IcatibantCIPLA ICATIBANT
Symptomatic treatment of acute attacks of hereditary angioedema (HAE) in adults with C1-esterase inhibitor deficiency.
Decisions on record
- Meeting Jul 2017 Recommended Hereditary angioedema
- Meeting Nov 2016 Not recommended Hereditary angioedema
- Meeting Mar 2012 Recommended Hereditary angioedema no PSD
- Meeting Nov 2011 Deferred Acute hereditary angioedema no PSD
- Meeting Jul 2011 Not recommended For symptomatic treatment of acute attacks of hereditary angioedema (HAE) in adults (with C1-esterase-inhibitor deficiency).
- Meeting Jul 2010 Not recommended Acute hereditary angioedema
Access path
- TGA registered · CIPLA ICATIBANT
TGA label narrower than the PBS population
- Jul 2010Not recommended
Insufficient evidence to support non-inferiority claim against C1-INH (no direct trials, heterogeneous indirect…
- Jul 2010Not recommended
Insufficient evidence in the proposed self-administration setting, uncertain comparative effectiveness versus C1-INH…
- Jul 2011Not recommended
uncertain applicability of hospital trial data to self-administration setting, lack of randomised evidence in…
- Nov 2016Not recommended
ICER rose $75,000 → $105,000 (+40%)
- ↻ resubmittedJul 2017Recommended
Evidence: RCT → Other
- PBS listing · Authority Required
From the public summary
4.1 The PBAC recommended limiting increases in the maximum quantity to 12 injections per authority prescription on the basis that this would encourage further clinical review of patients experiencing a high frequency of attacks.PSD · Jul 2017
4.2 The PBAC recommended that the current restrictions for icatibant include a prescribing instruction stating that ‘Increased maximum quantities will be limited to 12 injections per authority prescription’.PSD · Jul 2017
6.13 The submission presented an updated cost-utility analysis and conducted two analyses of the economic model: a Markov cohort analysis and a microsimulation analysis. 8PSD · Nov 2016
Methods used to generate Cohort expected value analysis. results Microsimulation with distribution of treated attack frequency. The inclusion of the microsimulation analysis is purely to allow an estimate of the effect on the incremental cost effectiveness of varying attack frequency. This could have been achieved within the cohort model structure.PSD · Nov 2016
6.9 Icatibant is described as superior in terms of comparative effectiveness and inferior in terms of comparative safety over placebo. This is unchanged from the July 2011 submission.PSD · Nov 2016
6.10 The PBAC previously recommended that, on the basis of the clinical trials, icatibant was superior in terms of efficacy over placebo (July 2011). However, at that time the PBAC noted that the applicability of the trial results to the requested PBAC population remained uncertain.PSD · Nov 2016
6.2 The PBAC noted and welcomed the input from one (1) individual, and one (1) organisation via the Consumer Comments facility on the PBS website. The comments described a range of benefits of treatment with icatibant including the sense of security provided to patients by having the treatment on hand should attacks occur.PSD · Nov 2016
6.29 The sponsor requested a re-negotiation of the current Risk Sharing Arrangement to align with the DUSC utilisation data, the updated treatment algorithm, and the updated economic evaluation. The proposed financial cap is based on the estimates in Section E of the current submission and is higher than the current cap.PSD · Nov 2016
Cost-effectiveness
Minor submission — no economic evaluation required. This is an amendment to an existing listing to limit maximum quantity to 12 injections per script.
The PBAC was of the view that the scenarios used in the utility study are not adequately supported. Further uncertainty arose because attack treatment algorithm variables used in the model are based on the outcomes of trials performed in the hospital setting, the applicability of which to the self-administration setting remains uncertain. Given that the model is driven by the difference between self-administration and best supportive care, the Committee agreed that it is fundamental that there is evidence to support the assumptions about resource use and outcomes in these different settings, that reflects likely usage and outcomes from availability of self-administered icatibant (including differences in timing of treatment, differences in probability of being treated etc). In view of the uncertainties over the economic model the PBAC considered that the already high ICER of between $45,000 and $75,000 per QALY gained was likely to be even higher. PBAC · 2011
Decision context
PopulationAdults with hereditary angioedema due to C1-esterase inhibitor deficiency, assessed to be at significant risk of acute attacks.
Risk sharingRisk sharing arrangement (Deed of Agreement) with financial caps. Previous recommendation was for caps consistent with original listing estimates; November 2016 submission requested increase from $10–$20 million to $30–$60 million over 5 years, which PBAC did not support.
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Jul 2017 | Recommended | — | — | Other |
| Nov 2016 | Not recommended | placebo as proxy for best supportive care (BSC), with delayed use of C1-INH if required | $45k–105k | RCT · Time to onset of relief (TOR) |
| Jul 2011 | Not recommended | best supportive care (BSC) with delayed use of C1-INH concentrate if required | $45k–75k | RCT, Single-arm · Other |
| Jul 2010 | Not recommended | C1-INH concentrate (Berinert®) | — | RCT |
| Jul 2010 | Not recommended | C1-INH (Berinert®) | — | RCT · VAS |
Clinical evidence
| Trial | Phase | N | Primary outcome | Status |
|---|---|---|---|---|
| FAST-3 | Ph 3 | 98 | Time to Onset of Symptom Relief for an Acute Attack, as Assessed by the Patient | completed |
Consumer voice
One individual and HAE Australia provided input describing benefits of icatibant treatment including sense of security, ability to carry out normal daily functions, reduced need for hospitalisation, and minimal side effects.
the sense of security provided to patients by having the treatment on hand should attacks occur Consumer comments · PSD
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC restricts to adults assessed at significant risk of acute attacks; TGA label covers all adults with C1-inhibitor deficiency.