Lumacaftor And IvacaftorOrkambi
Treatment of cystic fibrosis patients homozygous for the F508 deletion mutation in the CFTR gene, across multiple age groups (2 years and older).
Decisions on record
- Meeting Jul 2023 Recommended Cystic fibrosis (CF)
- Meeting Jul 2019 Recommended Cystic fibrosis (CF)
Access path
- TGA registered · Orkambi
TGA label equal than the PBS population
- Jul 2017Not recommended
vs best supportive care
- ↻ resubmittedJul 2021Noted
ICER dropped $200,000 → $135,000 (-32%)
- Dec 2021Noted
- PBS listing · Restricted
From the public summary
The PBAC advised the data provided by the sponsor did not meet the requirements of the MAP, and that the long-term benefits of lumacaftor/ivacaftor, in terms of the relative rate of decline in ppFEV and the rate of pulmonary exacerbations, remained 1 uncertain. The PBAC considered additional analyses would be required to meet the requirements of the MAP.PSD · Dec 2021
The PBAC recalled the economic model that informed the recommendation to list lumacaftor/ivacaftor for CF patients over 6 years of age assumed an average change in ppFEV of +3.0% in the first 24 weeks of treatment followed by a relative rate of 1 decline (rROD) of 42% compared to best supportive care (based on Konstan 2017) for the duration of the model. The PBAC noted the rROD calculation was based on a rate 21PSD · Dec 2021
The economic evaluation presented was a cost-utility analysis (CUA). The structure of the model was the same as in the previous (re)submissions (March 2016, November 2016, July 2017, July 2018, July 2019), which presented a CUA of lumacaftor/ivacaftor compared with BSC.PSD · Dec 2021
Based on the pooled estimate of ppFEV rROD from five studies (paragraph 4.19), the 1 submission revised the estimate informing the ppFEV rROD from 42% to 55.7%. The 1 resulting ICER as presented in the submission decreased from $155,000 to < $255,000/QALY gained to $115,000 to < $135,000/QALY gained based on the revised estimate. The PBAC noted the economic model required an estimate of the rROD from week 24 onwards.PSD · Dec 2021
The submission claimed that all available evidence supported the ppFEV rROD 1 exceeding 42% over time for patients treated with lumacaftor/ivacaftor compared to BSC.PSD · Dec 2021
The evaluation considered the therapeutic conclusion presented in the submission may not be adequately supported by the evidence for the following reasons:PSD · Dec 2021
The PBAC noted and welcomed the input from individuals (5) via the Consumer Comments facility on the PBS website. The comments reported the high impact CF has on quality of life and the importance of additional treatment options.PSD · Dec 2021
The submission concluded that in light of its estimate of the rROD at 55.7%, it was appropriate that Option 1 of the MAP be enacted. The PBAC considered that data to reliably inform the rROD beyond 24 weeks was not provided by the submission and hence there was not a basis on which to enact Option 1 of the MAP. For more detail on PBAC’s view, see section 5 PBAC outcome.PSD · Dec 2021
Cost-effectiveness
ICER redacted in public summary; range provided via footnote corresponding to redacted values in MAP table ($115,000 to <$135,000/QALY). Updated from prior submission ($155,000 to <$255,000/QALY).
Decision context
PopulationPatients with cystic fibrosis aged 2 years and older who are homozygous for the F508del mutation in the CFTR gene, and those aged 12 years and older who are homozygous or carry one copy of the F508del mutation with a residual function mutation.
Risk sharingManaged Access Program (MAP) with subsidisation caps for Years 3, 4, and 5, contingent on sustained relative rate of decline in ppFEV₁. Two options apply depending on whether ppFEV₁ relative rate of decline meets or exceeds 42% threshold.
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Dec 2021 | Noted | best supportive care | $115k–135k | Registry · PFS |
| Jul 2021 | Noted | best supportive care | $115k–135k | Registry · Other |
| Jul 2017 | Not recommended | best supportive care | $105k–200k | RCT · ppFEV1 |
Clinical evidence
Consumer voice
Five individuals provided consumer input via the PBS website, reporting the high impact cystic fibrosis has on quality of life and emphasizing the importance of additional treatment options.
The comments reported the high impact CF has on quality of life and the importance of additional treatment options. Consumer comments · PSD
Similar precedents
Regulatory · TGA
Label equal than PBS population — Both TGA and PBAC cover homozygous F508del patients aged 2+ years and heterozygous F508del patients aged 12+ years identically.