Darbepoetin AlfaAranesp
Not recommended OncologyAuthority RequiredNot applicable line
Treatment of moderate to severe chemotherapy-induced anaemia in patients receiving myelosuppressive chemotherapy for non-myeloid malignancies with haemoglobin level less than 100 g per L.
3
Submissions
3 resub
2007–19
On the record
Redacted
ICER range
commercial-in-confidence
Redacted
Cost basis
Decisions on record
- Meeting Mar 2019 Not recommended DARBEPOETIN ALFA is indicated for: the treatment of anaemia associated with chronic renal failure (CRF). the treatment of
- Meeting Mar 2008 Not recommended Darbepoetin alfa is indicated for the treatment of anaemia associated with chronic renal failure (CRF). Darbepoetin alfa is also indicated for the treatment of anaemia and reduction of transfusion requirements in patients with non-myeloid malignancies where anaemia develops as a result of concomitan no PSD
- Meeting Nov 2007 Not recommended Darbepoetin alfa is indicated for the treatment of anaemia associated with chronic renal failure (CRF). Darbepoetin alfa is also indicated for the treatment of anaemia and reduction of transfusion requirements in patients with non-myeloid malignancies where anaemia develops as a result of concomitan
- Meeting Mar 2003 Recommended Treatment for anaemia associated with chronic renal failure no PSD
Access path
- TGA registered · Aranesp
TGA label narrower than the PBS population
- Nov 2007Not recommended
Uncertain clinical benefit (no statistically significant QoL improvement, no survival benefit, mean Hb difference <1…
- Nov 2007Not recommended
uncertain clinical benefit and resultant uncertain and unacceptable cost-effectiveness; no survival gain, very small…
- Mar 2019Not recommended
Comparator changed: Placebo or no pharmacological treatment → standard medical management…
RecommendedDeferredNot recommended
From the public summary
PBAC outcome
7.1 The PBAC did not recommend the Section 100 (Highly Specialised Drugs Program) Authority Required listing of darbepoetin alfa for the treatment of moderate to severe CIA. This decision was due to an uncertain clinical need and ongoing concerns regarding overall mortality and VTE rates with darbepoetin alfa across the proposed PBS population.PSD · Mar 2019
7.2 The PBAC noted, unlike a RBC transfusion which quickly increases a patients Hb level, darbepoetin alfa gradually increases Hb concentration over a period of weeks. The PBAC agreed with the ESC that the delay in treatment response compared to a RBC transfusion would likely limit the use of darbepoetin alfa in clinical practice. As such, the PBAC considered it unlikely that there was a high clinical need for darbepoetin alfa in CIA.PSD · Mar 2019
Economic analysis
6.40 The resubmission presented a stepped economic evaluation comparing darbepoetin alfa versus standard care. This is the first submission for darbepoetin alfa in which a cost-utility model has been presented. The November 2007 resubmission presented cost-effectiveness analyses with transfusion and haematological outcomes. Table 11 summarises the model structure and rationale as well as steps in the stepped 23PSD · Mar 2019
Outcomes QALYs Methods used to Markov microsimulation model (with results generated using 1000 simulations) generate results Hb levels (one for each of ‘On ESA’ and ‘Off chemo/ESA’ health states) 1. Hb < 80 g/L 2. Hb 80-90 g/L Health states 3. Hb 90-100 g/L 4. Hb 100-110 g/L 5.PSD · Mar 2019
Clinical claim
6.32 The resubmission claimed that darbepoetin alfa was superior in terms of effectiveness compared to placebo (standard medical management). The efficacy conclusions were adequately supported for haemoglobin and transfusion outcomes, however, it was noted that patient-reported outcomes on changes in QoL such as the FACT-F scores did not find darbepoetin alfa to be significantly better than placebo.PSD · Mar 2019
6.33 The resubmission claimed that darbepoetin alfa was non-inferior in terms of safety, overall mortality and PFS, compared to placebo (standard medical management). This claim does not appear to be supported by data presented in the resubmission, pooled results of placebo controlled trials included in this resubmission indicates significantly higher incidence of thromboembolic events for darbepoetin alfa versus placebo.PSD · Mar 2019
Financial management – risk sharing
6.66 No risk sharing arrangements were proposed in this resubmission. For more detail on PBAC’s view, see section 7 PBAC outcome.PSD · Mar 2019
Cost-effectiveness
ICER values are redacted in the public summary document
The PBAC considered that the economic model should have been based on a more patient relevant outcome, preferably QoL. The incremental cost effectiveness ratios were most sensitive to the clinical results for the transfusion incidence and could be in the range of $15,000 - $45,000 (for the population with Hb < 110 g/L) and $105,000 - $200,000 (for the subgroup with Hb < 100 g/L). PBAC · 2007
ICER uncertainEconomic model disputedSurrogate endpoint
Decision context
PopulationPatients with chemotherapy-induced anaemia receiving myelosuppressive chemotherapy for non-myeloid malignancies with haemoglobin level less than 100 g per L
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Mar 2019 | Not recommended | standard medical management (placebo or no pharmacological treatment), includes blood transfusions where clinically indi | — | RCT · Other |
| Nov 2007 | Not recommended | placebo or no pharmacological treatment | — | RCT · transfusion incidence (week 1 to end of treatment period), change in haemoglobin (Hb) from baseline to end of treatment period, survival |
| Nov 2007 | Not recommended | Placebo or no pharmacological treatment | — | RCT · transfusions avoided, Hb change |
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC restricted to moderate-severe anaemia (Hb <100 g/L) and myelosuppressive chemotherapy; TGA label has no severity or chemotherapy-type restrictions.