AvacopanTAVNEOS
Treatment of severe active granulomatosis with polyangiitis (GPA) and severe active microscopic polyangiitis (MPA) in combination with rituximab or cyclophosphamide/azathioprine.
Decisions on record
- Meeting Mar 2024 Recommended Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA)
- Meeting Jul 2023 Not recommended Severe active granulomatosis with polyangiitis (GPA) and severe active microscopic polyangiitis (MPA)
Access path
- TGA registered · TAVNEOS
TGA label narrower than the PBS population
- Jul 2023Not recommended
vs glucocorticoids
- ↻ resubmittedMar 2024Recommended · restricted
- PBS listing · Authority Required
From the public summary
Azathioprine scenario Costs $ $244,862 $ lYs 9.21 9 0.2 Incremental cost/extra LY gained $1 Rituximab scenario Costs $ $232,598 $ lYs 9.27 9.15 0.15 Incremental cost/extra LY gained $2 Weighted ICER (50:50): Incremental cost/extra LY gained $3PSD · Mar 2024
Azathioprine scenario Costs $ $244,862 $ QALYs 7.35 6.98 0.37 Incremental cost/extra QALY gained $4 Rituximab scenario Costs $ $244,862 $ QALYs 7.45 7.16 0.29 Incremental cost/extra QALY gained $1 Weighted ICER (50:50): Incremental cost/extra QALY gained $5 Source: Table 3-31, p160 of the resubmission Abbreviations: GC, Glucocorticoids; ICER; Incremental cost-effectiveness ratio; LY, life-year; QALY, quality adjusted life year; SOC, standard of care The …PSD · Mar 2024
The resubmission presented a modelled cost-utility analysis based on the randomised trial (ADVOCATE) directly comparing avacopan + SOC and GC + SOC. The PBAC previously determined that a resubmission for avacopan should be based on the benefits of reducing GC when used as induction therapy (para 7.16, PSD, avacopan, July 2023 PBAC meeting).PSD · Mar 2024
The resubmission argued that statistically significant improvements in renal function in the avacopan-treated arm compared with the prednisone arm were apparent at week 26 (i.e. in the induction phase when patients in the prednisone arm were still on background therapy with rituximab or cyclophosphamide). The resubmission argued improvement persists and remains statistically significant at week 52 and is confirmed as clinically meaningful by clinicians.PSD · Mar 2024
The resubmission described avacopan as superior compared to GC + SOC in terms of both efficacy and safety when administered for a treatment duration not exceeding 52 weeks per severe disease flare. The addition of the 52-week timeframe is the only difference from the previous submission claim.PSD · Mar 2024
The evaluation considered the therapeutic conclusion presented in the resubmission for effectiveness remained inadequately supported. The ESC considered the PBAC’s previous conclusions remain valid: the magnitude of benefit that avacopan + SOC may provide in induction therapy compared to prednisolone + SOC was limited to a potential reduction in GC use with no significant benefit in remission at 26 weeks; the clinical evidence provided was inadequate to …PSD · Mar 2024
The PBAC noted and welcomed the input from individuals (17) and organisations (3) via the Consumer Comments facility on the PBS website. The comments from individuals who have used this medicine for their own health condition described a range of benefits of treatment with avacopan including the ability to halt other treatments (primarily GCs) that had been negatively impacting blood sugar levels, bone density and wound healing.PSD · Mar 2024
The PBAC noted the advice received from the Australian Rheumatology Association and the Australasian Society of Clinical Immunology and Allergy clarifying the likely use of avacopan in clinical practice.PSD · Mar 2024
Cost-effectiveness
The exact ICER value is redacted in the PSD (shown as $ to $ per QALY); numerical values are marked as commercially sensitive.
Decision context
PopulationAdult patients with newly diagnosed or relapsed ANCA-associated vasculitis with severe active GPA or severe active MPA defined as at least one major or three non-major items or at least two renal items of haematuria and proteinuria on the BVAS, receiving concomitant therapy with rituximab (induction/maintenance) or cyclophosphamide (induction)/azathioprine (maintenance).
Why it was knocked back
- Inadequate evidence of comparative benefit for remission at 26 weeks, insufficient evidence for maintenance therapy use from 26-52 weeks, uncertainties regarding additive benefit to rituximab in maintenance phase, limited longer-term safety and efficacy data, clinical claim of superiority not adequately supported for maintenance therapy
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Mar 2024 | Recommended · restricted | glucocorticoids | — | RCT · Induced and sustained disease remission |
| Jul 2023 | Not recommended | glucocorticoids | — | RCT · Remission induction and sustenance |
Clinical evidence
| Trial | Phase | N | Primary outcome | Status |
|---|---|---|---|---|
| ADVOCATE | Ph 3 | 331 | Percentage of Subjects Achieving Disease Remission at Week 26 | completed |
Consumer voice
Consumers reported that avacopan enabled reduction or cessation of glucocorticoid therapy with improvements in blood sugar, bone density, and wound healing, while others emphasized unmet treatment needs for GPA/MPA symptoms and reduced side effects compared to standard care. Professional societies noted potential benefits including delayed relapse, improved kidney function, and better quality of l
the ability to halt other treatments (primarily GCs) that had been negatively impacting blood sugar levels, bone density and wound healing Consumer comments · PSD
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC restricts to severe active disease (BVAS-defined) and first-line use; TGA label permits any active ANCA-associated vasculitis without severity or line restrictions.