SelexipagUPTRAVI
Triple agent sequential add-on therapy with an endothelin receptor antagonist (ERA) and a phosphodiesterase-5 inhibitor (PDE-5i) for patients with World Health Organisation (WHO) Functional Class III or IV pulmonary arterial hypertension (PAH) demonstrating an inadequate clinical response or deterioration whilst on stabilised doses of an ERA and a PDE-5i.
Decisions on record
- Meeting Jul 2020 Recommended Pulmonary arterial hypertension (PAH)
- Meeting Mar 2017 Not recommended Selexipag is indicated for the treatment of idiopathic pulmonary arterial hypertension; heritable pulmonary arterial hypertension; pulmonary arterial hypertension associated with connective tissue disease; pulmonary arterial hypertension associated with congenital heart disease with repaired shunts;
- Meeting Mar 2016 Not recommended Pulmonary arterial hypertension
Access path
- TGA registered · UPTRAVI
TGA label narrower than the PBS population
- Mar 2016Not recommended
vs endothelin receptor antagonists (ERA) and/or…
- Mar 2017Not recommended
Comparator changed: endothelin receptor antagonists (ERA) and/or phosphodiesterase-5…
- ↻ resubmittedJul 2020Recommended · restricted
- PBS listing · Authority Required
From the public summary
The PBAC recommended the Section 85 (General Schedule) - Authority Required (delayed assessment) listing of selexipag for the treatment patients with World Health Organisation (WHO) Functional Class (FC) III or IV pulmonary arterial hypertension (PAH).PSD · Jul 2020
The PBAC noted the views expressed in the sponsor hearing, and the comments from individuals, health care professionals and organisations that outlined the extent to which PAH limits daily activities and impairs quality of life.PSD · Jul 2020
The resubmission presented a new stepped economic evaluation, starting with trial- based incremental cost per progression-free life year, and then implementing a modelled cost-utility analysis. This was appropriate, the March 2016 and March 2017 submissions did not present a cost-utility analysis and the PBAC had considered that a cost-utility analysis would be more informative.PSD · Jul 2020
Table 8 summarises the key components of the economic evaluation. 20PSD · Jul 2020
The resubmission described selexipag as superior in terms of effectiveness and inferior in terms of safety compared with placebo when used as sequential add-on therapy with ERA and a PDE-5i (i.e. triple therapy), for patients with WHO FC III or IV PAH. This claim was unchanged from the previous submissions.PSD · Jul 2020
The ESC considered the claim of superior effectiveness versus placebo in the subgroup of patients matching the PBS eligibility criteria was not adequately supported as: subgroup analyses of patients with WHO FC III PAH on background dual therapy with an ERA and a PDE-5i in GRIPHON did not find a statistically significant 19PSD · Jul 2020
6.2 The PBAC noted and welcomed the input from individuals (33), health care professionals (9) and organisations (4) via the Consumer Comments facility on the PBS website. The comments described some benefits of treatment with selexipag including the convenience of oral rather than intravenous administration, and that it provides an additional treatment option for patients.PSD · Mar 2017
6.41 The sponsor proposed to rebate the Commonwealth of Australia $''''''''''''''' per prescription of selexipag dispensed on the PBS under a formalised Deed of Agreement. The rebate amount was increased compared to the previous submission (when the rebate was $''''''''''''''). 15PSD · Mar 2017
Cost-effectiveness
ICER values are redacted (shown as '''''''''''''') in the public summary document. The document states 'A new a cost utility analysis was presented based on results of GRIPHON trial subgroup with WHO FC III PAH on dual therapy with an ERA and a PDE-5i at baseline. Results presented as costs per QALY gained in the model.' However, the actual numeric ICER is not disclosed.
The listing of selexipag was sought on the basis of cost-effectiveness compared with placebo. PSD · 2017
Decision context
PopulationAdult patients with WHO Functional Class III or IV PAH who have received prior dual therapy with a phosphodiesterase-5 inhibitor (PDE-5i) and an endothelin receptor antagonist (ERA) and are demonstrating inadequate clinical response or deterioration whilst on stabilised doses of both agents.
Risk sharingSpecial Pricing Arrangement (SPA) proposed for all maintenance packs of selexipag as well as the 800 mcg strength initiation pack with a flat pricing structure.
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Jul 2020 | Recommended · restricted | placebo | — | RCT · OS |
| Mar 2017 | Not recommended | placebo | — | RCT · Time to first morbidity or mortality event |
| Mar 2016 | Not recommended | endothelin receptor antagonists (ERA) and/or phosphodiesterase-5 (PDE-5) inhibitors | — | RCT |
Clinical evidence
| Trial | Phase | N | Primary outcome | Status |
|---|---|---|---|---|
| GRIPHON | Ph 3 | 1,156 | Time From Randomization to the First Morbidity Event or Death (All Causes) up to 7 Days Af… | completed |
Consumer voice
Consumer input highlighted the convenience of oral administration compared to intravenous routes and welcomed selexipag as an additional treatment option for PAH patients. Some comments also supported combination therapy for PAH on the PBS.
the convenience of oral rather than intravenous administration Consumer comments · PSD
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC restricts to WHO Class III/IV with prior dual therapy failure; TGA includes Class II and broader treatment-naïve populations.