Carglumic AcidCarbaglu
Treatment of acute hyperammonaemia due to organic acidaemias (isovaleric acidaemia, methylmalonic acidaemia, and propionic acidaemia).
Decision on record
- Meeting Jul 2015 Not recommended Hyperammonaemia
Access path
- TGA registered · Carbaglu
TGA label narrower than the PBS population
- Jul 2015Not recommended
unclear clinical need for PBS listing given uncertainty about use outside hospital admission, clinical claim not…
From the public summary
7.1 The PBAC rejected the request to list carglumic acid on the PBS for the treatment of hyperammonaemia on the basis that it considered that the PBS was not the appropriate mechanism for dispensing carglumic acid, in light of advice provided by the ASIEM.PSD · Jul 2015
7.2 The PBAC noted the ASIEM advice that carglumic acid has only been used in the setting of hospital admission, and considered that the provision of carglumic acid to neonates and older children would constitute routine care provided by hospitals in the context of acute decompensation episodes. In this regard, the PBAC considered that there was no unmet clinical need to be addressed through listing carglumic acid on the PBS.PSD · Jul 2015
6.7 The PSCR noted that the rarity of the organic acidaemia conditions make the running of suitably powered randomised clinical trials very difficult. The ESC acknowledged the challenges regarding the availability of reliable data in the context of such a rare condition.PSD · Jul 2015
6.18 The submission presented a simple cost-effectiveness analysis based on carglumic acid drug costs per episode (see Table 4). The results are summarised in Table 5. 8PSD · Jul 2015
6.15 The submission described carglumic acid as having superior long-term efficacy when added to current standard of care (a low protein or protein-free diet, high calorie nutrition, arginine supplementation, ammonia scavengers and haemofiltration as rescue therapy), and is well tolerated with no reports of significant adverse effects to the drug.PSD · Jul 2015
However, only two patients (both reported by Camozzi 2009) were older than 10 years of age, with the mean age of all patients being less than one year in all studies. Noting the lack of data in adults, the ESC noted that it was unclear if patients would continue to have decompensation episodes as they get older.PSD · Jul 2015
6.29 The submission stated that the sponsor was willing to undertake a risk sharing arrangement. No further details were provided.PSD · Jul 2015
For more detail on PBAC’s view, see section 7 “PBAC outcome”PSD · Jul 2015
Cost-effectiveness
Economic evaluation presented but ICER not explicitly stated in the public text; document indicates cost-effectiveness analysis was conducted but specific numeric ICER values are not disclosed in this PSD.
A cost-effectiveness analysis for carglumic acid versus standard therapy in acute hyperammonaemia secondary to IVA, MMA or PA was presented. PSD · 2015
Decision context
PopulationNeonates and young children with acute hyperammonaemia secondary to organic acidaemias (isovaleric acidaemia, methylmalonic acidaemia, or propionic acidaemia), typically in hospital or intensive care settings.
Why it was knocked back
- unclear clinical need for PBS listing given uncertainty about use outside hospital admission, clinical claim not adequately supported by case report evidence lacking control group, surrogate endpoint (plasma ammonia reduction) relationship to patient-relevant outcomes unclear, small patient numbers with high risk of bias and confounding factors not accounted for
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Jul 2015 | Not recommended | placebo or standard care without carglumic acid | — | Single-arm · Surrogate |
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC restricts to acute hyperammonaemia in organic acidaemias only, excluding NAGS deficiency covered by TGA label.