frequency of All AEs and SAEs That Occur Throughout the St… | completed |
| PKU-015 | Ph 3 | 95 | Full-Scale Intelligence Quotient (FSIQ) Score | completed |
| SPARK | Ph 3 | 56 | Dietary Phenylalanine (Phe) Tolerance at Week 26 | completed |
| KOGNITO | Ph 4 | 34 | Mean Full Scale Intelligence Quotient (FSIQ) Score of the Wechsler Intelligence Scale for … | completed |
| ENDURE | Ph 4 | 59 | Percentage of Participants With at Least 30 Percent Reduction From Baseline in Blood Pheny… | completed |
Consumer voice
Patient and health professional representatives highlighted the significant burden of diet management alone in controlling Phe levels, and the substantial cognitive and psychiatric benefits that can result from reductions in Phe levels in adults. They also indicated that positioning pegvaliase as second-line after sapropterin was inappropriate.
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. Consumer comments · PSD
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC restricts to adults ≥18 years with sapropterin responsiveness and baseline phenylalanine >600 micromole/L; TGA label includes all responsive pediatric and adult patients.