OsilodrostatIsturisa
Treatment of endogenous Cushing's syndrome in adults who are not candidates for surgery or for whom surgery was not curative.
Decisions on record
- Meeting Sep 2024 Recommended Endogenous Cushing syndrome no PSD
- Meeting Mar 2024 Not recommended Cushing syndrome (CS)
- Meeting Mar 2023 Not recommended Cushing syndrome (CS); adult endogenous CS not suitable for surgery
Access path
- TGA registered · Isturisa
TGA label narrower than the PBS population
- Mar 2023Not recommended
vs placebo, metyrapone, ketoconazole
- Mar 2024Not recommended
Comparator changed: placebo, metyrapone, ketoconazole → Placebo
- ↻ resubmittedSep 2024Recommended · restricted
- PBS listing · Authority Required
From the public summary
7.1 The PBAC did not recommend osilodrostat for the treatment of adult patients with endogenous Cushing’s syndrome (CS) who are not candidates for surgery or for whom surgery was not curative. The PBAC accepted that osilodrostat represented an effective therapy for a disease where high clinical need exists.PSD · Mar 2024
The PBAC advised that additional justification of the cost per responder approach was required, and a resubmission would need to provide a stronger interpretation of the quality-of-life benefit of cortisol control in the short-term (up to one year), medium-term (2−3 years) and long-term (beyond 3 years).PSD · Mar 2024
6.35 The PBAC previously considered that the 12-week trial-based incremental cost per responder analyses in the previous submission did not allow for assessment of cost- effectiveness of long-term use of osilodrostat in this chronic condition (paragraph 7.11, osilodrostat, PSD, March 2023 PBAC meeting).PSD · Mar 2024
6.36 In response, the resubmission presented a stepped cost-utility analysis based on one direct randomised trial, LINC 4, and implementing a modelled evaluation using microsimulation. The resubmission stated that due to the limited available clinical data to model treatment effect, the impacts of comorbidities associated with CS were not considered.PSD · Mar 2024
6.27 The resubmission described osilodrostat as superior in terms of effectiveness compared with placebo and non-inferior in terms of safety compared to placebo. The therapeutic conclusion presented in the resubmission was adequately supported by the evidence.PSD · Mar 2024
6.28 The PBAC had previously considered that despite the limitations of the evidence, it was biologically plausible that if a patient is tolerating and responding to osilodrostat, that the response would be maintained (paragraph 7.9, osilodrostat, PSD, March 2023 PBAC meeting). The economic analysis uses the EOT extension data to support this.PSD · Mar 2024
6.2 The PBAC noted and welcomed the input from individuals (8), health care professionals (6) and organisations (2) via the Consumer Comments facility on the PBS website. The comments described a range of benefits with osilodrostat including high efficacy and safety, improvements in quality of life (including physical, emotional, mental and social wellbeing) and potential survival benefits.PSD · Mar 2024
6.2 The PBAC noted and welcomed the input from individuals (8), health care professionals (6) and organisations (2) via the Consumer Comments facility on the PBS website. The comments described a range of benefits with osilodrostat including high efficacy and safety, improvements in quality of life (including physical, emotional, mental and social wellbeing) and potential survival benefits.PSD · Mar 2024
Cost-effectiveness
ICER not stated in public document. Economic model was considered unsuitable for decision-making by ESC due to failure to incorporate long-term benefits expected with durable cortisol control.
Decision context
PopulationAdult patients with endogenous Cushing's syndrome who are not candidates for surgery or for whom surgery was not curative, with mean urinary free cortisol greater than 1.3 times the upper limit of normal.
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Sep 2024 | Recommended · restricted | placebo | — | RCT |
| Mar 2024 | Not recommended | Placebo | — | RCT · Complete response rate |
| Mar 2023 | Not recommended | placebo, metyrapone, ketoconazole | — | RCT |
Consumer voice
Consumer input from the Executive Director at the World Alliance of Pituitary Organization (WAPO) described the experiences of patients after bilateral adrenalectomy (BLA), highlighting common consequences including lack of energy, anxiety, depression, mobility issues, self-care difficulties, and sleep disturbances that negatively impact patients' social and work life.
The common consequences of BLA included lack of energy which negatively impacts the patients' social and work life as well as anxiety and depression due to social withdrawal, mobility associated tiredness, self-care due to a lack of energy, and sleep disturbances. Consumer comments · PSD
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC restricts to patients not candidates for surgery or with failed surgery, plus specific cortisol threshold; TGA label covers all adults with endogenous Cushing's.