Asfotase Alfa Rch
Treatment of juvenile-onset hypophosphatasia (HPP; onset between 6 months and 17 years of age). Asfotase alfa rch is used in combination with best supportive care.
Decisions on record
- Meeting Mar 2018 Not recommended Enzyme replacement therapy in patients with paediatric-onset hypophosphatasia
- Meeting Jul 2017 Not recommended Hypophosphatasia (HPP)
Access path
- Jul 2017Not recommended
vs best supportive care
- Mar 2018Not recommended
Heterogeneity of eligible population introduces significant uncertainty in magnitude of benefit; reliance on secondary…
From the public summary
7.1 The PBAC did not recommend the requested Section 100 (Highly Specialised Drugs Program) listing of asfotase alfa rch for the treatment of patients with juvenile-onset hypophosphatasia (HPP) on the basis of continuing uncertainty about the magnitude of effect in the heterogeneous group of patients proposed in the submission.PSD · Mar 2018
However, the PBAC considered it is likely that there is a group of patients who would derive the most benefit most from treatment with asfotase alfa rch but that it was not possible to identify that group on the basis of the information provided in the current submission.PSD · Mar 2018
6.31 The resubmission presented a modelled cost-utility analysis. While the methodological approach to the model was similar to that presented in the previous submission, it differed with respect to the following aspects: No mortality assumed from HPP due to exclusion of patients with onset of symptoms from 0-6 months of age, no invasive ventilation state, no separate utility value for children less than 5 years of age.PSD · Mar 2018
6.32 Like the previous submission, the health states in the model were defined based on percent predicted 6MWT. This may not be reasonable as the 6MWT was not the primary outcome of the trial or study and no statistically significant differences were observed between groups for this outcome in Trial ENB-009-10 at 24 weeks.PSD · Mar 2018
comparative safety to best supportive care (requires consideration, see below for discussion).PSD · Mar 2018
6.7 All trials and studies were presented in the previous submission. The resubmission reasonably excluded the ENB-002-08 study and extension study ENB-003-08 and studies ENB-010-10 and ENB-011-10 (presented in the previous submission), since these studies did not include any patients with juvenile-onset HPP. 6PSD · Mar 2018
6.2 The PBAC noted and welcomed the input from individuals (55), health care professionals (3) and an organisation (3) via the Consumer Comments facility on the PBS website. The comments described a range of benefits of treatment with asfotase alfa rch for HPP, including reduced pain, reduced disability, delayed disease progression, less fatigue and increased mobility and bone strength.PSD · Mar 2018
6.3 The PBAC noted the advice received from Soft Bones Australia, Soft Bones Canada and Soft Bones USA that considered asfotase alfa rch to be an important medicine in the symptomatic control of HPP. The comments noted the main symptoms reported from HPP patients are pain and fatigue. In particular, it was that noted pain appeared to have the largest effect on mobility.PSD · Mar 2018
Cost-effectiveness
ICER values are redacted (indicated by '''''''' marks in pricing section); economic model exists but numeric ICER not published in public summary
The PBAC considered the heterogeneity of the population who would be eligible under this proposal also contributes significantly to the uncertainty of the magnitude of benefit claimed in the submission. PBAC · 2018
Decision context
PopulationPatients with juvenile-onset hypophosphatasia (onset between 6 months and 17 years of age) with confirmed diagnosis by low alkaline phosphatase activity and HPP-related bone disease on skeletal imaging, and presenting with specified HPP-related morbidities (respiratory compromise, failure to thrive, vitamin B6-dependent seizures, developmental delay, or history of fractures) plus severe functional impairment and chronic musculoskeletal pain
Risk sharingAnnual expenditure cap per patient per year (value redacted) and overall financial cap proposed to year 6 of subsidy
Why it was knocked back
- Heterogeneity of eligible population introduces significant uncertainty in magnitude of benefit; reliance on secondary outcomes with non-significant changes in primary outcome (6MWT distance and quality of life); uncertain utilities based on clinical expert opinion; uncertain costs due to self-administration assumptions; complex proposed restriction requiring further modification; insufficient evidence of superiority in juvenile-onset population aged 6-18 months; small sample size in juvenile-onset subgroup (n=8)
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Mar 2018 | Not recommended | best supportive care (BSC) | — | RCT · 6MWT |
| Jul 2017 | Not recommended | best supportive care | — | RCT · OS |
Consumer voice
Consumer input from 55 individuals, 3 healthcare professionals, and 3 organisations described multiple benefits of asfotase alfa rch for HPP including reduced pain, disability, fatigue, and increased mobility. Soft Bones organizations noted that pain and fatigue are the main symptoms affecting patients, with pain particularly impacting mobility.
The comments described a range of benefits of treatment with asfotase alfa rch for HPP, including reduced pain, reduced disability, delayed disease progression, less fatigue and increased mobility and bone strength. Consumer comments · PSD
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC restricts to juvenile-onset (6 months–17 years) with confirmed diagnosis, bone disease imaging, and specified morbidities; TGA label covers broader paediatric-onset HPP.