Olipudase AlfaXenpozyme
Treatment of acid sphingomyelinase deficiency (ASMD) type A/B or type B in paediatric and adult patients. Olipudase alfa is an enzyme replacement therapy indicated for non-central nervous system manifestations of ASMD.
Decision on record
- Meeting Jul 2023 Not recommended Acid sphingomyelinase deficiency (ASMD)
Access path
- TGA registered · Xenpozyme
TGA label narrower than the PBS population
- Jul 2023Not recommended
vs best supportive care (placebo)
From the public summary
The PBAC did not recommend the Section 100 (Highly Specialised Drugs Program) listing of olipudase alfa for the treatment of acid sphingomyelinase (ASMD) type A/B or type B. The PBAC considered olipudase alfa was an effective treatment for ASMD type A/B or type B; however, the incremental cost effectiveness ratio (ICER) for olipudase alfa compared to best supportive care was extremely high and uncertain.PSD · Jul 2023
The PBAC considered the primary reason for this outcome was due to the economic evaluation provided.PSD · Jul 2023
The submission presented two separate cost-utility analyses comparing olipudase alfa and BSC for the treatment of ASMD type A/B or type B in (i) adult and (ii) paediatric populations. A summary of the model structure in the submission’s economic evaluation is presented in Table 13. 30PSD · Jul 2023
Transition probabilities for paediatric patients were calculated using ASCEND-peds for olipudase alfa and SPHINGO-100 to for BSC. In subsequent years, probabilities for olipudase alfa arm were Transition probabilities calculated using a combination of patients from ASCEND-peds who transitioned to the long-term (Paediatric population) study, while SPHINGO-100 was used for BSC.PSD · Jul 2023
The submission described olipudase alfa as superior in terms of effectiveness compared to BSC. This claim was adequately supported by evidence, but the following issues need to be considered:PSD · Jul 2023
The PBAC agreed with the ESC and the evaluation, that olipudase alfa has superior effectiveness compared to BSC in terms of the change spleen volume and DLco, which are both clinically relevant to ASMD; however, it is uncertain whether it would translate into an overall survival (OS) benefit over the long-term.PSD · Jul 2023
The health care professionals commented on the favourable clinical trial results with respect to improvements in lung function, organ size and blood counts. Olipudase alfa treatment was reported to result in general quality of life improvements with respect to energy and well-being, with an expectation that treatment early in the disease course would allow a nearly normal life, largely free of disease manifestations.PSD · Jul 2023
The individuals who commented comprised an ASMD patient, a parent/partner of an ASMD patient, and one other interested individual. The comments noted the declining quality of life for the patient requiring oxygen, and the anticipated improvement upon treatment with olipudase alfa and the manageable side effects. The comments also described the social, financial and mental impact of living with ASMD without effective 8PSD · Jul 2023
Cost-effectiveness
ICER values not stated in the public summary document provided; economic evaluation section is incomplete in the extracted text.
The PBAC considered that extending the superior findings for spleen volume and DLco to a survival benefit was uncertain. PBAC · 2023
Decision context
PopulationAdult and paediatric patients with ASMD type A/B or type B with confirmed acid sphingomyelinase deficiency and at least one clinical finding including splenomegaly (≥6 multiples normal for adults, ≥5 for children), symptomatic organomegaly, interstitial lung disease, elevated liver enzymes >2× ULN, hypersplenism, or growth delay in children.
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Jul 2023 | Not recommended | best supportive care (placebo) | — | RCT · Surrogate |
Clinical evidence
| Trial | Phase | N | Primary outcome | Status |
|---|---|---|---|---|
| ASCEND | Ph 2, PHASE3 | 36 | Percent Predicted (% Predicted) Hemoglobin (Hb) and Altitude-Adjusted Diffusing Capacity o… | completed |
Consumer voice
Health care professionals highlighted favourable clinical trial results and transformative quality of life improvements with early treatment, though noted burden of lifelong fortnightly infusions. Individual patients and carers described declining quality of life, anticipated treatment benefits, and manageable side effects, alongside social, financial and mental impacts of living with ASMD.
Olipudase alfa treatment was reported to result in general quality of life improvements with respect to energy and well-being, with an expectation that treatment early in the disease course would allow a nearly normal life, largely free of disease manifestations. Consumer comments · PSD
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC restricts to confirmed ASMD with specific clinical findings (splenomegaly, organomegaly, lung disease, etc.); TGA label has no such clinical severity criteria.